[House Hearing, 109 Congress]
[From the U.S. Government Publishing Office]



 
                           HUMAN TISSUE SAMPLES:
                           NIH RESEARCH POLICIES 
                               AND PRACTICES


                                  HEARINGS

                                 BEFORE THE

               SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS

                                  OF THE 

                         COMMITTEE ON ENERGY AND 
                                 COMMERCE

                        HOUSE OF REPRESENTATIVES


                       ONE HUNDRED NINTH CONGRESS

                             SECOND SESSION


                        JUNE 13 AND JUNE 14, 2006

                            Serial No. 109-119

      Printed for the use of the Committee on Energy and Commerce



Available via the World Wide Web:  http://www.access.gpo.gov/congress/house


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                   COMMITTEE ON ENERGY AND COMMERCE
                     JOE BARTON, Texas, Chairman
RALPH M. HALL, Texas                      JOHN D. DINGELL, Michigan
MICHAEL BILIRAKIS, Florida                  Ranking Member
  Vice Chairman                           HENRY A. WAXMAN, California
FRED UPTON, Michigan                      EDWARD J. MARKEY, Massachusetts
CLIFF STEARNS, Florida                    RICK BOUCHER, Virginia
PAUL E. GILLMOR, Ohio                     EDOLPHUS TOWNS, New York
NATHAN DEAL, Georgia                      FRANK PALLONE, JR., New Jersey
ED WHITFIELD, Kentucky                    SHERROD BROWN, Ohio
CHARLIE NORWOOD, Georgia                  BART GORDON, Tennessee
BARBARA CUBIN, Wyoming                    BOBBY L. RUSH, Illinois
JOHN SHIMKUS, Illinois                    ANNA G. ESHOO, California
HEATHER WILSON, New Mexico                BART STUPAK, Michigan
JOHN B. SHADEGG, Arizona                  ELIOT L. ENGEL, New York
CHARLES W. "CHIP" PICKERING,  Mississippi ALBERT R. WYNN, Maryland
  Vice Chairman                           GENE GREEN, Texas
VITO FOSSELLA, New York                   TED STRICKLAND, Ohio
ROY BLUNT, Missouri                       DIANA DEGETTE, Colorado
STEVE BUYER, Indiana                      LOIS CAPPS, California
GEORGE RADANOVICH, California             MIKE DOYLE, Pennsylvania
CHARLES F. BASS, New Hampshire            TOM ALLEN, Maine
JOSEPH R. PITTS, Pennsylvania             JIM DAVIS, Florida
MARY BONO, California                     JAN SCHAKOWSKY, Illinois
GREG WALDEN, Oregon                       HILDA L. SOLIS, California
LEE TERRY, Nebraska                       CHARLES A. GONZALEZ, Texas
MIKE FERGUSON, New Jersey                 JAY INSLEE, Washington
MIKE ROGERS, Michigan                     TAMMY BALDWIN, Wisconsin
C.L. "BUTCH" OTTER, Idaho                 MIKE ROSS, Arkansas                       
SUE MYRICK, North Carolina
JOHN SULLIVAN, Oklahoma
TIM MURPHY, Pennsylvania
MICHAEL C. BURGESS, Texas
MARSHA BLACKBURN, Tennessee


                     BUD ALBRIGHT, Staff Director
                    DAVID CAVICKE, General Counsel
    REID P. F. STUNTZ, Minority Staff Director and Chief Counsel


               SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS
                    ED WHITFIELD, Kentucky, Chairman
CLIFF STEARNS, Florida                    BART STUPAK, Michigan
CHARLES W. "CHIP" PICKERING,  Mississippi   Ranking Member
CHARLES F. BASS, New Hampshire            DIANA DEGETTE, Colorado
GREG WALDEN, Oregon                       JAN SCHAKOWSKY, Illinois
MIKE FERGUSON, New Jersey                 JAY INSLEE, Washington
MICHAEL C. BURGESS, Texas                 TAMMY BALDWIN, Wisconsin
MARSHA BLACKBURN, Tennessee               HENRY A. WAXMAN, California
JOE BARTON, Texas                         JOHN D. DINGELL, Michigan
  (EX OFFICIO)                              (EX OFFICIO)                            


                                CONTENTS


                                                                      Page
Hearings held:
        June 13, 2006	                                                1
        June 14, 2006	                                              205
Testimony of:
        Molchan, M.D., Susan, Program Director, AD 
                Neuroimaging Initiative, Neuroscience and 
                Neuropsychology of Aging Program, National 
                Institute on Aging, National Institutes of Health,  
                U.S. Department of Health and Human Services	      167
        Insel, M.D., Thomas R., Director, National Institute of 
                Mental Health, National Institutes of Health, U.S. 
                Department of Health and Human Services	              208
        Friedman, Ph.D., David L.	                              212
        Gottesman, M.D., Michael M., Deputy Director of 
                Intramural Research, National Institutes of Health, 
                U.S. Department of Health and Human Services	      257
Additional material submitted for the record:
        Insel, M.D., Thomas R., Director, National Institute of 
                Mental Health, National Institutes of Health, U.S. 
                Department of Health and Human Services, response 
                for the record	                                      276
        Fitzsimmons, William, Executive Officer, National 
                Institute of Mental Health, National Institutes of 
                Health, U.S. Department of Health and Human 
                Services, response for the record	              279
        Gottesman, M.D., Michael M., Deputy Director of 
                Intramural Research, National Institutes of Health, 
                U.S. Department of Health and Human Services, 
                response for the record	                              284
        Friedman, Ph.D., David L, response for the record	      288

                HUMAN TISSUE SAMPLES:  NIH RESEARCH POLICIES 
                                 AND PRACTICES


                            TUESDAY, JUNE 13, 2006

                           HOUSE OF REPRESENTATIVES,
                       COMMITTEE ON ENERGY AND COMMERCE,
                 SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS,
                                                           Washington, DC.


        The subcommittee met, pursuant to notice, at 2:04 p.m., in 
Room 2123 of the Rayburn House Office Building, Hon. Ed 
Whitfield (Chairman) presiding.
	Members present:  Representatives Stearns, Walden, Burgess, 
Blackburn, Barton (ex officio), Stupak, Baldwin, and Whitfield.
	Staff present:  Mark Paoletta, Chief Counsel for Oversight and 
Investigations; Alan Slobodin, Deputy Chief Counsel for Oversight 
and Investigations; Mike Abraham, Legislative Clerk, Ryan 
Ambrose, Legislative Clerk; John Ford, Minority Counsel; Jessica 
McNiece, Minority Research Assistant; and William Garner, 
Minority Professional Staff Member.
	MR. WHITFIELD.  I would like to call this hearing to order this 
afternoon.  Today and tomorrow, the subcommittee examines the 
important issue of human tissue samples.  These samples, such as 
blood, cells, and spinal fluid are raw material of biomedical 
research that can help improve our healthcare.  These samples 
matter because of their growing importance in biomedical 
research.  Detailed genetic and other biological marker information 
can be derived from these samples and with such information, we 
can dramatically improve the way we diagnose and treat disease.
	The National Institutes of Health is at the forefront in 
collecting these samples and using them for unique medical 
research not conducted in universities or industrial labs.  NIH 
scientists obtain these samples through a great deal of care and 
work with patients and healthy volunteers who participate in 
biomedical experiments.  
	The ability of NIH researchers to obtain samples from people 
and the resources and the freedom to research relies on a basic 
trust.  These hearings focus on whether that trust used to obtain 
human samples for research at NIH is working as well as it should.  
	We look at this important question through the prism of a case 
study.  The study involves Dr. Trey Sunderland of the National 
Institute of Mental Health, and the vials of human spinal fluid and 
plasma he shipped to Pfizer from 1998 to 2004.  Some members of 
the subcommittee may recall Dr. Sunderland's name from the 
subcommittee's June 2004 hearing, where we revealed the 
discrepancies between information provided by Pfizer 
documenting over $500,000 in outside consulting payments to Dr. 
Sunderland over a 5-year period, and the information that was 
given to NIH and to the committee showing no documentation of 
disclosure or approval of these very same outside consulting 
activities for Dr. Sunderland.  NIH has investigated these 
discrepancies and made its determination of multiple violations of 
legal and ethical requirements.
	But today's inquiry is about an investigation beyond those 
compliance issues.  We are concerned primarily about the integrity 
of NIH research.  The committee's concerns in this area were 
prompted in part by Dr. Susan Molchan, who is the Program 
Director for Alzheimer's disease research at the National Institute 
of Aging.  From 1993 to 1995, she conducted a small clinical trial 
involving the collection of spinal fluid from about 25 people, some 
patients with Alzheimer's disease and some normal volunteers, and 
used lithium as a probe for potential biomarkers of Alzheimer's 
disease in spinal fluid and blood.  She had published two papers 
and told the committee staff that she had used, at the very most, 20 
percent of the spinal fluid collected.  The unused spinal fluid 
remains stored in freezers at NIMH geriatric/psychiatric branch.  
The chief of the geriatric/psychiatric branch, Dr. Trey Sutherland, 
assumed control of the spinal fluid and the samples after Dr. 
Molchan left.  
	In the fall of 2004, Dr. Molchan was at the NIA and was trying 
to assist an outside researcher in getting unused samples from Dr. 
Molchan's unfinished study.  Ultimately by March of 2005, she 
learned that Dr. Sunderland was only able to produce a very small 
percent of the unused spinal fluid that remained from her lithium 
study, and that the clinical data from that study had been purged.  
She was concerned about what happened to the more than 95 
percent of the unused spinal fluid samples left in the freezer and to 
the data.
	She pursued her concerns for several weeks during 2005 
through various NIH channels and with the Office of Inspector 
General, Department of Health and Human Services as well.  In 
April 2005, she contacted staff with the Committee on Energy and 
Commerce.  After more preliminary work from the committee 
staff, the bipartisan leadership of the committee and the 
subcommittee started a broad investigation on the issue of human 
tissue samples at the National Institutes of Health and the 
particular case involving Dr. Sunderland and the spinal fluid 
samples.
	The committee has been investigating this issue for over a year 
now.  We have requested records and information.  After 
reviewing the records and interviewing people, the committee staff 
assembled evidence in its report for the subcommittee members.  
The report, which will be placed in the hearing record, raises some 
very troubling questions.  
	Dr. Sunderland is a leading researcher in the area of 
Alzheimer's disease.  For years, he has been interested in finding a 
diagnostic test for this disease.  Pfizer was also interested in this 
goal, and this joint interest was worthy of a scientific collaboration 
between government and the private sector.  In 1998, Dr. 
Sunderland had an opportunity to pursue this project legitimately 
with Pfizer and a British biotechnology firm under existing laws 
and policies that promote this public/private partnership. 
	Instead, disappointingly, the evidence shows that Dr. 
Sunderland used his public office to provide spinal fluid and 
plasma samples to Pfizer at the same time that he engaged in 
personal consulting with Pfizer about these very same samples.  He 
did not disclose these consulting arrangements to NIH; this 
subcommittee exposed them.  And even after he was under 
investigation, the records show that Dr. Sunderland did not 
accurately describe the nature of his consulting activities with 
Pfizer.  According to the records obtained by the committee, Dr. 
Sunderland provided over 3,000 spinal fluid and plasma samples to 
Pfizer and received $285,000 from Pfizer for two different projects 
using these samples.
	Congress and NIH have provided the proper mechanisms for 
government/industry partnership and we encourage it.  Federal 
laws and policies do not permit, however, NIH scientists to profit 
personally from their jobs and their patients by providing 
irreplaceable government assets.  Unfortunately, the evidence 
before us shows Dr. Sunderland operated outside that system.  
Why did he choose to enrich himself?  There were mechanisms 
available to get the resources for his lab as part of this 
collaboration, but there are not records that we have been able to 
find or information showing that this was done, and why not?
	There were mechanisms available to him and NIH scientists to 
obtain patents and royalties.  Dr. Sunderland, however, assigned 
his patent rights to Pfizer under one of the two research projects 
and he was listed as a co-inventor at his home address.  Why didn't 
he tell NIH?  Why didn't he protect the rights of NIH?  And what 
about the Alzheimer's disease patients and human volunteers who 
had their spines punctured and then had to lie on their sides for 
three hours after each procedure?  Did Dr. Sunderland tell them he 
was going to make money from their spinal fluid, and why did he 
make a statement and reaffirm to NIH investigators that his outside 
activities were with one part of Pfizer and that the material transfer 
agreement, his official activities in providing the samples were 
with another part of Pfizer, when the same Pfizer official signed 
the consulting agreement and the material transfer agreement?  
Why did Dr. Sunderland, who has an excellent reputation as a 
researcher and is considered beyond reproach as the Chairman for 
10 years of NIH's Institutional Review Board put himself in the 
position of being under investigation?
	In learning more about the circumstances of Dr. Sunderland's 
conduct, the committee's investigation uncovered other serious 
questions about the adequacy of NIH policy and oversight 
regarding human tissue samples.  For example, Dr. Sunderland 
transferred the human tissue samples taken from subjects for a new 
research purpose without consulting with NIH officials or even the 
Institutional Review Board in charge of protecting these samples.  
Is that a violation of ethical rules, or is that an acceptable practice?  
	From the available evidence, Dr. Sunderland alone, it appears, 
decided to transfer a large number of human tissue samples to 
Pfizer, a company in which he had a financial consulting interest.  
But would Alzheimer's disease research have been better served if 
Dr. Sunderland had consulted with the other NIH experts and 
tested the samples, not just with the technology involved in the 
Pfizer projects, but with other technologies with other companies 
as well?  
	We hope to gain more insight to these matters and improve the 
operations of NIH for the benefit of the American people.  
Already, this investigation has led NIH to revise informed consent 
requirements and has helped stimulate discussions within the 
Institutes to improve policies related to human tissue samples.  
Some of the concerns raised have also led to the Institutes making 
new inquiries about human subject protection and assignment of 
patent rights involved in the Dr. Sunderland matter.  
	Today, we will have one witness, and that is Dr. Susan 
Molchan, who helped raise these concerns over human tissue 
samples, and then tomorrow we will have witnesses from NIH, 
including the Deputy Director of Intramural Research, a former 
Pfizer scientist who worked with Dr. Sunderland, an associate of 
Dr. Sunderland's involved in the Pfizer activities.
	I want to thank Chairman Barton for his support of this 
investigation, and Mr. Dingell and Mr. Stupak for their support, 
and we look forward to Dr. Molchan's testimony.
	[The prepared statement of Hon. Ed Whitfield follows:]

THE PREPARED STATEMENT OF THE HON. ED WHITFIELD, 
CHAIRMAN, SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS

	Today and tomorrow, the Subcommittee examines the 
increasingly important issue of human tissue samples.  These 
samples - such as blood, cells, and spinal fluid - are the raw 
material of biomedical research that can help improve our 
healthcare.  These samples matter because of their growing 
importance in biomedical research.  Detailed genetic and other 
biological marker information can be derived from these samples.  
With such information, we could dramatically improve the way we 
diagnose and treat disease.
	The National Institutes of Health (NIH) is at the forefront in 
collecting these samples and using them for unique medical 
research not conducted in university or industry labs.  NIH 
scientists obtain these samples through a great deal of care and 
work with patients and healthy volunteers who participate in 
biomedical experiments.  The ability of NIH researchers to get 
samples from people and the resources and the freedom to research 
relies on trust.  	These hearings focus on whether that system of 
trust behind the human samples research at NIH is working as well 
as it could.  
        We look at this important question through the prism of a case 
study - an approach this Subcommittee uses often in its oversight 
hearings.  The case study involves Dr. Trey Sunderland of the 
National Institute of Mental Health (NIMH) and the vials of human 
spinal fluid and plasma he shipped to Pfizer from 1998 to 2004.  
Some members of the Subcommittee may recall Dr. Sunderland's 
name from the Subcommittee's June 2004 hearing where we 
revealed the discrepancies between information provided by Pfizer 
documenting over $500,000 in outside consulting payments to Dr. 
Sunderland over a five-year period and the information given by 
NIH to the Committee showing no documentation of disclosure 
and approval of these very same outside consulting activities for 
Dr. Sunderland.
	NIH has investigated these discrepancies and made its 
determination of multiple violations of legal and ethical 
requirements.  But today's inquiry is about an investigation beyond 
these compliance issues. We are concerned about the integrity of 
NIH research.  
        The Committee's concerns in this area were prompted in part 
by Dr. Susan Molchan, Program Director for Alzheimer's Disease 
Research at the National Institute of Aging (NIA).   From 1993 to 
1995, she conducted a small clinical trial involving the collection 
of spinal fluid from about 25 people (some patients with 
Alzheimer's disease and some normal volunteers) and the use of 
lithium as a probe for potential biomarkers of Alzheimer's disease 
in spinal fluid and blood.  In early 1997, Dr. Molchan left the 
NIMH, but she had not finished this study.  She had published two 
papers and told the Committee staff that she had used at the very 
most 20% of the spinal fluid collected.  The unused spinal fluid 
remained stored in freezers at the NIMH Geriatric Psychiatry 
Branch.   The Chief of the Geriatric Psychiatry Branch, Dr. Trey 
Sunderland, assumed control of the spinal fluid samples after Dr. 
Molchan left NIMH.  
        In the fall of 2004 Dr. Molchan was at the NIA and was trying 
to assist an outside researcher in getting unused samples from Dr. 
Molchan's unfinished study held at NIMH.  Ultimately by March 
2005, Dr. Molchan learned that Dr. Sunderland was only able to 
produce a small percent of unused spinal fluid that remained from 
the lithium study and that the clinical data from that study had been 
purged. (SLIDE 4)  She was concerned about what happened to the 
more than 95% of the unused spinal fluid samples left in the 
freezer and to the data.    
        She pursued her concerns for several weeks during March-
April 2005 through various NIH channels and with the Office of 
Inspector General (OIG), Department of Health and Human 
Services (HHS).  In April 2005 she contacted staff with the 
Committee on Energy and Commerce.  After more preliminary 
work from the Committee staff, the bipartisan leadership of the 
Committee and the Subcommittee started a broad investigation on 
the issue of human tissue samples at NIH and the particular case 
study involving Dr. Sunderland and the spinal fluid samples.
	The Committee has been investigating this matter for a year.  
We requested records and information. After reviewing the records 
and interviewing people, the Committee staff assembled evidence 
in its report for the Subcommittee members.  The report - which 
will be placed in the hearing record -- raises some troubling 
questions.
        Dr. Sunderland is a leading researcher in the area of 
Alzheimer's disease.  For years, he had been interested in finding a 
diagnostic test for this disease.  Pfizer was also interested in this 
goal.  This joint interest was worthy of a scientific collaboration 
between government and the private sector.  
        In 1998 Dr. Sunderland had an opportunity to pursue this 
project legitimately with Pfizer and a British biotechnology firm 
under existing laws and policies that promote public-private 
partnerships. Instead, the evidence shows that Dr. Sunderland used 
his public office to provide spinal fluid and plasma samples to 
Pfizer.  At the same time, Dr. Sunderland engaged in personal 
consulting with Pfizer about these very same samples.  He did not 
disclose these consulting arrangements to NIH - this 
Subcommittee exposed them.  Ever after he was under 
investigation, the records show that Dr. Sunderland did not 
accurately describe the nature of his Pfizer consulting activities to 
NIH.  According to the records obtained by the Committee, Dr. 
Sunderland provided over 3,000 spinal fluid and plasma samples to 
Pfizer (SLIDE 5) and received $285,000 from Pfizer for two 
different projects using these samples. (SLIDES 1 and 2) 
        The Congress and NIH have provided the proper mechanisms 
for government-industry partnerships.  Federal laws and policies 
do not permit NIH scientists to profit personally from their jobs 
and their patients by providing irreplaceable government assets.  
Unfortunately, the evidence before us shows Dr. Sunderland 
operated outside that system.  Why did he choose to enrich 
himself?  There were mechanisms available to get resources for his 
lab as part of this collaboration. But there are no records or 
information showing this was done.  Why not?  
        There were mechanisms available to him and NIH scientists to 
get patents and royalties.  Dr. Sunderland, however, assigned his 
patent rights to Pfizer under one of the two research projects and 
he was listed as a co-inventor at his home address.  Why didn't he 
tell NIH? Why didn't he protect the rights of NIH?  What about the 
Alzheimer's disease patients and human volunteers who had their 
spines punctured and then had to lie on their sides for three hours 
afterward?  Did Dr. Sunderland tell them he was going to make 
money from their spinal fluid?  Why did Dr. Sunderland make a 
statement and reaffirm to NIH investigators that his outside 
activities were with one part of Pfizer, and that the material 
transfer agreement, his official activities in providing the samples, 
were with another part of Pfizer when the same Pfizer official 
signed Dr. Sunderland's consulting agreements and the material 
transfer agreement?  Why did Dr. Sunderland - who had an 
excellent reputation as a researcher and was considered beyond 
reproach as the Chairman for 10 years of NIMH's Institutional 
Review Board - put himself in the position of being under 
investigation?
        In learning more about the circumstances of Dr. Sunderland's 
conduct, the Committee's investigation uncovered other serious 
questions about the adequacy of NIH policy and oversight 
regarding human tissue samples.  For example, Dr. Sunderland 
transferred the human tissue samples taken from human subjects 
for a new research purpose without any consultation with NIH 
officials or the Institutional Review Board in charge of protecting 
human subjects.  Is that a violation of ethical rules or acceptable 
practice?  From the available evidence, Dr. Sunderland alone 
decided to transfer a large number of human tissue samples to 
Pfizer, a company in which he had a financial consulting interest.  
But would Alzheimer's disease research have been better served if 
Dr. Sunderland had consulted with other NIH experts and tested 
the samples not just with the technology involved in the Pfizer 
projects but with other technologies with other companies?
	We aim at these hearings to gain more insight into these 
matters and improve the operations of NIH for the benefit of the 
American people.  Already this investigation has led NIH to revise 
informed consent requirements and has helped stimulate 
discussions within NIH to improve policies related to human tissue 
samples.  Some of the concerns raised have also led to NIH 
making new inquiries about human subject protection and 
assignment of patent rights involved in the Dr. Sunderland matter.
Today we will hear from Dr. Susan Molchan who helped raise 
the concerns over human tissue samples.  Tomorrow, we will have 
witnesses from NIH including the Deputy Director for Intramural 
Research, a former Pfizer scientist who worked with Dr. 
Sunderland, an associate of Dr. Sunderland involved in the Pfizer 
activities, and Dr. Sunderland himself.
	I want to thank Chairman Barton for his support of this 
investigation.  I also want to thank Mr. Dingell and Mr. Stupak for 
their support of this investigation.  I also want to note that Pfizer 
was cooperative with the Committee's investigation and we 
appreciate that. 
        I look forward to hearing from the witnesses.

	MR. WHITFIELD.  At this time, I recognize Mr. Stupak.
	MR. STUPAK.  Thank you, Mr. Chairman, and thanks for 
holding this hearing today.  We are going to have another one 
tomorrow.  
	This inquiry has been a bipartisan effort for the past year.  The 
staff report released today provides the committee with a sound 
basis to do our work.  I compliment the bipartisan committee staff 
work and their report.  Through no fault of our staff, I do note that 
this investigation took much longer than should have been 
necessary.  The National Institutes of Health and/or its overseers at 
the Department of Health and Human Services apparently had a 
hard time understanding our bipartisan request letter.  Like other 
initial inquiries from the committee, they originally treated our 
request like a nuisance, something to respond to in a perfunctory 
way.
	For instance, instead of supplying the committee with 
documents showing the disposition of the specific spinal fluid 
samples as requested, NIH gave us unsatisfactory excuses, such as 
possible freezer failure.  We subsequently learned that NIH had 
records of the samples we requested, which were among 3,300 
tubes of fluid samples shipped to Pfizer.  
	In the 2004 conflicts of interest investigation, the 
subcommittee discovered that about 100 NIH scientists failed to 
report income from the 20 drug companies that the committee had 
surveyed.  Pfizer and other drug companies had the records; of 
course, NIH did not.  Fortunately for this investigation, when we 
could not get the records of samples shipped out of the National 
Institute of Mental Health lab, Pfizer again had the records.  I find 
it very disturbing that Pfizer has kept better records than NIH.
	Interestingly, both of these investigations touched on a specific 
National Institute of Mental Health lab chief, Dr. Trey Sunderland.  
Only after this subcommittee provided this information to NIH 2 
years ago did NIH become aware of Dr. Sunderland's receiving 
over $500,000 from Pfizer without reporting it.  Yet, when we 
requested an accounting of the human tissue samples in Dr. 
Sunderland's control, NIH officials apparently accepted his 
explanation that such records did not exist.  This represents a 
complete lack of due diligence and negligence on the part of NIH.  
Unfortunately, the performance of the Department of Health and 
Human Services Inspector General, was similarly lacking.  
Because there is an ongoing inquiry, we will delay the examination 
of the performance of those investigators, but our preliminary 
information is that this IG continues to ignore its first 
responsibility, which is to keep the Department clean.
	Mr. Chairman, the NIH has much to account for today.  
Priceless human tissues samples, samples from a unique collection 
that is not likely to be replicated, even at NIH, were shipped 
without any authority, any oversight, any accountability for a 
private research effort that was evaluated by a single government 
employee.  That employee was Dr. Sunderland, a lab chief who, in 
the end, would pocket $285,000 from his decisions.  We estimate 
that those samples cost NIH over $6 million, and took 15 years to 
collect.
	As you noted, Mr. Chairman, spinal fluid is not easy to obtain.  
It involves three or more hours of inconvenience and often 
considerable pain for each volunteer on each occasion.  People 
volunteered those samples to advance Alzheimer's research, most 
often because they or their loved ones suffered from this disease.  
The volunteers trusted the judgment that NIH would put their 
samples to best use.  Unfortunately, NIH's failure to supervise its 
employees permitted a single scientist to make the judgment to 
give away irreplaceable samples.  The lack of oversight also 
allowed Dr. Sunderland to take some 140 days of travel to perform 
his Pfizer consults.  The failure to demand accountability allowed 
one of the two corroborative research projects to proceed without 
any protection of NIH's right to the resulting data or right to 
intellectual property resulting from the research.  As a result, Pfizer 
owns all research products.
	Of course, NIH didn't know any of this until we asked, because 
they have no uniform audit policy for acquisition, use, and/or 
storage of human tissue samples; storage and protection of data 
generated by their research; determination of whether human 
subject protection and informed consent are assured after any 
specific protocol is ended; accounting for leave of senior 
employees; assuring that the appropriate legal instruments are used 
when human tissues are transferred; or accounting for the fruits of 
corroborative research data and patents.
	Mr. Chairman, it is time to rectify the inadequate oversight that 
has enabled these reckless activities to occur.  Congress entrusts 
NIH with billions of dollars each year.  Biomedical research needs 
to be guided by an unbiased assessment of producing strategies for 
diagnosis or treatment, not whether an NIH researcher maximizes 
his or her personal gain.  Furthermore, thousands of Americans 
entrust NIH with their personal medical histories, tissue samples, 
and other information each year to help find cures for diseases.  
We need to honor their commitment by ensuring that the highest 
scientific standards are upheld.
	Mr. Chairman, I yield back the balance of my time.
	MR. WHITFIELD.  Thank you, Mr. Stupak.  
	At this time, I will recognize the gentleman from Texas, Dr. 
Burgess.
	MR. STUPAK.  Mr. Chairman, if I may, before Dr. Burgess, I 
ask unanimous consent to enter into the record the statement of Mr. 
Dingell, the Ranking Member of this committee.  Thank you.
	[The prepared statement of Hon. John D. Dingell follows:]

THE PREPARED STATEMENT OF THE HON. JOHN D. DINGELL, A 
REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN

        Mr. Chairman, thank you for holding this hearing and initiating 
this bipartisan investigation. This inquiry is an example of how 
productive oversight can be when it is truly bipartisan. And it has 
been bipartisan from the first Chairman's letter to the staff report 
we have before us today. You and Representative Stupak have 
worked together and our staffs have worked together each step of 
the way.
        What have we uncovered? For one thing a number of serious 
deficiencies in individual National Institutes of Health (NIH) 
processes that are enumerated in the staff report. No one looks to 
see if priceless human tissue samples are being put to their best 
use. No one is looking to see if human subject protection rules are 
followed. No one has to account for his or her time or budget. 
        Trusting scientific decisions to the scientists is one thing. 
Giving carte blanche to individual researchers to spend funds and 
divert precious human tissue resources derived from patients under 
their care is quite another. 
        Congress has taken the approach that biomedical research 
decisions are best left to the scientists. This is as it should be. We 
owe it to the taxpayers, however, to ensure that the scientists who 
make decisions regarding very expensive life and death research 
options do so in a rational manner with accountability at least 
within the scientific community. 
        These investigations and the conflict of interest hearings held 
in 2004 have exposed a severe structural weakness in the oversight 
functions within NIH. First it was ethics, now it is something even 
broader. Dr. Zerhouni did a good job tightening up the ethical 
environment after our last set of hearings. I hope Dr. Gottesman 
will undertake a similar clean-up campaign designed to return 
accountability to this great institution.

	MR. BURGESS.  Thank you, Mr. Chairman, and thank you for 
your continued leadership in the investigation that has become 
another very important public health issue.
	During my tenure in Congress, I have had the privilege of 
visiting the National Institutes of Health several times.  After each 
visit, I come away encouraged; encouraged by the research and the 
studies that the scientists perform on a daily basis.  After each visit, 
my hope that a cure for cancer, a cure for Alzheimer's will be 
found, if not during my lifetime, then perhaps during the lifetime 
of my children.
	I would like to take this opportunity to sincerely thank the 
doctors, researchers, and scientists at the National Institutes of 
Health for their dedication to such a noble profession.  It is my 
opinion that outside consulting by scientists is not within itself an 
unethical practice.  While outside consulting is currently prohibited 
by NIH employees, I believe that these types of arrangements can 
be beneficial to society as a whole if constructed in an ethical and 
transparent manner.
	The situation before us involving Dr. Sunderland is an 
egregious example of how the system can fail if there is lack of 
transparency and a lack of ethical behavior.  Dr. Molchan, thank 
you for bringing this situation to our attention.
	In preparation for today's hearing, the committee released a 
bipartisan staff report to the members of this subcommittee.  I 
think it is important to note that the bipartisan staff report came to 
a concluding paragraph, and I am quoting here, "It should be noted 
that the committee staff found no evidence that Pfizer had any 
knowledge relating to the questionable conduct of Dr. Sunderland 
in connection with the April, 1998, material transfer agreement and 
subsequent shipments of samples."  The unethical practice lies 
clearly and solely with Dr. Sunderland.  
	Congress continues our work on reauthorization of the National 
Institutes of Health, a program that spends almost $30 billion a 
year, and it is money well spent.  I feel certain that we can use the 
lessons learned today and tomorrow throughout the reauthorization 
process.  It is our role to provide adequate oversight over the 
National Institutes of Health and ensure that taxpayer dollars and 
other resources, including tissue samples, are used in a worthwhile 
and ethical manner.  We must not abrogate our responsibility to the 
American public regarding this important task.
	Mr. Chairman, again I thank you for holding this hearing, and 
look forward to a lively discussion on the procedures concerning 
human tissue samples.  I will yield back the balance of my time.
	MR. WHITFIELD.  Thank you, Dr. Burgess, and I would, 
without objection, want to enter into the record the staff report on 
this entire issue, as well as those slides and the exhibits.  Without 
objection, so ordered.
	[The information follows:]



                          A STAFF REPORT

          For the Use of the Subcommittee on Oversight and 
                          Investigations
                  In Preparation for Its Hearing,

         "Human Tissue Samples:  NIH Research Policies and 
                    Practices," June 13-14, 2006

        This staff report was written by the Majority and Minority 
Committee staff of the House Committee on Energy and 
Commerce.

Background 
	Human tissues are biological materials defined as "including 
everything from subcellular structures like DNA, to cells, tissue 
(bone, muscle, connective tissue, and skin), organs (e.g., liver, 
bladder, heart, kidney), blood, gametes (sperm and ova), embryos, 
fetal tissue, and waste (urine, feces, sweat, hair and nail clippings, 
shed epithelial cells, placenta)."    For purposes of the 
Subcommittee's inquiry, this report focuses on biological materials 
most frequently used in biomedical research such as tissues and 
cells.  These are raw biological materials extracted from human 
beings that are to be distinguished from the biological inventions 
derived from such samples.  These extracted tissues are stored and 
generate portions of tissues called samples.
	Ever since 1858 when Rudolf Virchow wrote his famous book 
that detailed how changes in cells accounted for diseases in organs, 
human tissue samples have been the foundation of biomedical 
research.   In its 1999 report, the RAND Corporation published a 
"conservative estimate" that more than 307 million tissue samples 
from more than 178 million people were stored in the United 
States.   This number was reportedly increasing by more than 20 
million samples a year.    Tissue samples have played a central role 
in major studies such as the Framingham studies on heart disease 
and the Women's Health Initiative (WHI), one of the largest 
women's health studies in which over a 15-year period, 161,000 
women gave blood, urine, and other samples to investigators.   
Human tissue samples also have significant value to biotechnology 
and pharmaceutical companies because these materials "can help 
them: reduce drug development times; develop new therapies and 
drugs; react quickly to unexpected adverse reactions; and identify 
new assay techniques or biomarkers."  
	The issue of human tissue samples has assumed greater 
importance at the National Institutes of Health (NIH) and 
strengthened the need for more guidance to NIH-funded 
institutions (NIH's extramural research program that are more than 
80 percent of the NIH's budget) as well as for the Institutes and 
Centers at the NIH that conduct their own research (NIH's 
intramural research program).  As noted by the NIH's Director of 
the Office of Science Policy to NIH staff: "[H]uman specimen 
repositories and the use of human specimens and data are 
becoming an increasingly important part of our efforts to advance 
basic science research and translate discoveries into improved 
medical care.  However, the lack of consistency in the regulations, 
policies and procedures governing this type of research is creating 
confusion and barriers for researchers, repository managers, IRB 
[Institutional Review Board] staff, and their institutions.  The 
magnitude of these challenges will likely grow as advances in 
informatics make it possible to make human datasets of 
unprecedented size and scope widely available to the research 
community."   In response to these perceived challenges and as 
part of the NIH Roadmap, the NIH is coordinating "a high priority 
effort to develop trans-NIH policies to govern NIH funded 
research with human specimens and data and to work across 
government to promote more consistent policies in this area." 
	The focus of the inquiry for this hearing is the collection, 
storage, tracking, and use of human tissue samples in the NIH 
intramural research program.  
        The Committee's investigation in this area was prompted in 
part by concerns raised by Susan Molchan, M.D., Program 
Director for Alzheimer's Disease Research at the National Institute 
of Aging (NIA), to Committee staff in April 2005.   Dr. Molchan 
had been a clinical researcher interested in Alzheimer's disease 
research at the National Institute of Mental Health (NIMH).  From 
1993 to 1995, she conducted a small clinical trial involving the 
collection of spinal fluid from about 25 people (some patients with 
Alzheimer's disease and some normal volunteers) and the use of 
lithium as a probe for potential biomarkers of Alzheimer's disease 
in spinal fluid and blood.  In early 1997, Dr. Molchan left the 
NIMH, but she had not finished this study.  She had published two 
papers and used at the very most 20 percent of the spinal fluid 
collected.  The unused spinal fluid remained stored in freezers at 
the NIMH Geriatric Psychiatry Branch.   The Chief of the Geriatric 
Psychiatry Branch was Trey Sunderland, M.D., who assumed 
control of the spinal fluid samples after Dr. Molchan left NIMH.  
        At a hearing on June 22, 2004, the Subcommittee on Oversight 
and Investigations revealed that Dr. Sunderland had received over 
$500,000 in payments from Pfizer during 1999-2004 for outside 
consulting and speaking without any record of prior approval for 
these activities or disclosure in his government financial-report 
filings.  
	By the fall of 2004, Dr. Molchan had been back at the NIH for 
three years, this time at the National Institute of Aging.  At a 
meeting of top scientists and researchers,  she learned that an 
outside researcher was pursuing funding for a lithium study similar 
to the one that Dr. Molchan had been unable to complete at NIMH.  
Spinal fluid samples are extremely valuable and very difficult to 
obtain.  The outside researcher was very interested in getting Dr. 
Molchan's assistance in obtaining the spinal fluid samples and the 
linked clinical data from her study.    Dr. Molchan agreed to assist.   
In the fall of 2004,  Dr. Molchan asked Dr. Sunderland about the 
samples.  After two months of inquiries, Dr. Sunderland sent two 
0.5 cc samples from 10 subjects (about 2-3 percent of the unused 
amount of spinal fluid) to the outside researcher.  In March 2005, 
Dr. Molchan asked Dr. Sunderland about the linked clinical data.  
Dr. Sunderland told her that that the data had been purged because 
it was over 5-7 years old and subject to purging.
	Dr. Molchan was concerned about what happened to the more 
than 95 percent of the unused spinal fluid samples left in the 
freezer and to the data.  In particular, after the public reports about 
Dr. Sunderland's undisclosed activities with Pfizer, she was 
concerned that Dr. Sunderland might have inappropriately or 
improperly diverted spinal fluid samples from her lithium study to 
Pfizer as part of his financial relationship.  She pursued her 
concerns for several weeks during March-April 2005 through 
various NIH channels and with the Office of Inspector General 
(OIG), Department of Health and Human Services (HHS).  In 
April 2005 she contacted staff with the Committee on Energy and 
Commerce.  
	In investigating her concerns and in general about the relevant 
NIH policies, the Committee staff learned from NIH officials that 
NIH had no uniform, centralized, and mandatory authority 
regulating the handling of human tissue samples.  Some NIH 
laboratories kept a written record on the maintenance of these 
samples, but other NIH laboratories did not.  Although there were 
explicit regulations defined in 42 C.F.R. 72.6 detailing the 
handling for hazardous biological materials and select agents, there 
was no explicit policy for the handling and accounting of human 
tissue samples.  In addition, there was no formal inventory control 
or tracking system at NIH.  If a freezer or other storage facility 
malfunctions and the human tissue samples become unusable, NIH 
laboratories were not required to account for the disposition of 
these samples.  There was reason to believe that there were cases 
where NIH lost human tissue samples but had no record of what 
had been lost.  Moreover, the lack of accountability left NIH 
wholly vulnerable to theft and diversion of valuable human tissue 
samples. These preliminary inquiries raised serious concerns over 
what was described to Committee staff by NIH officials as a fairly 
loose, ad-hoc approach to controlling human tissue samples.
        On June 20, 2005, the bipartisan leadership of the full 
Committee and the Subcommittee sent a letter to the Director of 
the NIH requesting records and information on how human tissue 
samples are obtained, stored, tracked, and used in intramural 
programs throughout the institutes and centers of the NIH.    In the 
context of this investigation, the Committee focused primarily on 
spinal fluid samples and blood samples obtained from patients and 
other people participating in NIH intramural clinical trials.
        One subject area of the Committee's June 20, 2005, request 
concerned the disposition of spinal fluid samples from patients 
with Alzheimer's disease and control subjects collected by 
scientists at the National Institute of Mental Health (NIMH) to be 
used in studies involving lithium. After the NIH's August 15, 
2005, production, the Committee staff alerted the NIH that it 
appeared that not all responsive documents concerning these 
samples and Dr. Molchan's lithium study had been provided to the 
Committee.  After the Committee staff raised these concerns with 
NIH about the production, the Committee did receive additional 
responsive records: three sets of records over the last few months 
from the NIH related to the spinal fluid samples and the lithium 
study, with the last set received on January 4, 2006. The 
Committee was troubled that the NIH did not produce all the 
responsive records in the first production, and produced these 
records only after Committee staff pressed several times for these 
additional responsive records.  Most importantly, an NIH 
document received by the Committee in early 2006 documented 
that the Geriatric Psychiatry Branch (GPB) had sent spinal fluid 
samples to Pfizer from 538 subjects, who had participated in 14 
different studies at NIMH.  (See Exhibit 26) The protocol numbers 
listed on the documents showed that spinal fluid had been sent to 
Pfizer from subjects who had participated in Dr. Molchan's lithium 
study.  That fact had not been previously disclosed to either Dr. 
Molchan or to the Committee.
        On January 24, 2006, the bipartisan leadership of the 
Committee and the Subcommittee sent a letter to NIH requesting 
additional records about the disposition of the spinal fluid samples, 
the nature of NIMH oversight over human samples, and the way 
NIH/NIMH handled the Committee's request for records relating 
to the lithium study.  In addition, on January 24, 2006, the 
bipartisan leadership of the Committee and the Subcommittee sent 
a letter to Pfizer, requesting records that could help determine the 
relationship, if any, between the disposition of the spinal fluid 
samples in question and Dr. Sunderland's official and/or private 
consulting activities with Pfizer.  

Methodology
        To review these issues related to human tissue samples, the 
Committee staff conducted extensive interviews with officials 
from NIH, former officials with NIH, officials with Pfizer, former 
officials with Pfizer, and other individuals.   Staff reviewed 
documents obtained by the Committee from NIH and Pfizer.  Staff 
also reviewed public information and records.

NIH's Internal  Investigation
        The NIH's Office of Management Assessment (OMA) 
conducted an internal investigation of Dr. Sunderland's outside 
activity discrepancies first revealed in substantial part at the 
Subcommittee's June 22, 2004, hearing.  The OMA found that Dr. 
Sunderland engaged in serious misconduct, in violation of HHS 
ethics rules and Federal law and regulation.  The OMA confirmed 
that there was no documentation for Dr. Sunderland seeking prior 
approval or reporting the Pfizer activities.  After the revelations of 
the Pfizer activities, Dr. Sunderland self-reported additional 
activities with other drug or biotech companies that lacked 
required documentation in which his payments almost totaled 
$200,000.  Dr. Sunderland claimed that these were paperwork 
violations and that his outside activities did not constitute conflicts 
of interest with his official duties. In particular, Dr. Sunderland 
contended that his outside consulting did not relate to his official 
duty collaboration with Pfizer, which involved the sharing of 
spinal fluid samples under an April 1998 Material Transfer 
Agreement (MTA).  However, the Ethics Review Panel convened 
by NIH in April 2005 found a direct overlap between the subject 
matter of Dr. Sunderland's official area of research and the 
scientific subject matter of his Pfizer consultancies. In addition, the 
Panel expressed concern over the 1998 MTA that Dr. Sunderland 
entered into with Pfizer while he maintained an ongoing consulting 
relationship with the company in the same area.  In addition, in a 
memorandum dated October 12, 2005, the NIH Ethics Panel found 
that Dr. Sunderland's official duties constituted an overlap with 
some of unapproved outside activities with other drug companies 
he self-reported. (Exhibit 35)
        On September 24, 2004, NIH referred an allegation to the 
Office of Inspector General - HHS (OIG) that Dr. Sunderland may 
have conducted outside activities during Government work hours 
without charging leave.  Other records in connection with Dr. 
Sunderland beyond the issue in the referral have also been 
forwarded by NIH to the OIG.  



Committee's Investigation
	It should be noted that the NIH investigated Dr. Sunderland's 
failure to obtain prior approval and disclose outside activities.  
NIH did not investigate the details of the underlying outside 
activities at issue.  The concerns raised about human tissue 
samples led the Committee to investigate issues that arose from Dr. 
Sunderland's transfers of human tissue samples to Pfizer and 
examined the details of Dr. Sunderland's two principal consulting 
arrangements with Pfizer.  This staff report is a preliminary report 
to assist the Members of the Subcommittee on Oversight and 
Investigations in preparing for the hearings to be held on June 13 
and 14, 2006.  

Question One:  Did Dr. Sunderland obtain personal financial 
benefits from outside activities (with no record of disclosure to 
NIH or approval by NIH) with Pfizer, Inc., in any way because 
of actions he took in his official capacity in facilitating the 
transfer to Pfizer of human spinal-fluid samples and plasma 
samples, which were the assets and property of NIH? 

Finding/Supporting Evidence: Yes. Records and interviews 
provide reasonable grounds to believe that Dr. Sunderland 
personally received $285,000 in compensation from Pfizer for 
activities that were derived directly from his official acts in 
providing Pfizer access to spinal fluid samples and plasma samples 
(over 3000 tubes of NIH property and linked clinical data) and that 
Dr. Sunderland used NIH employees and resources to provide such 
access. 

Discussion: 
        The Committee's inquiry focused on the consulting agreements 
involving Dr. Sunderland's collaborations with Pfizer using human 
tissue samples procured from his Geriatric Psychiatry Branch in 
the National Institute of Mental Health (NIMH).  Records from 
Pfizer show that the transfer of spinal fluid samples from Dr. 
Sunderland's branch at NIMH to Pfizer under an April 1998 
Material Transfer Agreement coincided with the initiation of a 
two-year consulting agreement related to Dr. Sunderland's advice 
on information generated from those samples.  The MTA and the 
consulting agreement were part of the same scientific 
collaboration.  This consulting agreement and a spin-off consulting 
agreement from the collaboration netted Dr. Sunderland a 
minimum of $25,000 per year plus $2,500 per day for each one-
day meeting (1998-2003).  According to Pfizer, payments under 
these two contracts totaled $285,000, exclusive of reimbursement 
of travel expenses.   
        Dr. Sunderland had been collecting human tissue samples and 
the related clinical information from NIH Alzheimer's disease 
patients and their families and controls since the early 1980s.  This 
longitudinal collection of spinal fluid and blood samples was 
unique.  While it was possible to purchase spinal fluid samples 
from Alzheimer's disease patients, individuals interviewed by 
Committee confirmed it was unlikely that anywhere but at the 
clinics of NIH could this unique historical collection of human 
tissue samples be assembled.  Dr. Sunderland collected not only 
human tissue samples from Alzheimer's disease patients but also 
samples from their blood relatives as well as samples from 
controls.  
        The longitudinal aspect included in this collection gave the 
samples their unique character.  At least some of the subjects had 
samples drawn both before and after the onset of Alzheimer's 
disease.  Interviews and records obtained from Pfizer provide 
reasonable grounds to believe that obtaining these spinal fluid 
samples together with their clinical histories was a primary reason 
for Pfizer's interest in collaborating with Dr. Sunderland.  
        The samples themselves and the linked clinical data associated 
with these samples are generally considered to be valuable assets 
because such samples can be used for diagnostic, therapeutic, 
research, and commercial purposes.  NIH has told the Committee 
that it takes the position that tissue samples are the property of the 
U.S. Government to the extent that NIH asserts an exclusive right 
to control the disposition and distribution of that material.   That 
would seem to be the case where the NIH has exclusive possession 
and control of the samples through its storage of these materials in 
its freezers in its own buildings, all funded by U.S. taxpayers.  NIH 
continually asserts its ownership interests in such samples through 
its technology transfer policies and legal contracts such as Material 
Transfer Agreements (MTAs) and Cooperative Research and 
Development Agreements (CRADAs).  In addition, the NIH-1884 
form "Request for shipment" used to ship tissue samples to Pfizer 
noted that they were shipments of government-owned property. 
(See Exhibit 22)
        Three legal documents were involved in the transfer of 
invaluable human tissue samples and the collaborative research 
that resulted: a material transfer agreement (MTA) between NIH 
and Pfizer signed by Dr. Trey Sunderland and two consulting 
contracts between Pfizer and Dr. Sunderland.  
        A material transfer agreement is to be distinguished from a 
collaborative research and development agreement (CRADA) and 
a consulting agreement involving the scientist and a company 
independent of the NIH.  In a scientific endeavor such as the 
Pfizer/Sunderland collaboration, according to some NIH officials 
interviewed by Committee staff, a CRADA would have been the 
appropriate legal umbrella for this kind of research.  (This is 
discussed in more detail later in this report.)   Not only would that 
arrangement spell out the contributions and obligations of both 
parties, but it also would spell out the distribution of data and 
intellectual property rights between the government and the private 
sector firm, in this case Pfizer.  Had a CRADA been negotiated, 
Dr. Sunderland would not have been able to receive any outside 
income for his efforts in the collaboration as it would have been 
part of his official duties.  
        Although NIH policies on technology transfer mechanisms 
were evolving and unclear in 1998, according to an NIH official 
interviewed by Committee staff, because the transfer involved a 
commercial entity, it is unlikely Pfizer could have taken possession 
of the samples of this value without a document authorizing the 
transfer.  Absent a CRADA, an MTA was the instrument that 
specified the terms under which the NIH would release human 
tissue samples for a specific research purpose. The MTA did not 
obligate Pfizer to share the resulting data with NIH nor did it 
specify that the government retained any intellectual property right 
to the fruits of the proposed research.  
        Based on its past investigations of NIH scientists' outside 
consulting agreements, Committee staff believes that Pfizer would 
not have entered into a scientific collaboration with Dr. Sunderland 
or any other scientist without a private contract that contained two 
critical clauses: confidentiality and the right of Pfizer to all 
intellectual property created as a result of the collaboration.  
        In a CRADA, Pfizer would not have retained exclusive rights 
to the data or any patents.  Dr. Sunderland would have been 
precluded from any outside income from the collaboration, if there 
had been a CRADA such as the one he had executed with Abbott 
Labs in 1989 in transferring 115 spinal fluid samples. (Exhibit 28)
        In this regard it is important to note that Dr. Sunderland is 
listed as a co-inventor with Pfizer researchers on patents filed in 
Europe and here in the US relating to the April 1998 MTA.  
(Exhibit 29)  Dr. Sunderland executed at least one assignment of 
his patent rights to Pfizer as did his co-inventors as was required 
by his contract of June 10, 1998, and as is typical of discoveries 
made while on a private payroll.  (Exhibit 30)  The United States is 
not an assignee.    
        In 1997 Pfizer entered into a collaboration with a British firm, 
Oxford Glycosciences (OGS), to identify unknown biomarkers that 
would signal the onset of Alzheimer's disease using a proprietary 
OGS proteomics technology.  Dr. David Friedman, the lead Pfizer 
researcher on the project, began courting Dr. Trey Sunderland in 
an attempt to obtain access to the NIH human tissue samples in the 
fall of 1997.  
        In his interview with Committee staff, Dr. Friedman said he 
came to understand the significance of the depth of Dr. 
Sunderland's expertise in his early discussions.  On February 20, 
1998, Dr. Friedman, and three other Pfizer scientists visited 
Sunderland's lab at NIMH.  A Pfizer e-mail documenting the visit 
stated:  "In discussions regarding Pfizer's needs and Sunderland's 
needs, Trey indicated that he was very happy with an MTA 
arrangement plus consulting that Kathy [Smith] has been 
discussing.  Trey was also very interested in publication in a 
reasonable time frame and that he wanted to make sure that 
authorship would be based on scientific and intellectual 
contributions.  We indicated agreement on both matters."
        A month later, at the suggestion of Dr. Sunderland, Kathryn 
Monaghan (now Smith), a Pfizer manager, called Kathy Conn, the 
tech transfer official at NIMH, about using an MTA to transfer 
spinal fluid samples.  Ms. Monaghan believed that this phone call 
reflected NIH's agreement to proceed with the material transfer 
agreement and that they can "work out the CRADA vs. Consult 
part in due course."  (Exhibit 31)
        On April 6, 1998 Kathy Monaghan faxed the final version of 
the MTA to Dr. Sunderland and informed him that the deal with 
OGS had been finalized.  (Exhibit  2)  However, Ms. Conn 
informed the Committee staff that she was unaware that the final 
MTA had been executed.   Records and Committee staff 
interviews of the individuals involved revealed that neither the 
Director of NIMH nor the NIMH Scientific Director, the two 
supervisors of Dr. Sunderland, had knowledge of the transfer of the 
uniquely valuable samples or were informed of the MTA 
negotiations.  On April 8, 1998, Dr. Sunderland signed the MTA to 
transfer coded clinical samples of spinal fluid and the 
accompanying data from over 250 subjects to Pfizer.  Six days 
later, Dr. Barrie Hesp signed the MTA for Pfizer.
        In a letter dated April 20, 1998, Pfizer sent Dr. Sunderland at 
NIH the signed copy of the MTA with a note that indicated that 
they expected the samples to be shipped mid-May (Exhibit 1) Dr.  
Sunderland was then sent a "draft consulting agreement" to his 
home in a letter dated on the same day. (Exhibit 5)  A two-year 
consulting agreement that Pfizer labeled  the "OGS" agreement 
was signed by Dr. Hesp (dated June 10, 1998) and Dr. Sunderland 
(dated June 18, 1998) effective May 1, 1998. (Exhibit 7)  It 
provided for a consulting payment to Dr. Trey Sunderland of 
$25,000 per year and $2,500 per day for each meeting plus 
expenses.  This agreement was renewable for two-year periods, 
and was renewed two more times.  
        It should be noted that this consulting agreement required that 
Dr. Sunderland transfer any interest he may have in the research 
arising from the agreement with Pfizer as he subsequently did with 
the patent assignment.  (Exhibit 7)  Dr. Sunderland also agreed not 
to "disclose confidential information for so long as it remains 
unpublished." 
        Only after the consulting agreement was signed were the 
samples finally shipped from NIH.  According to Dr. Friedman in 
his interview with Committee staff, on or around June 24, 1998, 
Drs. Friedman and Sunderland accompanied 621 tubes to OGS in 
Britain. But Dr. Sunderland did not deliver the clinical data 
associated with the samples until August 1998.  Emails indicate 
Pfizer officials were quite upset about the delay because the 
associated clinical information made these samples useful for the 
intended research and this delay would affect the pace of the 
research. (Exhibit  ). Pfizer calls this research project involving 
NIMH and OGS the "unknown biomarkers" project.  
        By the end of July 1998, Pfizer and Sunderland decided to 
pursue a second collaboration regarding the validity of already 
"known biomarkers," a beta and tau.  (Exhibit 8) The NIH spinal 
fluid samples were to be used for this project as well.  This second 
project resulted in a second separate consulting agreement for Dr. 
Sunderland but not a new MTA for the transfer of NIH samples for 
this separate and new Pfizer research project. The second 
consulting agreement was signed by Dr. Hesp for Pfizer with an 
October 6, 1998, date and by Dr. Sunderland with an October 12, 
1998, date.  On February 9, 1999, the shipment of spinal fluid 
samples from NIH to Pfizer for the "known biomarkers" project 
began.
        According to records and information, approximately 3,200 
tubes of spinal fluid and 388 tubes of plasma were shipped to 
Pfizer in connection with both biomarker projects.  (See Slide 5) 
Of these, 2,200 or so were for the "known biomarkers" project and 
the remaining 1,100 were for the "unknown biomarkers" research.  
The spinal fluid samples linked with the well-characterized clinical 
data are invaluable tools for scientific research.  Based on available 
records, the NIH only had data on the 2,132 tubes shipped in 
connection with the "known biomarkers" project.  The Committee 
staff has reasonable grounds to conclude that NIH did not have 
knowledge of the more than 1,000 tubes of spinal fluid shipped 
pursuant to the "unknown biomarkers" agreement.  

Question Two:  Does the available evidence provide reasonable 
grounds to believe that Dr. Sunderland and others omitted 
important information, or provided inaccurate information, 
about the circumstances surrounding Dr. Sunderland's 
collaborations with Pfizer, Inc. that involved the human 
samples provided by Dr. Sunderland?

Finding/Supporting Evidence:  Yes. While Dr. Sunderland refused 
invitations to be interviewed by the Committee, records and 
interviews provide reasonable grounds to believe that some of Dr. 
Sunderland's statements to the investigators from the Office of 
Management Assessment and communications from Dr. 
Sunderland's attorney to NIH were factually inaccurate or 
incomplete, especially statements relating to the nature of the 
Pfizer collaborations involving human tissue samples.



Discussion:
        The Office of Management Assessment (OMA) of the NIH 
interviewed Dr. Sunderland regarding these matters on August 19, 
2004.  Dr. Sunderland signed the interview notes on August 31, 
2004, confirming with an "X" that "[t]hese notes, with indicated 
changes, accurately summarize the interview." (Exhibit 14)  Dr. 
Sunderland informed OMA that while he had taken the required 
ethics courses and understood there were rules governing 
disclosure of financial interests and approval of outside activities 
"he may not have paid proper attention" to such matters in the past.  
He maintained that he did provide the documents from which to 
complete the 520s (outside activity request forms) but that 
somehow the clerical staff did not make the necessary submissions 
nor did they inform him that such submissions were not made. 
 	With regard to his financial disclosure forms, Dr. Sunderland 
placed blame for at least part of their inaccuracy on his support 
staff.  The OMA dismissed this argument:  "Dr. Sunderland 
violated NIH and Commissioned Corps procedures and policies on 
multiple occasions (Pfizer reported 140 activities for which there 
were no approvals) all of which cannot be dismissed as 
administrative oversights or anomalies. Given that he 
acknowledges that he had concerns about administrative support, 
he should have ensured that forms were submitted to the NIMH 
ethics office and that approvals were given. Dr. Sunderland was 
aware of the NIH ethics process through ethics training and was 
ultimately responsible for ensuring that all activities were approved 
and all financial disclosures were made." (See Exhibit 32)  
Committee staff interviewed several individuals within the 
Geriatric Psychiatry Branch run by Dr. Sunderland and found no 
support for his position regarding clerical malfeasance.
        When asked about his consulting conflicts of interest, Dr. 
Sunderland told OMA that "he had a consulting arrangement with 
Pfizer Corporate and the MTA with Pfizer researchers."  In fact, 
not only was the MTA and his initial consulting agreements signed 
by the same Pfizer official, Dr. Barrie Hesp, both contracts covered 
work directly related to the samples initially supplied under the 
MTA.  (Exhibit 13) 
        Dr. Sunderland further claimed that he sent human spinal fluid 
samples to Pfizer as he had to more than 30 other collaborators and 
that his collaboration with Pfizer would not have required visits to 
the company, as this was "an exchange of material for analytical 
data."   In fact, records show that Dr. Sunderland and his associate 
Karen Putnam visited the Pfizer facilities on a number of occasions 
to work on the data and, according to Dr. Friedman, at least once 
Dr. Sunderland accompanied Friedman and the spinal fluid 
samples on a plane to OGS in England.  In addition to the 
Friedman interview information and several e-mails discussing 
trips to Pfizer in relation to the unknown biomarker work, both 
Karen Putnam and Pfizer informed Committee staff that Pfizer 
considered the primary data associated with the unknown 
biomarker project to be proprietary and could only be accessed on 
Pfizer property.  (Exhibit 33)
        Another inconsistency with the relevant documents and the 
information conveyed by Pfizer regarding Dr. Sunderland's 
consulting activities was Dr. Sunderland's statement in the OMA 
interview that "his consulting work with Pfizer has to do with drug 
development and lectures."  Certainly lectures to audiences of 
doctors arranged by Pfizer's marketing team charged with 
promoting Aricept accounted for substantial payments to Dr. 
Sunderland ($311,150 from 1996 to 2004 according to Pfizer)  
(Exhibit  34)  The consulting work involving the human tissue 
samples, however, was separate and apart from those lectures.  
(Exhibit 34)  To the extent Dr. Sunderland meant that his "drug 
development" consulting was drug-specific, except perhaps for 
participation on various Pfizer-sponsored Advisory Boards relating 
to marketing strategy, Committee staff found little evidence from 
records or interviews that Dr. Sunderland's consulting with Pfizer 
was related to any existing drug or drug under development.  On 
the other hand, if Dr. Sunderland meant that his "drug 
development" consulting in a more general way applying to 
strategic advice to classes of medications, his attorney in a 
December 8, 2004, letter to NIH distinguished this general 
consulting from his work on the "unknown biomarkers" project:  
"Generating new approaches to shorten the duration of clinical 
trials using various target markers is an obvious priority for 
companies like Pfizer, and Dr. Sunderland provided ongoing 
consultation about the development of such strategies.  This 
consulting is quite different and separate from the exploration of 
peptide biomarkers for possible diagnostic and prognostic use in 
Alzheimer's disease."   (Emphasis added).  Later in the same 
letter, Dr. Sunderland's attorney described a reason for the April 
1998 MTA collaboration as "[p]roteomic exploration of CSF 
[cerebrospinal fluid] was designed to help discover peptide targets 
for drug development with both scientific and potential 
commercial applications."  (Emphasis added). 
        During much of the time period (1998-2004) of Dr. 
Sunderland's consulting with Pfizer, Ms. Karen Putnam was a 32-
hour per week employee of NIMH assigned to Dr. Sunderland's 
branch, although she was telecommuting from the University of 
Cincinnati where she was pursuing a graduate degree. (See Exhibit 
11)  According to e-mails, Dr. Sunderland urged Pfizer to hire Ms. 
Putnam to administer the database related to the unknown 
biomarker project.  Pfizer tightly held the data from this 
"collaboration" so her work on that database had to be done at the 
company.  Ms. Putnam performed a similar function with regard to 
the "known biomarkers" database.  She informed the Committee 
staff that she understood that while the "unknown biomarkers" 
project was covered by her consulting agreement with Pfizer, the 
work she and Dr. Sunderland did with Pfizer on known biomarkers 
was a part of her official duties.  Both biomarker projects started 
with consulting contracts between Pfizer and Dr. Sunderland, not 
independently and solely from NIH. 
        During his OMA interview Dr. Sunderland was asked whether 
he told Karen Putnam that she did not have to seek approval for 
her work with him at Pfizer.  In the signed interview notes Dr. 
Sunderland claimed not to remember if he told Ms. Putnam not to 
file, but he went on to state that he did not think she had to because 
she was a part-time employee on an IPA and because "her duties 
did not overlap with any decisions regarding drug or protocol 
development."  Ms. Putnam was a direct report to Dr. Sunderland 
and had received almost $65,000 in consulting fees and expenses 
from Pfizer to manage the data of the unknown biomarker study. 
(Exhibit 39).  OMA found, and Ms. Putnam confirmed, that she 
had not submitted requests for outside activities.  Exhibit 11.  In 
addition, the NIH ethics review panel concluded that had Karen 
Putnam filed a request for outside activity the request would have 
been denied because it related to her official duties.  (Exhibit 27)  
OMA noted in its review of Karen Putnam's outside activities that 
in an e-mail to Ms. Putnam, dated June 18, 2004, the NIMH Ethics 
Coordinator stated that Dr. Sunderland had called from abroad to 
say that he had advised Ms. Putnam that she did not have to file for 
prior approval.
        Dr. Sunderland's attorney in an August 31, 2004, letter to 
OMA stated:  "There was no conflict between his 
consulting/lecturing and his clinical work at the NIH.  . . "[He] 
never hid that relationship; and that there never was a conflict of 
interest - in any respect whatsoever - between his NIH work and 
what he did as a consultant and speaker for Pfizer.  . . . The 
relevant facts are now before the NIH in their entirety."  The NIH 
Ethics Review Panel specifically found that there was "a direct 
overlap between the subject matter of Dr. Sunderland's official 
area of research and the scientific subject matter of his Pfizer 
consultancies." (Exhibit 35)  He would not have been "given prior 
approval for the consultant activities."  The Ethics Panel 
"expressed further concern over the Material Transfer Agreement 
(MTA) that Dr. Sunderland entered into with Pfizer in 1998 while 
he maintained an ongoing consulting relationship with the 
company in the same area." Based on records and interviews, 
Committee staff believes that NIH did not conduct interviews with 
Pfizer employees nor obtain from Pfizer the underlying records of 
Dr. Sunderland's consulting agreements.  Thus, even without the 
Pfizer documents and interviews that show connections between 
the MTA and the consulting, the Ethics Review Panel still 
concluded in April 2005 that there was a conflict of interest. 
        Moreover, OMA believed that Dr. Sunderland did much of the 
Pfizer-paid work on government time.  Dr. Sunderland 
acknowledged in the OMA interview that he never kept track of 
his leave time nor, as her supervisor at NIH, did he check to see if 
Ms. Putnam had taken leave when he signed her time cards.  
	Records and interviews also raised questions about Dr. 
Sunderland's openness about the "unknown biomarkers" 
consulting agreement involving a third-party British company 
called OGS.  For example, in her June 9, 1998, e-mail, Kathryn 
Smith noted to other Pfizer officers:  "For your information, Dr. 
Trey Sunderland at NIH (our source for the AD samples) has 
requested that we do not mention him in any publicity concerning 
his involvement in our OGS collaboration." (Exhibit 23).  In 
addition, when the Committee first raised questions about the 
discrepancies involving Dr. Sunderland's outside activities with 
Pfizer, the NIMH ethics coordinator in a June 18, 2004 e-mail to 
Dr. Sunderland asked directly: "There is a record of an MTA 
agreement with Pfizer signed 4/98.  Could payments have related 
to that?" (Exhibit 16)  Based on records and interviews, there is no 
evidence that Dr. Sunderland responded to this question.  It should 
also be noted that the terms of Dr. Sunderland's consulting 
agreements state: "Pfizer agrees that it will not make public this 
agreement nor the terms associated with it."  
        Dr. Trey Sunderland is still an employee at the NIMH and is a 
member of Public Health Service Commissioned Corps.  
Administrative action rests with the Corps and not NIH per se.  Dr. 
Thomas Insel, the Director of NIMH, forwarded a summary of the 
OMA findings and those of the Ethics Panel to the Commissioned 
Corps, noting that he was informed that civilian employees guilty 
of the same violations would be proposed for removal. In relevant 
part that document states:
        "Dr. Sunderland placed the NIH in a position where it had 
        to respond to allegations of impropriety, which 
        compromised faith in the Agency and trust in our research.
        Dr. Sunderland violated ethics rules with regard to his 
        relationship with Pfizer and engaged in relationships with 
        Pfizer and many other organizations that would not have 
        been approved had he submitted them for approval in 
        accordance with the process for seeking approval of outside 
        activities...Not disclosing over $500,000 in income was not 
        an oversight or lapse in judgment but appears to be a 
        deliberate decision not to comply with the rules, policies 
        and procedures that are necessary to protect the NIH, its 
        scientists and most importantly, its science." 

Question Three:  Did the Committee's investigation of the 
circumstances surrounding Dr. Sunderland's transfer of 
human samples to Pfizer identify evidence that raised other 
compliance issues and policy questions?

Finding/ Supporting Evidence:  Yes.  The investigation found 
reasonable grounds to believe there was questionable compliance 
with human subject protection and NIH technology transfer 
policies that existed at the time.  The evidence also raised 
regulatory and ethical questions that are pertinent to NIH's 
consideration of current policy related to human tissue samples.



Discussion:  
Human subject protection  
        A human subject is a living individual about whom a 
researcher (called an investigator) obtains either (1) data through 
intervention or interaction with the individual, or (2) identifiable 
private information.  In the case study before the Subcommittee, 
Dr. Sunderland and other researchers collected spinal fluid by 
injecting the human subject with a needle at the base of the spine 
in a procedure called lumbar puncture (LP).  According to the 
informed consent language in several of the protocols involved, 
this procedure is conducted in the morning, after the subject has 
had a night of bedrest.  The subject lies on one side, the subject's 
lower back is cleaned with antiseptic, and a local anesthetic such as 
novocaine is injected in order to temporarily numb a small area of 
skin.  A needle is then placed into the spinal fluid sac, allowing an 
ounce of spinal fluid to drip into collection tubes.  The needle is 
then removed and the subject is asked to lie on her/his abdomen for 
three hours to reduce the likelihood of developing a headache after 
this procedure.  The LP procedure only takes 5-15 minutes.  Most 
subjects experience only minor or moderate pain, similar to that 
experienced when an injection is received.
        The spinal fluid samples, usually collected in 20-30 cc 
amounts, are then alliquotted or subdivided into ten smaller tubes.  
Some small subset of the total amount is then used for the research 
study, with several other vials or test tubes of fluid left over, 
unused, stored in -70 degree centigrade freezers.
        Researchers at the NIH are responsible for protecting the rights 
and welfare of the human subjects who participate in their 
research.  All intramural researchers at the NIH are responsible for 
knowing whether or not their research involves human subjects.  
Thus, legal obligations to protect human subjects apply to human 
tissue samples and private information, such as medical 
information, that can be readily identified with individuals.
        a. Questionable handling of informed consent.  One issue 
presented by this matter involves the adequacy of informed 
consent for new, future uses of leftover human samples.  The 
ethical foundation for informed consent is the principle of respect 
for persons, which requires that research subjects be given the 
opportunity to choose what shall and shall not happen to them.   
Valid informed consent requires disclosure of relevant information 
about the research, comprehension of the information by the 
prospective subject, and his or her voluntary agreement, free of 
coercion and undue influence, to participation. 
 	In this case, Dr. Sunderland transferred spinal fluid samples to 
Pfizer that were collected from subjects whom most were told of 
the specific purpose of the particular research study being 
conducted, but not about the research purpose of the Pfizer 
collaboration, because in many cases that collaboration had not yet 
even been developed.  At the time of collection, many of the spinal 
fluid samples were not obtained for the research purpose of the 
Pfizer collaboration.  In general, there is a question about whether 
most of the protocols at issue had adequate informed consent 
language about consenting for future research uses of leftover 
samples.  A few of the protocols involving the subjects are still 
ongoing and Dr. Sunderland actually sought Institutional Review 
Board (IRB) approval for amending these ongoing protocols to 
reflect the new research purpose involving Pfizer. 
        Human subject protection regulations, however, state that 
unless the samples are anonymized and not linked to identifiable 
patients, the human tissue samples are not exempt from IRB 
review and some independent review (either from the IRB or the 
human subjects protection office of the institute or center) must be 
conducted to determine if full IRB review is needed and if so, 
whether the subjects need to be consented again for the new use.   
With respect to the samples transferred to Pfizer, NIH reported to 
Committee staff by e-mail that "[n]either the NIH OHSR [Office 
of Human Subjects Research] nor the NIMH [Institutional Review 
Board] have records documenting a review of the transfer to 
Pfizer."  According to NIH, "Dr. Sunderland has advised NIH that 
he believed at the time of the transfer that use of specimens in his 
collaboration with Pfizer, as described in the 1998 MTA, was 
completely consistent with both the protocols in which those 
samples were obtained, and the informed consent documents 
signed by participants."  
        But was it Dr. Sunderland's judgment alone to determine 
whether the use of the samples was consistent with the protocols?  
Under the April 1995 Guidelines for the Conduct of Research 
Involving Human Subjects in effect at the time of the 1998 
transfer, the use of human tissue samples were exempt from the 
NIH requirements on human research protection if the sources of 
pathological specimens "cannot be identified directly or through 
identifiers linked to the subjects." The Guidelines also state in 
bolded print: "Investigators should not make determinations about 
exemptions without consulting OHSR."
        The terms of 1998 Material Transfer Agreement (Exhibits 2 
and 3) and the records produced by Pfizer relating to the samples 
provide reasonable grounds to believe that Dr. Sunderland 
intended to transfer, and actually transferred, coded clinical 
samples to Pfizer.   Coded clinical samples are specimens supplied 
with a code rather than a name or social security number.  Because 
these samples remain linked through codes to identifiable subjects, 
questions are raised over whether these samples would have been 
covered by human subject protection guidelines and whether Dr. 
Sunderland should have sought an independent consultation or 
determination.   Currently, in light of concerns raised by the 
Committee's investigation and at the direction of the NIH Deputy 
Director for Intramural Research, an NIH investigation is being 
conducted to determine if Dr. Sunderland violated any regulatory 
or ethical standards in transferring spinal fluid samples to Pfizer 
without any IRB review from protocols that did not cover the 
research purpose in the Pfizer biomarker projects.	
        b. Inadvertent disclosure of subject names and other 
privacy information.  In reviewing records produced by Pfizer, 
Committee staff found that February-March 1999 spreadsheet 
records for assays of two different potential biomarkers in 1999 
contained the names of approximately 120 subjects who were the 
sources of the biological material, along with their codenames, 
NIH ID numbers, dates of birth, race, and sex.  In consultation with 
Pfizer's outside counsel, Committee staff confirmed that these 
records did indeed represent an inadvertent disclosure of subject 
names.  According to Pfizer's outside counsel in a March 31, 2006, 
letter to Committee staff, the spreadsheets contained information 
transcribed by Pfizer from labels on the vials sent by the NIMH.  
The samples were subsequently coded by Pfizer for analysis using 
the first three letters of the patient's last name followed by the first 
three letters of the first name.  The results of the 
study were included in the April 23, 2003, article in the Journal of 
American Medical Association as well as the analysis of a later set 
of samples.  Subsequent samples arrived from the NIMH pre-
coded using a numerical coding system. 
        In response to the Committee staff's question about Pfizer's 
handling of this inadvertent disclosure, Pfizer's outside counsel 
wrote:

	"At the time that the NIH disclosure occurred, the Health 
Insurance Portability and Accountability Act (HIPAA), which 
established requirements regarding the use and disclosure of 
Protected Health Information, was not yet in effect, and thus there 
was no legal obligation imposed upon Pfizer to return or reject the 
information received.  Even under the current HIPAA 
requirements, Pfizer's research and development organization is 
not a 'covered entity,' and the duties imposed on such persons 
inadvertently receiving protected information are not clear.  
However, we believe Pfizer handled the inadvertent disclosure 
appropriately by creating an [sic] code to de-identify patients in the 
course of the research effort." 

	There is no evidence that Pfizer contacted NIH about the 
inadvertent disclosure.  There is no evidence that NIMH was aware 
of the inadvertent disclosure.  If that was the case, NIH had no 
information to determine what led to the inadvertent disclosure, 
and was not in a position to correct a possibly recurring, systemic 
problem that increases the risk of inadvertent disclosure of privacy 
information.  Further investigation would be needed to determine 
the circumstances that led to the inadvertent disclosure.
	Committee staff understands from a discussion with NIH 
Acting Director for Human Research Protection that the release of 
patient names, whether accidental or not, is not consistent with 
NIH research standards and any manuscript in connection with the 
affected research project might not be published.  This would need 
to be reported to the IRB, and to the NIH Deputy Director for 
Intramural Research.  The NIH Deputy Director in turn might 
report this disclosure to the Office of Human Research Protection.  
	c. Questionable non-disclosure of financial relationship to 
IRB.  As part of his financial arrangement with Pfizer, Dr. 
Sunderland transferred spinal fluid samples to Pfizer from 1998 to 
2004 for which he was paid $285,000 to advise Pfizer on data 
relating to the samples provided.  According to NIH records, Dr. 
Sunderland provided spinal fluid samples that had been collected 
from 14 different studies.  Two of these studies were initiated in 
2001 and 2002, respectively.  In other words, Dr. Sunderland was 
performing lumbar punctures for spinal fluid at a time Pfizer 
wanted spinal fluid samples, and at a time Dr. Sunderland sought 
and received monetary compensation for his efforts to assist Pfizer 
in interpreting data generated from these spinal fluid samples he 
provided.  In addition, while other studies no longer involved 
active collection of spinal fluid, these studies were still ongoing 
and were subject to continuing review by the NIMH IRB.  As part 
of this continuing review process, Dr. Sunderland as the 
accountable investigator on the study had to check off "yes" or 
"no" responses to a series of questions on the NIH-1195 form, 
Clinical Research Protocol Continuing Review Application.  The 
last question on the form was: "Have any investigators developed 
an equity or consultative relationship with a non-NIH source 
related to this protocol which might be considered a conflict of 
interest?"  According to all forms related to spinal fluid protocols 
signed by Dr. Sunderland during the time he was consulting with 
Pfizer, the "no" box response was checked. (Exhibit 24) 
	Committee staff did not receive any records that linked the 
individual samples provided to Pfizer to specific protocol numbers.  
The 2001 study and the 2002 study, however, were identified as 
sources of spinal fluid samples to Pfizer.  (Exhibit 26)  Thus, while 
the Committee staff does not believe it has records linking the 
protocol number to a particular NIMH shipment to Pfizer, samples 
were provided to Pfizer from these studies in one of those years in 
which Dr. Sunderland represented to the IRB that he (or any other 
investigator associated with the study) had no outside financial 
interests related to the protocol.
        d. Cancellation of lithium study without notice to subjects.  
Dr. Molchan left NIMH in early 1997.  By that time, Dr. Molchan 
had completed the spinal fluid collection phase of the lithium study 
a few years earlier.  She was still, however, conducting the study 
and had used only a relatively small percentage of the samples.
	Committee staff understands that sometimes when an NIH 
scientist in charge of a human subjects study leaves NIH, another 
NIH scientist is assigned to take charge of the study and the study 
is continued.   When Dr. Molchan left NIMH, there was reason to 
believe (IRB approval, two papers published) the lithium study 
would be continued and that Dr. Sunderland as Branch Chief 
would either take over the study or assign someone to take over the 
study.  Instead, the study was discontinued.  Committee staff has 
asked NIH why the study was discontinued.  To date, NIH has not 
provided a response on why this study was discontinued.
	Committee staff has not found any evidence that the subjects in 
the lithium study were notified about the termination of a study.  In 
these cases, where a clinical trial is terminated, the question is 
raised whether the subjects in that study should be notified of the 
termination.  It is unclear how common it is for the written 
protocols of the clinical trial to include provisions about 
termination and notification.  On the question of when a subject 
should be notified about termination of a study, an NIH official 
with expertise on human subjects protection told Committee staff 
that she believed that it depended on whether the study followed 
the subjects over a period of time. Nevertheless, the NIH Office of 
Intramural Research is working on a computer consent prototype 
and whether it should be a standard requirement to inform subjects 
of a study's termination.



Technology Transfer Issues
        In pursuing its mission, NIH scientists often discover new 
technologies.  The process of sharing these new technologies with 
other organizations and the public is called technology transfer.  
For example, the sharing of new research materials with 
colleagues, the pursuit of collaborative relationships with outside 
entities, and the awarding of intellectual property rights to 
commercial entities for development and commercialization, are 
all considered technology transfer activities.   The NIH Office of 
Technology Transfer is responsible for developing and 
implementing technology transfer policies at NIH.  Each Institute 
has a technology transfer office that monitors, evaluates, and 
manages the Institute's invention portfolio.  These offices review 
Employee Invention Reports (EIRs) and negotiate transactional 
agreements between the Institute and outside parties, including 
other Federal laboratories, State and local governments, 
universities, and pharmaceutical and biotechnology companies.  
Among these agreements are Material Transfer Agreements 
(MTAs) for the exchange of research materials, and Cooperative 
Research and Developments Agreements (CRADAs) for 
collaborative research endeavors.  
        In this case, questions are raised in a number of areas about 
how NIMH at the time implemented technology transfer policies 
and the adequacy of certain technology transfer policies.
        a.  Improperly authorized transfer.  The transfer of spinal 
fluid samples was facilitated by the April 1998 Material Transfer 
Agreement between NIMH and Pfizer. The Committee's 
investigation found two versions of the executed MTA.  One 
version contained the signature of Dr. Sunderland as the provider 
of the samples on behalf of NIMH and the signatory for Pfizer, Dr. 
Barrie Hesp. (Exhibit 3)  This is the only version of the MTA that 
Pfizer told the Committee staff it has. Committee staff found no 
evidence that Pfizer had any other version of the MTA.  According 
to a Pfizer manager involved with the MTA, Pfizer made an effort 
to confirm that Dr. Sunderland had the authority.   A March 1998 
Pfizer e-mail does substantiate phone contact between the Pfizer 
manager and the NIMH technology transfer director about the 
MTA.    Although she did not have specific recollection about the 
Pfizer phone call, the NIMH technology transfer director at the 
time (who has since left the NIH) told the Committee staff that she 
recalled getting phone calls about MTAs.  These would not have 
been calls to receive official clearance but just preliminary 
inquiries.  These kinds of calls were not documented.  According 
to the official, she believed the Pfizer inquiry would have been 
about what form to use in transferring samples to Pfizer.  She did 
not know that Dr. Sunderland and Pfizer were executing the MTA 
immediately.  She expected to see the MTA and review it.  There 
is, however, no evidence showing she received any Pfizer 
correspondence and was sent the MTA.  She had no recollection 
about any mention of possible consulting, but even if it had been 
mentioned, she would have expected the ethics office to be 
involved in that review.  The official disputes that she confirmed 
that Dr. Sunderland was authorized to execute the agreement. 
Based on the phone call, the official expected to review the MTA 
and forward it to the NIMH Scientific Director for signature.  The 
official's recollection was that all transfers of human tissue 
samples to researchers outside NIH were documented through 
MTAs.
        In early 1999 during an office move, the NIMH technology 
transfer office staff discovered a number of MTAs that had not 
been co-signed by the NIMH Scientific Director, as required by the 
written delegations of authority in effect at the time.  One of these 
MTAs was the Sunderland-Pfizer MTA.  When these MTAs were 
brought to his attention, the NIMH Scientific Director co-signed.  
He co-signed the Pfizer MTA on February 24, 1999.  At that time, 
NIMH had already made three shipments of spinal fluid to Pfizer.  
(Exhibit 3, p.3) The co-signed MTA was retained in NIMH files.  
According to NIH, there was no evidence that Dr. Sunderland was 
given a copy of the 1998 MTA after Dr. Desimone signed, and Dr. 
Sunderland told NIMH he did not get a copy of the co-signed 
MTA until about several months ago when he requested it from the 
NIMH Executive Officer.   Moreover, it is unknown when Dr. 
Sunderland learned about the existence of the co-signed MTA.
        The available evidence shows that Pfizer only had the MTA 
with Dr. Sunderland's signature.  Under NIMH policy at the time, 
however, Dr. Sunderland was not the authorized signatory to 
execute the MTA.  Questions arise about whether NIMH's transfer 
of samples was legally authorized and the legal implications for 
NIH.  Furthermore, available evidence shows that NIMH 
management did not provide the co-signed versions to either Dr. 
Sunderland or Pfizer.  This is of concern because NIMH 
management should have an interest in correcting an internal 
problem of unauthorized or improperly authorized material 
transfers.  The problem cannot be corrected if management does 
not make NIH scientists aware of the error.  In a conversation with 
Committee staff, the former NIMH technology transfer director 
acknowledged that this was an oversight.
        b. Plasma samples transferred without MTA.  According to 
records from Pfizer and others, NIMH shipped 388 plasma samples 
to Pfizer on August 19, 2002.   The Committee has no records of a 
material transfer agreement covering these plasma samples. The 
April 1998 MTA and the October 6, 2000, amendment to this 
MTA only covered coded clinical samples of spinal fluid and 
serum.  
        c. Questionable amendment to MTA.  The April 1998 MTA 
was executed using the Public Health Service Agreement MTA 
form and Dr. Sunderland was listed as the provider at his NIMH 
address.  The October 6, 2000, amendment to the April 1998 MTA 
was executed on Pfizer letterhead and listed Dr. Sunderland at his 
home address.  Committee staff asked NIH whether there were any 
amendments to the 1998 Pfizer MTA.  NIH told the Committee 
staff that the NIMH Technology Transfer Office did not have an 
amendment but then NIMH asked Dr. Sunderland if there had been 
any amendments.  At that point, Dr. Sunderland produced the 
October 2000 amendment.  In an interview with Committee staff, 
the NIMH Technology Transfer Director stated that this 
amendment "would have raised eyebrows."   Even though NIH 
told the Committee staff that Dr. Sunderland had the signatory 
authority to execute an MTA in 2000, because Dr. Sunderland had 
executed the MTA and had it co-signed by the NIH Scientific 
Director, the same process of authorization in effect in 1998 should 
have been used for the amendment in 2000.
 	d. NIMH policy on MTAs lacked basic controls of 
accountability.  According to an NIH e-mail to Committee staff, 
Dr. Sunderland had the authority to transfer the spinal fluid 
samples to Pfizer on his own without any approval or reporting, as 
long as Dr. Sunderland chose not to document the transfer without 
an MTA.  Because he chose to execute an MTA, however, he did 
not have authority on his own to provide the samples.  He needed 
clearance from the NIH Scientific Director.  In other words, NIMH 
policy at the time, as represented by NIH, gave scientists more 
authority to provide government property to non-government 
researchers without any paperwork than if the scientists chose to 
do the paperwork.   This kind of system raises the question 
whether such a
policy incentivized a lack of accountability. 
        Moreover, in 1999 the NIMH changed its written 
delegations of authority to permit Branch Chiefs, such as Dr. 
Sunderland, to have sign-off authority on MTAs.  The stated 
rationale was to ensure that branch chiefs were aware of what 
materials were coming and going from the labs under their 
supervision.  According to NIH in an e-mail to Committee staff,  
Dr. Sunderland had the authority after May 24, 1999 to approve his 
own transfers of material (including human tissue samples) outside 
NIH.  This NIMH policy, or perhaps policy interpretation, raises 
the question about the lack of essential checks and balances to 
protect against fraud and error because the Branch Chief could 
approve his own MTAs for samples from studies in which he was 
involved as the Principal Investigator.
 	e. Lack of clarity in NIMH policy on MTAs.  Committee 
staff found an information bulletin, "NIH Technology Transfer and 
You," posted on the NIMH Technology Transfer Office (TTO) 
web site.  The bulletin stated that that the NIMH version was 
revised on February 24, 2000. This bulletin stated in boldface type:

	Current NIH policy requires that MTAs be used whenever 
an NIH scientist sends out or receives materials, e.g., cDNAs, 
cell lines, antibodies, etc.  These agreements must be signed by 
authorized IC personnel. 

The NIMH TTO Director at that time told Committee staff in an 
interview that MTAs were required.  Other NIMH officials and 
NIH, however, disputed that the policy was so clear-cut.  Rather, 
scientists were encouraged to use MTAs but not required to do so.  
In other words, MTAs were discretionary.  NIMH officials 
interviewed by Committee staff also were not familiar with the 
TTO Bulletin.  This area raises a question about the adequacy and 
accuracy of internal communication at NIMH.  There is also a 
question about what was the actual policy.

        f.  The MTA was a questionable mechanism for the 
transfer.  Committee staff obtained records showing that Dr. 
Sunderland was the provider of spinal fluid samples in a 1989 
Cooperative Research and Development Agreement (CRADA) 
between NIMH and Abbott Laboratories.  Under this CRADA, Dr. 
Sunderland provided 115 samples of spinal fluid to Abbott.  NIH 
and NIMH officials could not distinguish between the Abbott 
transfer and the Pfizer transfer in terms of why a CRADA was 
used with the transfer to Abbott but not with the one to Pfizer in 
1998. Moreover, at a 1999 NIH Conference on Biomarkers, Dr. 
Sunderland stated: "In a large-scale collaboration between the 
NIMH, Pfizer, and OGS, we have embarked on a series of studies 
focused on one very important part of biomarker puzzle," and later 
stated that "cerebrospinal fluid markers are the focus of our 
collaborative efforts with Pfizer and OGS."  (Emphasis added). 
Given such characterizations of the activity with Pfizer and OGS 
as well as other information, these officials believe that Dr. 
Sunderland and Pfizer were in fact engaged in a collaboration in 
which a CRADA would have been the appropriate mechanism to 
use.
 	g.  Reference to third-party collaborator in MTA should 
have triggered more scrutiny.  Provision #2 in the April 1998 
MTA stated that: "The Research Material will only be used for 
research purposes by Recipient and Recipient's collaborator in the 
UK, for the research projects described below, under suitable 
containment conditions."  The mention of the Recipient's 
collaborator in the UK was a reference to Oxford Glycosciences, 
Ltd., (OGS), as part of the collaboration with Pfizer.  OGS was 
part of the three-way collaboration with Pfizer and NIMH.  OGS 
used 2D gel electrophoresis techniques to detect proteins in spinal 
fluid.  OGS was not, however, specifically identified in the MTA. 
The involvement of a third-party collaborator raises a question of 
whether this was a modification of a routine material transfer and 
should have triggered further scrutiny from the Technology 
Transfer Office.  The question is raised about whether uses and 
recipients of samples are adequately reported in the MTA and 
whether NIMH should have been made more aware of OGS and 
the use of the samples.  Moreover, the MTA authorized the transfer 
of spinal fluid samples for the narrow purpose of the collaboration, 
which Pfizer refers to as the "unknown biomarker" projects.  
Records, however, produced to the Committee show that Dr. 
Sunderland provided over 2,100 samples to Pfizer for the "known 
biomarker" project.  OGS, however, was not involved in this 
collaboration and it was actually a separate biomarker research 
project.  A question is further raised whether the 2100 samples sent 
to Pfizer for this project were entirely unauthorized.  
        h.  Most of the samples transferred to Pfizer may not have 
been covered by the MTA and the MTA amendment.  As 
mentioned before, the terms of the MTA related to transfers for the 
research purpose of the three-way collaboration of NIMH, Pfizer, 
and OGS.  Pfizer calls this collaboration the "unknown 
biomarkers" project.  The second project between Dr. Sunderland 
and Pfizer, did not involve OGS and Pfizer calls this "the known 
biomarker project."  The NIH documents produced to the 
committee relating to the Pfizer collaboration state that the total 
number of samples sent to Pfizer equals 2132 vials for beta-
amyloid 1-42, beta-amyloid 1-40, and tau. These are known 
biomarkers and relate to the "known biomarker" project.  One of 
the NIH documents asserts that the samples sent to Pfizer were 
"through the NIH-approved MTA."  The Committee, however, has 
not received any records of any MTA covering the known 
biomarker project.  It is highly questionable whether NIH 
technology transfer and legal officials would find that the April 
1998 MTA for the unknown biomarker project could be used to 
authorize transfer for the known biomarker project, even though it 
involved the same company and the same area of research, because 
the samples were used for a different research purpose.

Science management concerns  
        Three important concerns were raised:  lack of retention of 
clinical research data, conflict of interest in committing NIH 
scientific resources, and NIH oversight of unpublished research.
 	a. Lack of retention of clinical research data.  When Dr. 
Molchan inquired about getting the leftover spinal fluid samples, 
she also asked about getting the data from her uncompleted lithium 
study.  Dr. Sunderland informed Dr. Molchan that this data was no 
longer available:  

            "Dear Sue, 
            Over the last few days, we have been searching electronic 
files and paper files to see what we could find.  Unfortunately, the 
data is no longer available.  Just so you know, we had to go 
through several purges over the last few years when we moved 
offices, and anything over 5-7 years old was subject to purging.  
Since these studies and the resultant publications go back over 15 
years in some cases, they were not carried forward to our limited 
space. . . . " (Trey Sunderland e-mail , March 14, 2005 to Susan 
Molchan).
         Dr. Molchan raised the issue of data retention in an e-mail 
to Committee staff: "Does NIH have a policy on what happens to 
data like this when scientists leave the NIH?  It seems wasteful to 
repeat the same studies without having earlier results."

        Two senior NIH officials provided somewhat conflicting 
information.  One official confirmed the policy of purging clinical 
data after seven years.  Another official, however, had never heard 
of such a policy.  The Subcommittee may wish to raise this 
question with NIH about what the policy is, and what the policy 
should be, on retention of clinical research, particularly in cases 
where the researcher has left NIH.
        b. Commitment of resources.  Dr. Sunderland's 
collaborations with Pfizer resulted in the shipment of over 3,000 
spinal fluid and plasma samples.  These samples were 
extraordinarily valuable, both scientifically and commercially, 
because they contained useful information, they were linked to 
well-characterized clinical data (lots of medical details about the 
subjects), and the samples were taken from these same subjects 
over different points in time over several years.  The Committee 
staff could find no evidence that showed in 1998 any NIMH 
official besides Dr. Sunderland who was even aware, much less 
supportive, of the merits of the Pfizer collaboration.   Thus, Dr. 
Sunderland, while having concurrent financial interests with 
Pfizer, made the decision to commit 3,000 non-renewable 
taxpayer-supported human research samples.
        Techniques employed in proteomic analysis are new and 
evolving.  Even if Dr. Sunderland may have been the scientist in 
the best position to evaluate whether the OGS technology was 
promising enough to consume these valuable human tissue 
samples, the intramural research program at NIMH or NIH may 
have had more than one expert in proteomics to assist in such a 
decision.  Could Dr. Sunderland's scientific judgment have been 
better informed by consultations with other proteomic experts at 
NIH?  The Pfizer projects may have been the most promising 
collaboration available in the search for biomarkers of Alzheimer's 
disease.  Could an exploration of other private sector or academic 
partners produced a more promising result?  Most importantly 
should a single scientist be the sole decisionmaker about the best 
use of these unique human tissue samples, especially with direct 
financial interests involved?
        c.  NIH oversight of unpublished research.  In the year 2000, 
Dr. Sunderland prepared a document  called  "Overview - GPB," 
in preparation for a review by the NIMH Board of Scientific 
Counselors.  On page 3 of this document, the discussion about the 
Pfizer/OGS collaboration is as follows: 

"Perhaps the most interesting interaction is the three-way 
collaboration between the NIMH, Pfizer, Inc., and Oxford 
Glycosciences in England.  This cooperative approach was first 
established in 1998 to investigate protein spots in the CSF of AD 
subjects and 'at risk' controls at baseline and over time.  While this 
convergence of government investigators, the pharmaceutical 
industry, and a biotechnology firm has been highlighted  by the 
NIH Director at a recent national biomarkers meeting as a way to 
leverage resources and scientific interest in the future, the proof of 
its power must come from the data, especially over time.  Using 
high-throughput, exquisitely sensitive 2D gel electrophoresis 
techniques which provide quantitative data reflecting the up- and 
down-regulation of proteins in human CSF, we are generating 
cross-sectional data on over 1200 proteins in groups of AD and 'at 
risk' subjects. Perhaps most importantly, we will have longitudinal 
data in both these groups through repeat CSF collections that will 
allow us to track protein changes through the evolution of this 
illness."  

        Under normal circumstances, the BSC would have been 
scheduled for another review of Dr. Sunderland's work in 2005.  
However, because in late 2004, NIMH officials believed that Dr. 
Sunderland was going to be leaving the NIH the BSC review was 
cancelled.  The Committee staff has not found any publications 
related to the Pfizer/OGS collaboration.  When asked by 
Committee staff to retrieve data or some kind of workproduct that 
resulted from this collaboration, NIH was unable to do so.  In an 
interview with Committee staff, Karen Putnam indicated that all 
data related to the unknown biomarker project was maintained on-
site at Pfizer.  As Ms. Putnam noted in her December 7, 2004, 
letter to NIH: 

"Pfizer asked me to consult in the fields of statistics and data 
management.  I was involved in specific projects exploring 
proteomics and statistical methodology.  The Pfizer activities 
centered around discovery research, where the results were used to 
generate future hypotheses and directions of research.  The results 
generated from my Pfizer outside activities were not part of the 
data involved in my current government job.  All proteomics data 
were confidential and kept at the Pfizer site.  The computer 
software and hardware used in exploring proteomics data was 
located at the Pfizer site." 

Outside counsel to Pfizer confirmed to Committee staff that this 
was essentially correct.
Thus, the available evidence is that the unknown biomarkers 
project (or "discovery research" per Ms. Putnam) did not generate 
data that came into possession of the NIH.  Under these particular 
circumstances, NIH was unable to report to the Committee what 
this collaboration had produced for NIH's scientific research 
program.

Conclusion
	In sum, the records and interviews conducted in this 
investigation raise serious questions of misconduct in connection 
with, and inadequate oversight and control over, human tissue 
samples in NIH intramural programs. It should be noted that the 
Committee staff found no evidence that Pfizer had any knowledge 
relating to the questionable conduct of Dr. Sunderland in 
connection with the April 1998 MTA and the subsequent 
shipments of samples.   Members of the Subcommittee may wish 
to pursue these questions at the hearing with witnesses and/or other 
appropriate action. 



	MR. WHITFIELD.  At this time, we have about 4 minutes left to 
cast two votes on the House floor, so Dr. Molchan, I will apologize 
to you, but we are going to take a recess here, go vote, and then we 
will be right back.  We look forward to your testimony as soon as 
we return.
	So thank you.  We will get your opening statement when we 
get back.
	[Recess]
	MR. WHITFIELD.  I would like to reconvene this hearing, and 
we had indicated that we would have an opening statement from 
Ms. Baldwin when we resumed and she is not here, so at this time I 
would like to recognize Mr. Stearns of Florida for his opening 
statement.
	MR. STEARNS.  Thank you, Mr. Chairman.  I certainly want to 
thank you for holding this hearing and your leadership here in 
prodding everyone to do this, today and tomorrow, surrounding the 
NIH policies on tissue samples.  I also want to thank Dr. Molchan 
for testifying today and for the courage for coming to the 
subcommittee when you were troubled about this concern.
	This hearing will ask if NIH has adequate policies in place to 
prevent diversion of human tissue samples for unauthorized 
purposes, and what is NIH policy on a chain of custody 
documenting human tissue samples from subject to each researcher 
that touches these samples, inside and out of NIH.  Are we tracking 
the inventory or just willy-nilly sticking values on donations 
because this is what they are, a patient's literal blood, sweat, and 
tears, in the freezer with no tracking, no checks, and no balances.  
In other words, where is the oversight, where is the accountability 
here?
	This hearing raises the question about conflicts of interest at 
NIH, researchers involved in outside research assignments in 
industry.  At the hearing in the summer of 2004, I was one who 
questioned Dr. Sunderland about a lucrative outside financial 
contract he had with Pfizer, and that now has surfaced again in this 
hearing.  The extramural research that NIH funds and is supposed 
to oversee so carefully sends positive rippling effects across 
organizations, academia, and facilities across the United States.  
For example, Alzheimer's disease, neuro-imaging initiative, 
ADNI, for which the doctor as the program director relies on 
software-supported imaging equipment developed and 
manufactured by Siemens, Phillips, and General Electric.  The 
three primary companies that develop and manufacture imaging 
are providing for the imaging aspects of the project, while the 
company that manufactures magnetic resonant imaging, the MRI 
coils that these giants of diagnostic imaging use, make them in 
Gainesville, Florida, in my congressional district.  So many 
different people depend on the integrity of NIH human tissue 
policies, from patients hoping and praying for a cure for their 
disease to biotech companies to small engineering firms.  
	Lastly, another question they have about this hearing is when 
the research subjects submitted a specimen CFS, did they consent 
to just a single study or did some at the NIH think it was a blanket 
consent for multiple uses and/or free reign over their spinal fluids 
for various research studies?  In answer to that, I am troubled that 
it seems some at NIH did, in fact, handle these CFS specimens 
carelessly, sending them unauthorized to Pfizer without de-
identifying them.
	Again, this committee has passed my data bill, H.R. 4127, 
which applies only to industry, but it sounds like we need to 
consider Federal agencies handling of Social Security and other 
sensitive personal data as well.
	Mr. Chairman, I thank you for exploring these issues and I 
yield back.
	[The prepared statement of Hon. Cliff Stearns follows:]

PREPARED STATEMENT OF THE HON. CLIFF STEARNS, A 
REPRESENTATIVE IN CONGRESS FROM THE STATE OF FLORIDA

        I want to thank Chairman Whitfield for holding this hearing 
today and tomorrow surrounding NIH policies on tissue samples.  
And Dr. Molchan, thank you for testifying today, and for your 
courage in coming to this Subcommittee when you were troubled.
	This hearing will ask if NIH has adequate policies in place to 
prevent diversion of human tissue samples for unauthorized 
purposes?  And, what is NIH's policy on a chain of custody, 
documenting human tissue samples from subject to each researcher 
that touches it, inside and outside of the NIH?  Are we tracking the 
inventory, or just willy-nilly, sticking valued donations, because 
that is what they are, of patient's literal blood, sweat and tears, in 
the freezer with no tracking, no checks and balances?  Where is the 
oversight, the accountability? 
	Also, this hearing raises questions about conflicts of interest of 
NIH researchers involved in outside research assignments in 
industry.  At the hearing in the summer of 2004, I was one who 
questioned Dr. Sunderland about a lucrative outside financial 
contract he had with Pfizer, that now surfaces again in this hearing. 
	The extramural research that NIH funds, and is supposed to 
oversee so carefully, sends positive rippling effects across 
organizations, academia, and facilities across the nation.  For 
example, the Alzheimer's Disease Neuroimaging Initiative 
(ADNI), for which Dr. Molchan is the program director, relies on 
software support and imaging equipment developed and 
manufactured by Siemens, Philips, and General Electric, the three 
primary companies that develop and manufacture imaging 
equipment.  Well, the company that manufactures the magnetic 
resonance imaging (MRI) coils that these giants of diagnostic 
imaging use makes them in Gainesville, Florida:  INVIVO 
Corporation. So, many different people depend upon the integrity 
of NIH's human tissue policies, from patients hoping, praying for a 
cure for their disease, to biotech companies, to small engineering 
firms.
	Another question I have about this hearing is when the research 
subjects submitted a specimen of cerebrospinal fluid (CSF), did 
they consent to just a single study, Dr. Mochan's? Or did some at 
the NIH think that it was a blanket consent for multiple uses and/or 
free reign over their spinal fluid for various research studies?  
	And, advancing from that, I am troubled that it seems some at 
the NIH did in fact handle these CSF specimens carelessly, 
sending them, unauthorized, to Pfizer without de-identifying them!  
Again, this committee has passed my DATA bill, HR 4127, which 
applies only to industry, but it sounds like we need to consider 
federal agencies handling of Social Security numbers and other 
sensitive, personal data as well.
Thank you for exploring these issues.  

	MR. WHITFIELD.  Thank you, Mr. Stearns.  
	At this time I recognize Ms. Baldwin from Wisconsin.
	MS. BALDWIN.  Thank you, Mr. Chairman.
	The NIH is one of our national treasures.  The intramural 
research done at NIH and the extramural research done in 
cooperation with outside partners is truly amazing and sometimes 
awe-inspiring.  So much of today's most promising research 
involves human tissues.  In order to translate biomedical 
discoveries into real improvements for people's medical care, we 
must first use human tissues to test a treatment or develop a new 
theory about how a disease develops.  The work that is done with 
these human tissues holds the potential to do so much to advance 
human health.
	I am distressed to hear about apparent lapses in accountability 
with regard to human tissue samples collected at the NIH.  Why 
doesn't the NIH have a centralized system for tracking its tissue 
samples?  Why is there no institute-wide inventory or accounting 
of what happens to these samples when a study ends?  As our full 
committee and the Subcommittee on Health engage in discussions 
about health information technology, it seems like NIH could be a 
leader in this regard but at least in this arena, it certainly is not.
	I think that what is most shocking to me is the carelessness and 
the way in which some at NIH appear to be treating such a 
precious commodity.  While it is true that the samples are in 
freezers across the NIH and they might be vials of fluid or dishes 
of cells, it is important for us to remember that each of these 
samples originated in a person, and that person chose to share, 
chose to make a gift so that research could advance.  At the very 
least, we must have practices in place that guarantee donor privacy 
and we need to ensure that donors are giving informed consent 
about how their donation will be used.  
	Lastly, a lot of these human tissues are non-renewable, and as I 
said earlier, they are a precious resource.  We need to make sure 
that they are being used in the most appropriate and ethical way, 
not simply handed off to private companies.
	Again, I am really shocked that some at the NIH would treat 
human tissues so carelessly, and that individual researchers would 
be given almost complete control over tissue samples without 
having to report to an impartial IRB, Institutional Review Board, 
like researchers at every academic research institution have to do.
	I look forward to today's discussion, and I hope this hearing 
will lead us towards some answers.  I want to extend a special 
thank you to today's witness, Dr. Molchan.  I commend you for 
bringing information forward to this committee's attention.
	Thank you, Mr. Chairman.  I yield back.
	MR. WHITFIELD.  Thank you.  At this time, I will recognize the 
full committee Chairman, Mr. Barton of Texas.
	CHAIRMAN BARTON.  Thank you, Mr. Chairman, for holding 
this hearing.  As I said at the last set of oversight hearings on NIH, 
the hallmark of this committee has always been its oversight 
responsibility and its willingness and ability to hold agencies 
responsible under its jurisdiction that produces results and better 
government and better services for the American people.
	When we held oversight hearings about the NIH ethics system 
several years ago, we found that there were weaknesses in the 
system at that time, and that those weaknesses were more severe 
than we had previously recognized.  To his credit, Dr. Zerhouni, 
who had a ringside seat at those hearings, took the facts of the 
hearing seriously and changed and reformed the NIH ethics 
system.
	Today, we are going to take a look at how the NIH protects its 
most precious assets, that is, the material that is at the core of NIH 
research mission, human tissue samples.  Once again, after 
extensive investigation, on a bipartisan basis, I might add, we have 
found deeper concerns regarding human tissue samples at NIH 
than we first believed.  We have found a lack of a centralized 
database, lack of oversight.  This lack of a centralized database and 
lack of oversight could, and probably does, leave NIH laboratories 
vulnerable to the risks of theft and abuse.  We know from previous 
investigations that the NIH has an inventory system, but NIH tells 
us that it has no centralized inventory system that could tell the 
NIH director how many vials of tissues are in freezers at a 
particular institute.  It would really be a shame if we find out that 
the National Institutes of Health has more control over its 
paperclips and trashcans than it has over its human tissue samples.
	The committee has investigated a case and found evidence of a 
serious breach of trust.  This case is focused on Dr. Trey 
Sunderland, who is supposed to be a witness later today in these 
hearings.  He is a very noted, and I might add, respected researcher 
in the field of Alzheimer's disease.  I wish we were holding a 
hearing to congratulate him on some great discovery that he has 
made to cure or at least alleviate the hazards of Alzheimer's.  
Instead, we are going to have to discuss a way of how he used his 
position to use NIH spinal fluid samples to further his own 
undisclosed personal consulting.  The information provided so far 
to the committee shows that a private corporation, Pfizer 
Corporation, paid Dr. Sunderland $285,000 during the 1998-2003 
time period to consult on two projects involving spinal fluid 
samples that Dr. Sunderland had sent to Pfizer.  During the same 
time period, Pfizer also paid Dr. Sunderland approximately 
$300,000 for lectures.  These figures don't count an additional 
$200,000 for undisclosed activities with other companies.  There is 
evidence that he advised his subordinate to conceal these 
consulting activities involving the samples.  This is from an 
official who chaired for 10 years the committee that reviews the 
ethics of conducting mental health research on human beings.  This 
certainly appears to be a betrayal of the public trust that NIH so 
much stands for.
	These hearings underscore the need to enact NIH 
reauthorization and reform legislation.  The NIH director must 
have some baseline of information about NIH assets if we are 
going to gain new efficiencies and hopefully more effective ways 
to translate research into better healthcare.  NIH reauthorization 
legislation is of the highest importance.  Out of this investigation, 
deserving questions and concerns, we can use these hearings to 
make NIH stronger and better.  
	The National Institutes of Health is, indeed, a national treasure.  
It must be cherished, protected, nourished, and allowed to flourish.  
Today's hearing is a first step towards strengthening the public 
trust in NIH and preserving confidence in its integrity.  I want to 
thank you, Mr. Chairman, and also the subcommittee Ranking 
Member, Mr. Stupak, for the bipartisanship nature of this 
investigation.  I would also like to thank the Ranking Member of 
the full committee, Mr. Dingell of Michigan, for his support.  
	Finally, I want to say that I look forward to working with Dr. 
Zerhouni and others to improve in this area and to help NIH 
become better managed, and thus be able to deliver the results for 
the health of America that we so depend on NIH to do.
	With that, Mr. Chairman, I yield back.
	[The prepared statement of Hon. Joe Barton follows:]

PREPARED STATEMENT OF THE HON. JOE BARTON, CHAIRMAN, 
COMMITTEE ON ENERGY AND COMMERCE

        Mr. Chairman, I am glad you are holding these hearings.
	As I said at the last set of NIH oversight hearings, I hope one 
of the hallmarks of my chairmanship of the Energy and Commerce 
Committee will be holding agencies responsible and produce better 
government and better services and policies for the American 
people.
	Two years ago, when we held oversight hearings about the 
NIH ethics concerns, we discovered that the weaknesses in the 
NIH system were severe.  Dr. Zerhouni, the Director of NIH, had a 
ringside seat and realized that NIH's reputation was on the line.  In 
light of our hearings, the NIH ethics system has been overhauled 
and reformed.

	Today we look at how NIH protects precious assets, the human 
tissue samples that are at the core of the agency's research mission.   
Once again, after extensive investigation, we have found deeper 
concerns regarding human tissue samples at NIH than first 
believed.  Incredibly, we have found a lack of a centralized 
database and oversight at NIH that leaves NIH labs vulnerable to 
theft and abuse.  We know from previous investigations that NIH 
has an inventory system for its property, but NIH tells us it has no 
centralized inventory system that could tell the NIH Director how 
many vials of tissue are in freezers at a particular institute.  It 
appears that the agency can account for its paper clips better than 
its invaluable research material.
	The Committee's investigation has focused on one particularly 
brazen breach of trust.  Dr. Trey Sunderland, a noted and respected 
researcher in the field of Alzheimer's disease, has discovered 
something that may have been even more important to him.  He 
has discovered how to make money by using NIH's collection of 
spinal fluid samples in an undisclosed, personal consulting 
arrangement with a drug company.   The information provided to 
the Committee is that Pfizer paid Dr. Sunderland $285,000 during 
the 1998-2003 time period to consult on two projects involving 
spinal fluid samples Dr. Sunderland sent to Pfizer.   During this 
same time period, Pfizer also paid Dr. Sunderland around $300,000 
for lectures.  He also earned almost $200,000 more for undisclosed 
activities with other companies.  
        Dr. Sunderland might have been proud of his work, but he 
wasn't.  There is evidence that he advised his subordinate to 
conceal consulting activities involving the samples.  All this from 
an official who for 10 years chaired a committee that reviews the 
ethics of conducting mental health research on human beings.   Mr. 
Chairman, this amounts to a breathtaking betrayal of the public 
trust and of NIH values.
	These hearings underscore the need to enact NIH 
reauthorization legislation.  The NIH Director must have some 
baseline of information about NIH assets.  If we are going to gain 
new efficiencies and hopefully more effective ways to translate 
research into better healthcare, enacting NIH reauthorization 
legislation is of great importance.
	Out of this investigation of disturbing questions and concerns, 
we can use these hearings to make NIH stronger.  NIH is indeed a 
national treasure.  It must be cherished.  Today's hearings are a 
first step toward strengthening public trust in NIH research and 
preserving confidence in NIH's integrity.
	I thank you and Mr. Stupak for the bipartisan investigation.  I 
also thank Mr. Dingell for his support of this investigation.  
Finally, I look forward to working with Dr. Zerhouni and the 
leadership of NIH on this matter and helping NIH become better 
managed and better able to improve the health of the American 
people.

	MR. WHITFIELD.  Thank you, Chairman Barton.
	At this time I recognize Mr. Walden of Oregon for his opening 
statement.
	MR. WALDEN.  Mr. Chairman, I am going to waive an opening 
statement this afternoon.  Thank you.
	MR. WHITFIELD.  Thank you.
	Mrs. Blackburn of Tennessee.
	MRS. BLACKBURN.  Mr. Chairman, I will waive and reserve my 
time for questions.
	[Additional statement submitted for the record follows:]

PREPARED STATEMENT OF THE HON. DIANA DEGETTE, A 
REPRESENTATIVE IN CONGRESS FROM THE STATE OF COLORADO	

        Mr. Chairman, thank you for holding this important hearing.  
The issue is not just about the alleged wrongdoing of one research 
scientist at the National Institutes of Health (NIH).  The larger 
issue we face is the systemic breakdown in how we protect patients 
who courageously agree to participate in clinical research.  The 
NIH is the premiere biomedical research entity in the world.  As a 
result, it is imperative that the research protocols used by the NIH 
be of the highest integrity.  Clearly, that is currently not the case.
        Let me first recognize our witness today, Dr. Susan Molchan, 
who brought this issue to the attention of the subcommittee.  I 
believe we all owe you a debt of gratitude for coming forward.  
        Tomorrow we will hear from a number of witnesses from the 
NIH.  The subcommittee's staff report raises many issues that our 
NIH witnesses must answer and I look forward to questioning the 
agency tomorrow about a number of my concerns.
        Specifically, I am concerned that it appears as though the NIH 
cannot account properly for human tissue samples in its possession 
or for the data generated by the use of those samples in biomedical 
studies.  
        I would posit that the oversight function at NIH is in need of 
serious repair.  Its investigatory ability is clearly inadequate when 
this Subcommittee has to uncover what the NIH cannot, even when 
it is trying.  I sincerely hope that these hearings will assist the 
agency in straightening up the mess caused by its administrative 
shortcomings, just as our last hearings helped the NIH shore up its 
ethical standards.
        When he was shown the extent of the ethical loopholes at his 
agency, NIH Director Dr. Zerhouni was very responsive.  I have no 
doubt that he will be equally responsive in addressing the travesty 
created by the lack of accountability that this inquiry has 
uncovered.  
        All that said, what is most worrisome to me is the abuse of 
patients' trust.  These people, victims of Alzheimer's Disease or 
their relatives, as well as some courageous individuals who have 
participated in the control groups, have submitted periodically for a 
decade or more to time consuming and painful spinal taps.  They 
believed that the decisions regarding the use of these samples were 
made by the best scientific judgment in the country.  
        It is possible that only such an esteemed institution as the NIH 
could have enlisted these volunteers and convinced them to return 
again and again to give spinal fluid.  Yet, we now know that some 
of these committed patients were never told that the experiments 
that used their samples had been aborted. Others were never given 
the results of completed efforts.  Nobody was informed that 
samples left over from certain experiments were shipped from the 
NIH to private drug companies.  Patients were not informed that 
there was a chance that their names, names that were supposed to 
be divorced from the samples in the event of them being used for 
research, could be inadvertently revealed.  This did in fact occur 
when one of the Sunderland shipments to Pfizer revealed patient 
names to company researchers.
        Mr. Chairman, these practices are unacceptable.  Human 
subjects and their donated tissues simply must be protected as a 
first order of business by government researchers.  The officials at 
NIH must be able to give ironclad assurances to these volunteers.  
To solicit cooperation and to take human tissue without proper 
protections in place is simply wrong, whether it is at the NIH or 
anywhere else.
        Last week, I introduced H.R. 5578, the "Protection for 
Participants in Research Act of 2006" to provide clear and 
consistent protections for human subjects who take part in clinical 
trials, as well as providing clear guidelines to those conducting 
medical research.  Specifically, this measure strengthens patients' 
rights to informed consent before subjecting to human subjects 
research.  Perhaps this bill, given what we hear today and 
tomorrow from our panelists, could be used as a basis for further 
protecting human subjects, whether it is at the NIH, in universities, 
or at private companies.
        I yield back the balance of my time.

	MR. WHITFIELD.  Thank you.  That concludes our opening 
statements, and at this time, Dr. Molchan, we will call you as our 
first and only witness of the day.
	Dr. Susan Molchan is the Program Director of the AD 
NeuroImaging Initiative, Neuroscience and Neuropsychology of 
the Aging program at the National Institute on Aging.  Dr. 
Molchan, as you may or may not know, in the Oversight and 
Investigations Subcommittee, we do have, as a matter of policy, to 
take testimony under oath.  I would ask you, do you have any 
objection to testifying under oath today?
	DR. MOLCHAN.  No, I don't.  That is fine.
	MR. WHITFIELD.  Okay.  Under the rules of the House and also 
the rules of the committee, you are entitled to be advised by legal 
counsel.  Do you have legal counsel with you today?
	DR. MOLCHAN.  No, I don't.
	MR. WHITFIELD.  You are on your own?
	DR. MOLCHAN.  Yeah.
	MR. WHITFIELD.  If you would stand, I would like to swear you 
in.
	[Witness sworn]
	MR. WHITFIELD.  Thank you.  You are now under oath, Dr. 
Molchan, and at this time I recognize you for 5 minutes for your 
opening statement.

STATEMENT OF SUSAN MOLCHAN, M.D., PROGRAM DIRECTOR, AD NEUROIMAGING 
INITIATIVE, NEUROSCIENCE AND NEUROPSYCHOLOGY OF AGING PROGRAM, NATIONAL 
INSTITUTE ON AGING, NATIONAL INSTITUES OF HEALTH, U.S. DEPARTMENT OF HEALTH 
AND HUMAN SERVICES

	DR. MOLCHAN.  Thank you, Mr. Chairman.  Mr. Chairman and 
members of the committee, my name is Dr. Susan Molchan from 
the National Institute on Aging at the NIH where I have worked 
since 2001 as the Program Director for clinical studies and 
Alzheimer's disease.  I serve as a medical officer in the 
Commissioned Corps of the United States Public Health Service.  
Thank you for this opportunity to participate today.  I have been 
asked to address my experience with human tissue samples at the 
National Institute of Mental Health where I worked for 9 years.  I 
will address my experience specifically with one type of especially 
precious sample, spinal fluid, that I collected from a number of 
patients with Alzheimer's disease and volunteers in the early '90s.
	As a young scientist at the NIMH, National Institute of Mental 
Health, I conceived and conducted a study that now has 
implications for Alzheimer's research.  In the process of my 
research, I obtained a very valuable material, spinal fluid.  These 
samples can be obtained only with the consent and understanding 
of each and every patient.  As a doctor, my first obligation is to 
advocate for patients who put their trust in me.  Some of these 
patients had contributed their time and bodies to a number of my 
research studies and others at the NIMH.  These good people are 
always ready to help and work on Alzheimer's in any way my 
colleagues and I asked. 
	While at NIMH, a redirection of the program occurred.  New 
goals made it impossible for me to continue my work.  Lack of 
support was intense and I was not encouraged to stay, so I went to 
work at the FDA for a few years until 2001, when I was recruited 
to my current position as a program officer at the National Institute 
on Aging where I work with Alzheimer's scientists throughout the 
country. 
	In 2004, some of these scientists, university scientists who are 
leaders of the National Institute of Aging's clinical trials 
consortium where I work now, which serves as the primary 
mechanism through which NIH funds studies on the treatment of 
Alzheimer's disease, proposed a study very similar to the one I had 
done while at the National Institute of Mental Health.  Several of 
my very esteemed colleagues pressed me to obtain the samples I 
had collected.  Such samples can be stored in freezers for years, 
and my colleagues and I had every reason to believe that they 
would still be available.
	The head of the branch where I worked at NIMH located and 
sent a small subset of the spinal fluid samples to a university 
colleague for analysis.  Twenty-five people had participated in the 
study, although I couldn't recall on how many I had collected 
spinal fluid for sure.  Some got one spinal tap, others had gotten 
two.  I did know I had collected it on more than the eight 
Alzheimer's patients and two volunteers on whose fluid was 
located.  The individual responsible for the samples at the NIMH, 
Dr. Sunderland, e-mailed me that some of the samples had been 
lost in freezer thaw problems.  A request to inspect the freezers to 
hopefully help find some samples was denied.
	By the end of January 2005, intriguing data resulted from 
analyses of the spinal fluid samples that we were able to recover.  
Incomplete as it was, it contributed to the success of a grant 
proposal that shows promise in advancing knowledge on the 
mechanisms and treatment of Alzheimer's disease.  Several 
colleagues agreed that the data from these samples were worth 
publishing in a scientific journal.  These senior Alzheimer's 
researchers again pressed me for an answer as to why only a small 
amount of fluid was available, and only on a subset of the 
participants.  This would need to be explained in any scientific 
submission of the data.
	Since Congress had shown an interest in this matter, some 
progress has been made.  I thank you for your interest in human 
tissue specimens that are so important to public health research.
	Thank you.
	[The prepared statement of Susan Molchan follows:]

PREPARED STATEMENT OF SUSAN MOLCHAN, M.D., PROGRAM 
DIRECTOR, AD NEUROIMAGING INITIATIVE, NEUROSCIENCE AND 
NEUROPSYCHOLOGY OF AGING PROGRAM, NATIONAL INSTITUTE ON 
AGING, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF 
HEALTH AND HUMAN SERVICES

        Mr. Chairman and Members of the Committee:
        My name is Dr. Susan Molchan, from the National Institute on 
Aging (NIA) at the National Institutes of Health (NIH), where I 
have worked since 2001 as a program director for clinical studies 
on Alzheimer's disease. I serve as a medical officer in the U.S. 
Public Health Service. Thank you for this opportunity to 
participate today.
 	I have been asked to address my experience with human tissue 
samples at the National Institute of Mental Health (NIMH), where 
I worked for nine years. I will address my experience specifically 
with one type of especially precious sample-spinal fluid- that I 
collected from a number of patients with Alzheimer's disease (AD) 
and volunteers in the early 1990s.
 	As a young scientist at NIMH, I conceived and conducted a 
study that now has implications for AD research. In the process of 
my research, I obtained very valuable material-spinal fluid. These 
human samples can be obtained only with the consent and 
understanding of each and every patient. Those who participate in 
our research trust that their fluid specimens will be handled 
carefully. As scientists, we carefully document and store this 
material. 
        As a doctor, my very first obligation is to advocate for the 
well-being and intentions of the patients who put their trust in me. 
Some of these patients had contributed their time and bodies to a 
number of my research studies and others at the NIMH. These 
good people were always ready to help in work on AD in any way 
my colleagues and I asked.
        While at NIMH, a redirection of the program occurred and the 
new goals made it impossible for me to continue my work. Lack of 
support was intense for this project and I was not encouraged to 
stay. I went to work at the FDA for a few years, until 2001, when I 
was recruited to my current position as a program officer at NIA, 
where I work with AD scientists throughout the country. 
        In 2004, the university scientists who are the leaders of the 
NIA's clinical trials consortium, which serves as the primary 
mechanism through which NIH funds studies on the treatment of 
AD, proposed a study very similar to the one I had done at the 
NIMH. Several of my esteemed colleagues pressed me to obtain 
the samples I had collected. Such samples can be stored in freezers 
for years, and my colleagues and I had every reason to believe that 
they would still be available. 
        As research on AD has progressed, the need for spinal fluid 
samples has increased, as they may shed light on treatment options 
for this increasingly prevalent and devastating disease. All 
available scientific resources are needed to fight AD. 
        The head of the branch where I had worked at NIMH located 
and sent a small sub-set (one cc per individual participant of the 
approximately 50 cc that I'd collected from each) of the spinal 
fluid samples to a university colleague for analyses (tests that were 
covered on the consent form under which study participants 
allowed me to collect their samples).
        Twenty-five people had participated in the study as 
documented on a Continuing Review memo to the NIMH IRB, 
dated July 1, 1993. Although I hadn't collected spinal fluid on all 
of them, I had collected it on more than the 8 AD patients and two 
volunteers on whom fluid was located. The individual responsible 
for the samples at the NIMH emailed me that some of the samples 
had been lost in "freezer thaw problems." A request to inspect the 
freezers to hopefully find some samples was denied. 
        By the end of January, 2005 intriguing data resulted from 
analyses of the spinal fluid samples that we were able to recover. 
Incomplete as it was, it contributed to the success of a grant 
proposal that shows promise in advancing knowledge on the 
mechanisms and treatment of AD.
        Several colleagues agreed the data from these samples were 
worth publishing in a scientific journal. These senior AD 
researchers pressed me for an answer as to why only a small 
amount of fluid was available, and on only a subset of the 
participants. This would need to be explained in any scientific 
submission of the data.
 	Since Congress has shown an interest in this matter, some 
progress has been made. I thank you for your interest in human 
tissue specimens that are so important to public health research.

	MR. WHITFIELD.  Dr. Molchan, thank you very much for 
cooperating with the committee and your willingness to come and 
testify.  
	How long were you actually at the National Institute of Mental 
Health?
	DR. MOLCHAN.  I worked at the National Institute of Mental 
Health for 9 years, from 1987 to 1996.
	MR. WHITFIELD.  Eighty-seven to '96, and was Dr. Sunderland 
there during that entire period?
	DR. MOLCHAN.  Yes, he was always my supervisor, yes.
	MR. WHITFIELD.  Okay, before I get to the lithium study, just to 
clarify here, when we talk about human tissue, and when we look 
at the specific testing that you were involved in, we are talking 
about spinal fluid?
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  But when we talk about human tissue in 
general, we are talking about things like subcellular DNA, we are 
talking about tissues like skin.
	DR. MOLCHAN.  Anything that comes from body parts.  Blood 
is a tissue, for example, spinal fluid is a tissue, as are the more 
solid--
	MR. WHITFIELD.  Okay.
	DR. MOLCHAN.  --components like skin.
	MR. WHITFIELD.  And fetal tissue, all of those things?
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  Okay.  Now, the lithium study that you were 
involved in, were you responsible for obtaining the spinal fluid for 
that study?
	DR. MOLCHAN.  I was responsible for obtaining most of the 
samples.  The study was initiated by me and if it was going to get 
done, I was the one who had to do it.  So I obtained most of the 
samples, though when I had to be somewhere else colleagues 
would step in and do so.
	MR. WHITFIELD.  And you said that the samples came from 
some Alzheimer's patients, as well as two patients who had no 
medical problems?
	DR. MOLCHAN.  The subset of the samples that were located 
last year, right.  There were several Alzheimer's patients, eight 
Alzheimer's patients and two of the normal volunteers that had 
done the study.
	MR. WHITFIELD.  So when you are dealing with an Alzheimer's 
patient, how do you obtain their consent for a spinal tap?
	DR. MOLCHAN.  We did have procedures, clear procedures in 
place for that and they would co-sign, have a spouse or someone 
else responsible co-sign and understand.
	MR. WHITFIELD.  And what was the total volume of spinal 
fluid that you were able to collect?
	DR. MOLCHAN.  Generally we collected approximately 25 cc's 
or 25 milliliters, which is about five teaspoons.
	MR. WHITFIELD.  And that is from each person?
	DR. MOLCHAN.  That is from each person during one spinal 
tap, yes.
	MR. WHITFIELD.  And you had a total of nine or so patients that 
you obtained 25 cc's from?
	DR. MOLCHAN.  There were more than that, and what was 
important about this study that I had done is we were able to get 
two spinal taps on people, one while they were taking medication 
and the other when not on the medication so we could compare.
	MR. WHITFIELD.  Okay.  So anyway, you used a small amount 
of this fluid for your research, and then you left the National 
Institute of Mental Health and went to FDA?
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  And then when you went over to the National 
Institute of Aging, a similar study came up and so you thought 
well, it will be great to go back and get to this spinal fluid?
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  And so you went to see Dr. Sunderland about 
the availability, I am assuming, or you talked to him or you made 
inquiry?
	DR. MOLCHAN.  Well, I inquired through one of my former 
NIMH collaborators originally who was still at the NIMH to 
inquire for me.  I followed up later with Dr. Sunderland by e-mail, 
I believe.
	MR. WHITFIELD.  Because he was the person--
	DR. MOLCHAN.  Responsible--
	MR. WHITFIELD.  --responsible--
	DR. MOLCHAN.  --for them.  Since he was the chief of the 
program there, the chief of the lab, yes.  
	MR. WHITFIELD.  And so were you able to obtain samples from 
him?
	DR. MOLCHAN.  He did send samples from eight of the 
patients, eight of the Alzheimer's patients, two of the normals, but 
only half a cc from each spinal tap, half a cc out of 25 cc's.  Now, I 
understand we didn't need a whole lot, but we would have liked a 
little more than a half of a cc, but when we asked for a little bit 
more or what happened to the rest of it, we just never got any good 
documentation of that.
	MR. WHITFIELD.  Okay.  So you never did find out how much 
they had?  Did they give you any explanation of where it was or 
anything?
	DR. MOLCHAN.  Just that some of it had been lost in freezer 
failures, freezer thaws, and that it has been a long time.  So no, 
nothing solid, nothing that made sense, because I knew the 
recordkeeping where this was done was very careful.  The spinal 
fluid is very important stuff for our research and Dr. Sunderland 
was always very careful about documenting how much we had and 
the research assistants would know in what freezers and what part 
of the--you know, whether it was collected late or early in the 
spinal tap.  It is very detailed information.
	MR. WHITFIELD.  So as you sit here today, do you know for a 
fact what happened to it?
	DR. MOLCHAN.  No.
	MR. WHITFIELD.  You still do not know, okay.
	DR. MOLCHAN.  No.
	MR. WHITFIELD.  Okay.  Now, you were at two institutes at 
NIH, and was there a protocol, a policy on the collecting, the 
storing, the tracing, the using of human tissue samples?
	DR. MOLCHAN.  Well, where I am now in the extramural 
program which deals with the university researchers, you know, 
helping to administrate and plan Alzheimer's research among the 
university community, whereas the intramural program does actual 
hands-on research, which I was in when I was in the National 
Institute of Mental Health.  At that point, yeah, I just don't know.  I 
wouldn't know about it.  I think you are talking about the 
intramural program specifically, and I didn't know when I was 
there.
	MR. WHITFIELD.  But you obviously were surprised that you 
were not able to obtain any information about the availability of 
spinal fluid?
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  And that you were not able to get the volume 
that you really needed to--
	DR. MOLCHAN.  Yes.
	MR. WHITFIELD.  --for your purposes?
	DR. MOLCHAN.  Yes, and I couldn't understand that.
	MR. WHITFIELD.  Now, did the people that you reported to at 
the National Institute of Aging, did you tell them about it and did 
they go to Dr. Sunderland about this issue, or was it just dropped?
	DR. MOLCHAN.  I tried to keep it within the National Institute 
of Mental Health, so I did mention it to my colleagues at Aging, 
but again, this was a separate time and place when I was at the 
NIMH.  It is an intramural program working specifically with Dr. 
Sunderland, so while I let them know about it, I didn't expect or 
ask them to do anything.  I told them I was following up with Dr. 
Insel and some other people.
	MR. WHITFIELD.  Now, at the time that you were at the Mental 
Health Institute, were you aware of scientists who had outside 
consulting agreements with--
	DR. MOLCHAN.  Yeah.
	MR. WHITFIELD.  So that was not anything unusual about 
having these consulting agreements?
	DR. MOLCHAN.  I don't have enough information to know how 
common or usual it was, but I know people did it and that there 
were ways to go about doing it.
	MR. WHITFIELD.  But you are not familiar with the disclosure 
requirements or anything like that, is that correct?
	DR. MOLCHAN.  For me with the intramural program at NIMH, 
these procedures have been evolving, these relationships between 
academia and industry, which I reiterate can be very positive if 
done in the right way.  So I wasn't involved in any myself, I was 
busy enough with my work at the NIH so I never looked into the 
rules of it seriously.
	MR. WHITFIELD.  Well, from the knowledge and experience 
that you have had working there and your professional occupation 
as a physician and scientist, would you agree with the statement 
that the protocol in place for tracking and collecting and using 
human tissues leaves something to be desired at NIH or do you 
have enough information?
	DR. MOLCHAN.  Well, just from my experience, it apparently 
did.  I mean, I hope this is an unusual--I think it is an unusual 
situation and otherwise, it is outside of my sphere of experience as 
to what an overall policy is there.  I would have to confer with 
other people.
	MR. WHITFIELD.  Now, tell me, who is Karen Putnam?
	DR. MOLCHAN.  Karen Putnam, she worked with Dr. 
Sunderland for many years as a research assistant.  She was, I 
believe--I don't know if she was a master's degree level.  She 
helped with everything from doing neuropsychological testing on 
people to inputting data to helping organize data, just kind of 
keeping track of things in general.  So she was a research assistant.
	MR. WHITFIELD.  And did you work with her on trying to 
obtain these samples?
	DR. MOLCHAN.  No.  Karen, as far as I knew, had left the 
NIMH a few years ago, though she may have still been doing some 
consulting.  I don't know.  I really wasn't in touch with them.
	MR. WHITFIELD.  Okay.  
	My time is expired.  Mr. Stupak?
	MR. STUPAK.  Thank you, Mr. Chairman.  Doctor, thanks for 
appearing today.
	You said Dr. Sunderland was your supervisor?
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  When you drew these samples, these cerebral 
spinal fluid, did he supervise that withdrawing of these samples?
	DR. MOLCHAN.  No.
	MR. STUPAK.  Okay.
	You indicated in a statement to the Chairman that sometimes 
your colleagues would step in and draw some of these samples for 
you, correct?
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  Okay.  Is there any way that Dr. Sunderland or 
someone else then could say that they sort of had ownership of 
these samples because they drew them?
	DR. MOLCHAN.  I have never heard of such a thing.  From what 
I understood when I left and otherwise, the samples belonged to 
the Government.  I don't think anybody would.
	MR. STUPAK.  So in this informed consent from these donors, 
did it identify the owner of the sample then being the NIH or 
NIMH?
	DR. MOLCHAN.  I would have to look at the language 
specifically, but again, that is such a broad question that we don't 
usually get into the details of.  I guess most of us just assume that it 
belongs to the NIH, the government.
	MR. STUPAK.  You said you left NIMH and when you left, was 
your study supposed to continue or did it stop or what happened 
there?
	DR. MOLCHAN.  I assumed it would continue.  When other 
doctors left, especially with clinical studies where patients had 
been involved, the studies were continued, the data analyzed and 
then written up and published.
	MR. STUPAK.  Sure.
	DR. MOLCHAN.  So I assumed that the people who were 
following on where my position was would continue it, but 
apparently that didn't happen.
	MR. STUPAK.  Do you know why your study stopped?
	DR. MOLCHAN.  I don't, no.
	MR. STUPAK.  Okay.
	DR. MOLCHAN.  Why it wasn't followed up, no.
	MR. STUPAK.  And you can't recite for us what the proper 
protocol or policy was on releasing any of these samples at NIMH 
then, the samples you drew?  Is there a certain procedure you have 
to follow before you release the samples?  Say you release it to 
Pfizer--
	DR. MOLCHAN.  The only samples I used were with a scientific 
collaborator within the NIH and to look at the samples as 
stipulated in the consent form to look at the effects of this drug, on 
and off the drug, so that was the only experience I had.  It was all 
within the NIH.  Other than that, I drew the samples and put them 
in the freezer and the research assistants would catalog them.
	MR. STUPAK.  And before you would release it to collaborative 
effort to work with somebody else, whether academia or whatever 
it is, you would know how much of the sample was sent, how 
much was requested--
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  --and the manner or method in which it was 
going to be used?
	DR. MOLCHAN.  Very much so.  It was very specific.  
Depending on what you measure, you need certain amounts.  I 
mean, sometimes you just need a tiny--you know, a drop, other 
times you might need as much as a few cc's, half a teaspoon.
	MR. STUPAK.  Okay.  When you were at NIH or the National 
Institute of Mental Health and you went over to the Institute on 
Aging, was it necessary or were you required to get any new 
consent forms from any of the donors as these samples were now 
being used in a different part of the agency than which was 
originally drawn for?
	DR. MOLCHAN.  Well, again, the samples were collected in an 
intramural program.  I am in the extramural program.  I don't know 
if--I knew what we were interested in was covered in the consent 
form, because we wanted to look at the effects of the drug on the 
paired samples.  And other than that we did academic circles, 
which in the past have been commonly done.  People would make 
an agreement and I will send you so much and do such and such on 
it, and then send you the information, send you the data.
	MR. STUPAK.  If you can answer this one, if Dr. Sunderland 
teamed up with Pfizer to do some research outside of NIH for 
Pfizer's benefit, when a sample is given from a donor, it is for 
research purposes, so could the research being done by Pfizer meet 
the definition in that consent agreement, or is the focus of the 
consent agreement from the donor that the ownership control use is 
for the government and not for outside?
	DR. MOLCHAN.  Well, there are mechanisms to have a 
pharmaceutical company or a biotech company do an assay for 
you, and in exchange for doing the assay--I mean, some of these 
are very expensive to do, so it actually can be very helpful.
	MR. STUPAK.  So the issue here really is not how the sample 
might have been used, whether internally or externally, but the lack 
of knowledge or--
	DR. MOLCHAN.  Well, their samples--the way they are 
collected, the reason was to look at the effects of this drug on some 
of the proteins, some of the things we could measure in the spinal 
fluid.  It is very specific to the actions of this drug, which has 
become of more interest recently in Alzheimer's research.  So that 
was very specific.
	MR. STUPAK.  But was that for all of your samples you drew 
was for a very specific purpose type of research?
	DR. MOLCHAN.  Well, for each protocol that we did at the time, 
we collected, as you have gathered, a lot of spinal fluid, and for 
each protocol we had, as I recall, a separate consent form.
	MR. STUPAK.  Okay.  I guess that is the best way to get a 
consent form is--okay.
	So it would have been unusual then to have it go outside of 
NIH in the protocol that you had established to get this donation, if 
you will?
	DR. MOLCHAN.  In a general sense or from my study?  I mean--
	MR. STUPAK.  The private gain companies in the mind of the 
donor, if you will.  What is their expectation of how the sample is 
going to be used I guess is what I am trying to get at.
	DR. MOLCHAN.  Right.  I would have to look at the exact 
wording on the consent form, but for the samples I drew, at least, 
they needed to be looked at in a paired way, on and off drug, to try 
to look at the effects of the drug.
	MR. STUPAK.  Sure, because you had a specific purpose that 
you were trying to test.
	DR. MOLCHAN.  Yes, and I recall that all protocol had a 
specific purpose.  Again, the consent forms have been evolving 
and IRB policies, and from what I recall, we needed to get a 
specific consent form for each protocol that we did, because a 
number of the protocols did involve drawing spinal fluid.
	MR. STUPAK.  Sure, but if I am a donor, how many cc's would 
you take?
	DR. MOLCHAN.  About 25.
	MR. STUPAK.  Okay, 25.  And I give permission and I give 25 
cc's, and you used 5 cc's, would that consent then restrict the 
remaining 20 cc's from going elsewhere, or was it only for your 
study?
	DR. MOLCHAN.  As long as it was sent with the understanding 
of what was in the consent form and set up through NIH-approved 
mechanisms, that I think would be reasonable.
	MR. STUPAK.  Okay.  I guess we will have to take a look at one 
of those consent forms.
	If you have more than what you are using, I guess another 
thing I am trying to arrive at, though, the remainder then is it 
restricted within NIH or can it be used outside of NIH?
	DR. MOLCHAN.  Oh, no.  In these things, we keep them in these 
big freezers which are very carefully regulated and backed up and 
controlled.  We keep some of what we collect, whether it is blood 
or spinal fluid, in hopes that an interesting assay--something 
interesting we will want to measure in the future will come along.  
So these things literally can be stored sometimes for decades.
	MR. STUPAK.  Okay.  In fact, in your testimony that you talk 
about the cerebral spinal fluid samples, which are highly valued, 
can be stored in freezers for years, and that you and your NIH 
colleagues had every reason to believe that they would still be 
available.  So it is your understanding that the samples which NIH 
investigators may have an interest in are generally preserved and 
made available for possible research along the lines in which they 
were drawn from, extracted from?
	DR. MOLCHAN.  That is a bigger area of policy than I am 
involved with, and again, I think some of those policies are being 
evolved and worked on.
	MR. STUPAK.  Okay.
	You also state in your testimony that "As research for 
Alzheimer's disease has progressed, the need for spinal fluid 
samples has increased as they may shed light on treatment options 
for this increasingly prevalent disease.  All available scientific 
resources are indeed to fight AD."  Could you elaborate further for 
the committee and for our understanding on how the loss of these 
samples and data could hamper further research or publications in 
the field of this research?
	DR. MOLCHAN.  Okay.  Are we talking about my specific study 
samples?
	MR. STUPAK.  Yes.
	DR. MOLCHAN.  Since another study was being planned by this 
Alzheimer's clinical trial consortium that I work with now, it 
didn't make sense that I had done a similar study and we couldn't 
get information from it.
	MR. STUPAK.  The data, in other words?
	DR. MOLCHAN.  That we couldn't get data.  I was able to give 
some of my experience as far the safety of the drug that we were 
using and everything in these Alzheimer's patients, and that was 
helpful, but it really would have been helpful to have more data on 
the effects on memory of what we were doing, as well as 
especially the spinal fluid because of being part of this new study 
that they want to do is to look at spinal fluid.  It is a big part of 
helping us to try to understand what is going on in Alzheimer's 
disease.  We can look at various measures in spinal fluid, how 
those measures react to a drug, for example, tell us something 
about what is going on, what is going wrong in Alzheimer's.
	MR. STUPAK.  If you know, you took samples from 25 subjects, 
right?
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  Of those 25 subjects, is there still partial of that 
25 cc's left for all 25 or are some of them gone, some of them have 
a little remaining?
	DR. MOLCHAN.  That is what I could never ascertain.  From 
what I understand, Dr. Sunderland sent the last of the samples to a 
collaborator of ours to measure something that the people planning 
this next study were interested in, that we were all interested in.  I 
never got a handle on what happened to most of it.
	MR. STUPAK.  Thank you.  Thank you, Mr. Chairman.
	MR. WHITFIELD.  Yes, sir.  Dr. Burgess, I think we have about 
8 minutes left in this vote.  Would you like to start asking some 
questions, or would you prefer to just wait and come back after the 
next votes?
	Why don't you go ahead and start, then?
	MR. BURGESS.  Very well.  Again, thank you for being here.
	I kind of know what a lumbar puncture is, but for the benefit of 
the uninitiated, maybe you could just quickly go through the 
procedure for us.
	DR. MOLCHAN.  Okay.  They really, for one thing, really don't 
hurt that much, and they--
	MR. BURGESS.  Well, the Chairman said they took three hours.  
Now, it may take the Chairman three hours, but it shouldn't take 
the rest of us.
	DR. MOLCHAN.  He would definitely need more.  We used to 
ask people--well--
	MR. WHITFIELD.  We could break now.
	DR. MOLCHAN.  Well, let me just go through the procedure.  It 
is a lumbar puncture or a spinal tap, and we withdraw some of the 
fluid that is in the sac that surrounds the brain and the spinal cord, 
and that has certain proteins in it that we are interested in.  So to 
withdraw some of this fluid, we introduce a needle in between a 
couple of vertebra in the lumbar spine in the back.  People are 
usually on their side when doing this, and the area is numbed up 
with some local anesthetic.  We insert the larger needle and 
withdraw about 25 cc's, which we allow to drip into however 
many--when I was doing it, about 10 tubes for use for various 
measurements.
	MR. BURGESS.  So it is a fairly invasive procedure?
	DR. MOLCHAN.  It is invasive.  It is very safe and it contributes 
very much to our work, but yes, it is invasive.  It is much more 
than drawing a blood sample.
	MR. BURGESS.  And in fact, 25 cc's is a fairly generous sample 
for someone who is used to doing them diagnostically.
	DR. MOLCHAN.  Yes.
	MR. BURGESS.  We would have normally obtained five to 10 
cc's.
	DR. MOLCHAN.  That is right, when they did them, um-hum.
	MR. BURGESS.  And perhaps a little bit greater risk for things 
like headache and other sequella after--
	DR. MOLCHAN.  That is not well-documented and we actually 
followed the incidents of headache, and especially in the older 
people, it is actually quite unusual, but that is the biggest side 
effect is headache.
	MR. BURGESS.  Now, Mr. Stupak was asking about whether the 
patients involved in these trials were informed about the lithium 
trial being concluded or ended and then these samples being used 
in newer trials.  To the best of your knowledge, there was no--that 
information wasn't given to the patients?
	DR. MOLCHAN.  No.
	MR. BURGESS.  Would that be unusual at NIH?
	DR. MOLCHAN.  Well, we had completed the data collection at 
least at that point.  We had done all the spinal taps we were going 
to do and the next step would have been to work with some 
laboratories to measure what we were interested in.  So as long as 
we were focusing on what was said in the consent form, measuring 
these paired samples on and off drug, then no, that would have 
been that.  If it was going to be used for anything else, I am sure 
there were procedures that would have to be--you would have to 
go through.
	MR. BURGESS.  Now, you had samples on 25 individuals in this 
particular study.  Can you give the committee any idea of how 
many tissue samples, which would include, of course, blood, urine, 
spinal fluid, other tissues, how many tissue samples are stored just 
in the intramural portion of the National Institute of Health at any 
given time?
	DR. MOLCHAN.  On an overall?
	MR. BURGESS.  Yeah, on an overall.
	DR. MOLCHAN.  Yeah, I have no idea.
	MR. BURGESS.  I know I don't either, but it has got to be a lot.
	DR. MOLCHAN.  Yeah, a lot is definitely what you are talking 
about of blood and urine specimens and cells.  A lot.
	MR. BURGESS.  And yet, we have heard it mentioned several 
times that there should be a centralized databank, if you will, of all 
of the tissue stored at NIH.  Do you think that is even technically 
feasible?
	DR. MOLCHAN.  Well, it depends how central.  With our 
information technology now, and I know for some projects that we 
have in the university world that when we collect samples we do 
want to know what we are collecting and make them available to 
researchers to maximize their use.  So these databases are starting 
to be built up.  Again, it is a big coordinating effort using our 
information technology.
	So they are underway and I don't know where they are in the 
intramural program with that at this point.
	MR. BURGESS.  But in the year 2006, that is just kind of 
beginning?
	DR. MOLCHAN.  Yes.
	MR. BURGESS.  In 1996, that probably would have been 
unheard of.
	DR. MOLCHAN.  Yes, most likely.  Yes.
	MR. BURGESS.  The fact that there wasn't any centralized 
database for you to go to to find where your samples were, that 
wasn't necessarily unusual?
	DR. MOLCHAN.  No.
	MR. BURGESS.  Someone else doing research on diabetes that 
had blood sugar samples might have the same trouble?
	DR. MOLCHAN.  Yeah, I would be surprised, but yeah, not that 
I know of.
	MR. BURGESS.  Whose responsibility was it to keep those 
samples safe and retrievable during your tenure there and then after 
you left, where did that responsibility get assigned?
	DR. MOLCHAN.  From what I understand and from what I 
thought, it resided with each laboratory chief who was in charge of 
the certain projects under which the samples were collected.
	MR. BURGESS.  And that laboratory chief in your section would 
have been?
	DR. MOLCHAN.  Dr. Sunderland.
	MR. BURGESS.  Can you just tell us a little bit about the lithium 
study without giving away any trade secrets?
	DR. MOLCHAN.  Yes.  There is, actually, one drug company 
doing a similar study now, too, but--
	MR. BURGESS.  I mean, lithium doesn't cure Alzheimer's.
	DR. MOLCHAN.  No, it does not.  There has been some 
interesting data in the past few years showing that in cell studies 
and in mice studies that lithium seems to have some effects that 
hold off degeneration of neurons, including inhibiting the amyloid 
plaques and the neurofibrillary tangles.  It is very interesting 
because lithium has never been thought of that way.  So with these 
laboratory studies, it has become more of interest to use to see if 
we could give lithium and then see what happens, for example, in 
the spinal fluid to levels of amyloid and to levels indicating the 
fibrillary tangles to see if we should target drug development along 
those lines.
	MR. BURGESS.  And that is important, because even though you 
are not curing Alzheimer's disease, even if you can slow down the 
course a little bit, that is important as well, isn't it?
	DR. MOLCHAN.  As far as the study we were doing, we were 
trying to find out more.  We know lithium and when we use drugs 
in this way that they work under certain mechanisms, inhibit 
certain enzymes and so then we test what we can measure in the 
spinal fluid and from that, we can ascertain whether that enzyme, 
for example, is inhibited or not and would we want to work to dis-
inhibit it to help Alzheimer's disease, things like that.  So it is 
more mechanism.
	MR. BURGESS.  Do you know, do we know, does the committee 
know, is it available in our report or do you know the information 
about what were the samples used for, the samples that were 
diverted away from the NIH?  Do we know what those were used 
for?
	DR. MOLCHAN.  I don't know.
	MR. BURGESS.  So then to the best of our knowledge, there 
hasn't been any published data about--
	DR. MOLCHAN.  Well, there was not after I left the institute, the 
study wasn't followed up, so no, there were no published data on 
the effects of lithium on these samples, which they were meant for.
	MR. BURGESS.  Were there any other studies of any type then 
done on these samples after they were diverted--
	DR. MOLCHAN.  That is what I don't know.
	MR. BURGESS.  --from your lab?
	DR. MOLCHAN.  I don't know.
	MR. BURGESS.  So we don't have that information?
	DR. MOLCHAN.  I don't have it.  I don't know if anybody--
	MR. BURGESS.  Does anybody have that information?
	DR. MOLCHAN.  The committee staff may have some of it.
	MR. WHITFIELD.  We have some of that information which I 
can talk to you about as we go over--
	MR. BURGESS.  All right.
	MR. WHITFIELD.  Dr. Burgess, we have a minute to get over to 
vote, so when we come back we will recognize you for another 2 
minutes.
	MR. BURGESS.  You are too kind, Mr. Chairman.  I will delay 
further questions with that in mind.
	[Recess]
	MR. WHITFIELD.  The hearing will resume, and at this time, I 
will recognize Dr. Burgess for his remaining two and a half 
minutes.
	MR. BURGESS.  Thank you, Mr. Chairman.  
	Dr. Molchan, did Dr. Sunderland ever talk to you about what 
happened to the samples or the research data from your study?
	DR. MOLCHAN.  Just in e-mails and phone calls.  I got the 
information as related that the samples that he sent to our 
collaborating scientists was all that was left; that the rest was lost 
in freezer failures.  He did indicate, I believe, that they had been 
used in--well, I would have to look at the records for sure, but from 
what I could get at the time, he gave me everything that was left.  
He mentioned some freezer thaw problems where samples were 
lost.  As far as some data, he mentioned it is old data and 
everything--he seemed to be under the impression that it was 
published data, which it wasn't.
	So I got an incomplete response as to what happened.
	MR. BURGESS.  And just to reiterate for the committee, why 
were you unable to complete the lithium study?
	DR. MOLCHAN.  I had to leave the NIMH.  My time was up 
there and I had to leave, and at the time wanted to stay in the area.  
I was committed to stay in the Bethesda area and wanted to stay in 
the public health service, so I transferred to the FDA.
	MR. BURGESS.  Was there no one in the lab that you sort of 
signed out to and said this is what I am working on, the taxpayers 
have invested this much money in this lithium study.  Would you 
please continue it?
	DR. MOLCHAN.  No.
	MR. BURGESS.  Would that be common to do that within a 
research lab if someone had reason to leave the lab?
	DR. MOLCHAN.  Well, when we were there I was on staff at the 
NIH clinical center, so I was no longer a fellow or anything, but 
again, the lab chief--it would have been unusual.  That just wasn't 
part of the procedure.  The lab chief had the responsibility for 
studies ultimately.
	MR. BURGESS.  Was the lithium study something that was 
assigned to you in the lab, or was this a concept that you had 
yourself that you--
	DR. MOLCHAN.  It was something that I wanted to do as an 
independent project.  I had the idea based on some actual 
laboratory research that I had done years ago.
	MR. BURGESS.  But other people in the lab you discussed the 
lithium study with, had you convinced anyone that this was 
worthwhile research, or did everyone else--
	DR. MOLCHAN.  I thought so.  I thought Dr. Sunderland, as 
well as at the time, the overall branch chief, and it went through, of 
course, the IRB committee of the NIMH, part of which debates 
whether it is a rational study to do, if it is worth doing, so yes.
	MR. BURGESS.  Does the committee need to be concerned that 
there are other studies that are just sort of dropped in mid-stride as 
people come in and come out of the NIH?
	DR. MOLCHAN.  Well, for clinical studies, I don't think there is 
any good--I mean, there are a lot of studies started by post-
doctorals, perhaps, that some may not be followed up.  When 
someone leaves, I guess many times they go to a university--to 
another laboratory and bring data with them, so that happens.  And 
as far as an overall plan for what happens, that is beyond my 
experience.
	MR. BURGESS.  Well, you said in your testimony since 
Congress has shown an interest in this matter, some progress has 
been made.  Can you elaborate on what you mean by "some 
progress"?
	DR. MOLCHAN.  Well, the NIH has instituted some trans-NIH 
policies on trying to better keep track of these samples, for one 
thing, and I was also able to get some additional data that I needed, 
just some basic demographic data on the subjects that we had the 
spinal fluid on so I can include that in a publication.
	MR. BURGESS.  Very well.  Mr. Chairman, you know, I would 
just point out that we do talk about having some sort of centralized 
databank and I think that is a wonderful thing, but you know, in 
1996, 1997, I don't know how feasible that was and in my 
experience in working in labs, I mean, you have got a refrigerator 
full of stuff and not everyone knows what all is contained therein 
and the importance thereof.  I don't mean that that is right, if it 
sounds like the NIH is well on the way to remedying and rectifying 
that problem, but I just wonder about our ability to draw 
conclusions on a practice from 10 years ago when quite frankly, 
the computer database technology just may not have existed to 
keep track of what realistically may have been several million 
tissue specimens contained at the NIH.
	I yield back.
	MR. WHITFIELD.  Thank you, Dr. Burgess, and of course, that 
is what we are going to be focused on as we move forward, and 
tomorrow we will have some other witnesses, including the 
Director of the National Institute of Mental Health.
	At this time, I recognize Mrs. Blackburn for 10 minutes.
	MRS. BLACKBURN.  Thank you, Mr. Chairman.  Dr. Molchan, 
thank you, and thank you for your patience with allowing us to go 
over and vote and then come back.  
	I will tell you that I am not a physician like Dr. Burgess, and 
not been involved in any of the research projects like he has, but I 
am very typical of a lot of Americans in that I have lost a loved 
one to Alzheimer's.  And through that, have watched some of the 
research and some of the progress and some of the--I guess you 
would call them near-misses in your community.  And I have 
found this really quite interesting to read through the materials for 
this hearing, and I appreciate very much your stepping forward, 
and working with us.  You are making the information aware, but I 
don't have to tell you, whether it is the NIH or any number of other 
Federal agencies, there is an arrogance that exists within the 
bureaucracy, a lack of respect that does exist for, I think, this body 
and for our oversight and for our desire to be certain that the 
taxpayers' money is appropriately spent.  And I think it was quite 
appropriate that the Chairman of this committee, Mr. Barton, 
mentioned trust when he made his opening remarks, because it is a 
loss of trust in the NIH and how they spend their funds, and as we 
have the head in here, it is something that we are going to be 
discussing and visiting with him about.
	A couple of questions I want to go back to, and I feel like I 
have got a page of notes here as you have talked and given your 
comments today.  You mentioned that the comment was made you 
were told that you didn't find out exactly what had happened, that 
the loss of the samples was attributed to freezer loss and that 
nothing seemed to make sense.  Now, who was it that told you 
that?  Was it Dr. Sunderland or someone that worked with him?
	DR. MOLCHAN.  Dr. Sunderland, yes, in e-mails, yes.
	MRS. BLACKBURN.  Okay.  So he himself--
	DR. MOLCHAN.  Yes.
	MRS. BLACKBURN.  --told you that, and you know that didn't 
seem right, because you know you are not going to lose that much 
through freezer burn, if you will--
	DR. MOLCHAN.  Correct.
	MRS. BLACKBURN.  --or--
	DR. MOLCHAN.  Or whatever reason.  I just know how 
carefully we kept track of them when I was there.
	MRS. BLACKBURN.  Okay.
	DR. MOLCHAN.  And if there was a freezer failure, there would 
have been some documentation of that, dates and which samples 
were lost, and there is just nothing specific.
	MRS. BLACKBURN.  And I would imagine that the NIH with 
these freezers runs them from an operational standpoint that you 
have a generator backup so that you are never down, and you have 
got a flush point to move over in case you were to lose power, you 
would immediately go to a generator?
	DR. MOLCHAN.  I haven't dealt with these freezers for a long 
time, but they are quite technical and backed up and--
	MRS. BLACKBURN.  As I would imagine and we would expect.
	DR. MOLCHAN.  A record of the temperature every 24 hours 
and--
	MRS. BLACKBURN.  Okay.  When I had stepped out of the 
room, I think that you were mentioning to our Chairman the 
material transfer process.  Were you giving a description of what 
that material transfer process was?
	DR. MOLCHAN.  I was probably explaining that I really--from 
my job back then at NIMH and my job now--I really haven't dealt 
with those, so I would have to--there is a whole staff at NIH now 
to help people deal with those, because it is getting more complex.
	MRS. BLACKBURN.  Okay.  Now, Mr. Chairman, do we have 
something in writing that describes for us the process by which 
samples would be transferred within NIH and then to actually 
leave the jurisdiction of NIH?  Do we have that in writing?  Is 
there a document that we have received or should we request that 
from our witness?
	MR. WHITFIELD.  Just a minute.  I will ask our counsel here.
	MRS. BLACKBURN.  And at the same time, do they have in 
writing a review process by which they would go back and review 
why a sample was requested?
	MR. WHITFIELD.  We have material transfer agreements.  We 
have copies of that, and it is in the binder.  It is Exhibit #2.  Then 
we have Exhibit #38 is NIH technology transfer in U, an 
explanation of that, and then of course, tomorrow, as you know, 
we are going to have a number of panels here, three panels and 
everyone will be from NIH or has been.  We will be able to get to 
that in more detail then.
	MRS. BLACKBURN.  Okay. 
	Dr. Molchan, I think you are familiar with those transfer 
processes, and would you agree that those and that the review, is it 
substantial, does it give you enough coverage, is there enough 
review if samples are requested?
	DR. MOLCHAN.  The samples of materials transfers?
	MRS. BLACKBURN.  Yes.
	DR. MOLCHAN.  I really have not dealt with them in any detail 
so I can't--
	MRS. BLACKBURN.  Okay.  
	Let me move on then.  Dr. Sunderland in his relationship with 
Pfizer, would that be--from your vantage point, would you see that 
as being a normal or abnormal relationship for a researcher from 
NIH?
	DR. MOLCHAN.  Again, I don't have the details of the 
relationship, and haven't been in contact with Dr. Sunderland in 
years.  I can't comment since I don't know.
	MRS. BLACKBURN.  Just from other researchers.  And then also, 
is it a normal practice for NIH researchers who are working on a 
project to go and speak and be paid for the speeches for different 
pharmaceutical companies and then to be invited into relationships 
with those companies?
	DR. MOLCHAN.  As far as I know, it is not, and again, it never 
entered my area of activity or interest, especially since I was at the 
Food and Drug Administration, so I was totally out and divested in 
everything.
	MRS. BLACKBURN.  Okay.  And then do you know if there is an 
oversight process and who would be involved in that process that 
would be checking the relationships with the NIH researchers?
	DR. MOLCHAN.  I don't know.
	MRS. BLACKBURN.  And you never had anyone come to you 
and question a relationship that you had?
	DR. MOLCHAN.  I haven't been involved in any relationships, 
you know, since I have been in the Government, especially since I 
went through the FDA. 
	MRS. BLACKBURN.  Okay.
	DR. MOLCHAN.  It is just definitely not allowed there.
	MRS. BLACKBURN.  So while you were aware of others that 
were paid consulting fees--
	DR. MOLCHAN.  Yes.
	MRS. BLACKBURN.  --had consulting agreements, you had none 
of your own?
	DR. MOLCHAN.  No.
	MRS. BLACKBURN.  Okay.  All right.
	Let me ask you this, because I thought your comments to Dr. 
Burgess were interesting when you were talking about the lithium 
study and it just dissipated.  How much money did you spend on 
that study through your process?
	DR. MOLCHAN.  Well, I didn't have a budget myself, and what 
it cost from the budget of the laboratory I was in, Dr. Sunderland's 
group and at that point, our branch chief, Dr. Murphy, they would 
have the numbers on that.  I don't know what the cost was back 
then.  I just don't, since I didn't have my own budget.
	MRS. BLACKBURN.  Okay.
	Well, thank you, and Mr. Chairman, I will yield back.
	MR. WHITFIELD.  Thank you, Ms. Blackburn.
	Mr. Molchan, Mr. Stupak in either his opening statement or 
questions, mentioned that around $6 million was the estimated cost 
of collecting these samples.  Do you know how that figure was 
determined or calculated?
	DR. MOLCHAN.  He was talking, I think, of more samples than 
just involved in my study--
	MR. WHITFIELD.  Right.
	DR. MOLCHAN.  --so I don't know.
	MR. WHITFIELD.  Okay.
	And now, what makes spinal fluid so valuable?  Just the 
process of what you have to go through to get it?
	DR. MOLCHAN.  It is not the easiest thing to collect because 
you have to have special equipment, you have to have special 
storage for it.  A lot of people, especially in this country--it is a 
common medical procedure done in many hospitals for many 
different reasons, and it is very safe, but still I guess the vision of 
having a needle placed into your back doesn't bode well for most 
people, so we have to convince people that it is worth it.  The 
spinal fluid itself bathes the brain, some of the chemicals in the 
brain.  It is the closest thing you can get to the brain without taking 
a piece of the brain.
	MR. WHITFIELD.  Absolutely.
	I also want to ask unanimous consent that we enter into the 
record a form that is the consent to participate in a clinical research 
study, and this actually is a form that has you listed as one of the 
principal investigators.  I don't think we have a copy of this for our 
record, so I would ask unanimous consent that we enter that into 
the record.
	[The information follows:]



	MR. WHITFIELD.  At this time, Chairman Barton, would you 
like to ask some questions of this witness?
	CHAIRMAN BARTON.  Am I the last to question here?
	MR. WHITFIELD.  Yes, sir.
	CHAIRMAN BARTON.  Okay.  
	I have some questions.  They are going to be a little bit more 
generic.
	Does the administration at NIH share the committee's concern 
about lack of a centralized tracking system for human tissue 
sample collection and maintenance?
	DR. MOLCHAN.  You would have to--again, I am not at that 
level of policy and administration, so I don't--from what I have 
seen in e-mails, there is more and more interest in it in general in 
the research community.
	CHAIRMAN BARTON.  Well--
	DR. MOLCHAN.  The details of NIH, since that is not my 
purview--
	CHAIRMAN BARTON.  Well, let me rephrase the question.
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  Do you share the concern?
	DR. MOLCHAN.  Based on my recent experience, understanding 
that these samples were collected several years ago, I think things 
are getting better, and I have seen movements towards policies and 
working groups being put in place to start to get some more 
consistent policies.
	CHAIRMAN BARTON.  All right.  
	What knowledge do you have of these spinal fluid samples: 
Have you been told what happened to the spinal fluid samples that 
you were so interested in that you couldn't get access to?
	DR. MOLCHAN.  I guess just from two sources.  From Dr. 
Sunderland, which I just mentioned, that there weren't anymore 
left.  Some of them were lost in freezer thaws, and then from what 
I understand, the committee found that some of them had gone to 
Pfizer from the NIMH.
	CHAIRMAN BARTON.  Well, 95 percent that according to 
committee staff briefings were unused, how many of those, in your 
opinion, have been misused or inappropriately sent outside of 
NIH?
	DR. MOLCHAN.  That is what I can't have any documentation 
of or try to ascertain but never got an answer, other than general 
answers that they are not there anymore, they were lost.
	CHAIRMAN BARTON.  You are okay with that?
	DR. MOLCHAN.  Well, I wasn't okay with that.  That is how we 
ended up here.
	CHAIRMAN BARTON.  Do you have a solution?
	DR. MOLCHAN.  From my purview, I went through channels for 
a number of months and then expressed my concerns to the 
committee, and had done everything I felt I could do.  I didn't 
think I was going to get an answer myself, and thought perhaps the 
committee might.
	CHAIRMAN BARTON.  You have hardly answered--I gave you a 
question right off the bat where you could say yes, we need a 
centralized system for monitoring and tracking our human tissue 
samples, and you basically told me that was outside your area of 
expertise; that you really didn't have a position on it.
	DR. MOLCHAN.  Well, it depends on a lot of details on that.  I 
know that when we get into these policy things and at what level, it 
is a complex question and I think--
	CHAIRMAN BARTON.  It is not that complex.
	DR. MOLCHAN.  I mean, in a general sense--
	CHAIRMAN BARTON.  If you don't have a system in place--
	DR. MOLCHAN.  Right.
	CHAIRMAN BARTON.  --to back it across an agency, you are 
depending on pure faith that everybody--
	DR. MOLCHAN.  Of course, there are some systems in place.  
Again, how--and it is getting more consistent across the various 
institutes.  I just don't know details of that since I am not--
	CHAIRMAN BARTON.  If you were in charge of the NIH, what 
would you change about the current system for human tissue 
sample collection, storage, and inventory, if you were in charge?
	DR. MOLCHAN.  Well, again, the NIH is a big place and I am 
just one tiny piece of it, and these samples came from 10 years 
ago.  So yes, there needs to be careful documentation of who these 
samples were taken from and when and for what and the consents, 
where they go, what data results from them.  Hopefully it will be 
shared among investigators, and I hope a lot of that is underway.  I 
just can't, under oath, I guess I am just not comfortable going into 
too much detail because it is beyond my experience.
	CHAIRMAN BARTON.  So you have no recommendation?
	DR. MOLCHAN.  Well--
	CHAIRMAN BARTON.  What did you expect the committee to do 
when you contacted us?
	DR. MOLCHAN.  Well, I know that there has been some 
progress made, that there are trans-NIH--
	CHAIRMAN BARTON.  Is somebody at NIH pressuring you to 
hold back?
	DR. MOLCHAN.  No.
	CHAIRMAN BARTON.  Are you under any kind of threats?  I 
have given you every opportunity to just absolutely tell us what 
you think needs to be changed, and you have resolutely refused.  
That is fine.  You don't have to, but my gosh--
	DR. MOLCHAN.  I just don't know--
	CHAIRMAN BARTON.  --you are the person who came to us and 
said we have got a problem.  You would think you would have 
some ideas about how to solve it, other than just say--
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  --it is outside of my area of expertise.
	DR. MOLCHAN.  NIH is a big place and there are lots of 
different labs and different institutes, and I just have no idea of the 
policies in those places.  It is outside of my purview, but yes, of 
course we need systems to track these things.
	CHAIRMAN BARTON.  How about some penalties if you abuse 
the tracking system?
	DR. MOLCHAN.  I would hope--
	CHAIRMAN BARTON.  Do you think it is appropriate that some 
of your spinal fluid samples went to Pfizer?
	DR. MOLCHAN.  Not unless they were used as indicated in the 
consent form and from what I have gathered, they were not, so no.
	CHAIRMAN BARTON.  Do you think Dr. Sunderland was truthful 
and honest with you when you inquired about those samples?
	DR. MOLCHAN.  Well, since I never got a complete answer and 
we all like to see data evidence, no, that is why I went further up 
the chain.
	CHAIRMAN BARTON.  All right.  Do you believe at least said 
that he was not truthful and open with you?
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  What would he have had to have done to 
have met your requirement that he didn't do?
	DR. MOLCHAN.  Just document, just tell us what happened to 
the rest of them, whether it was really in freezer failures--that large 
volume--again, from the careful documentation I knew went on in 
that laboratory on these types of things, I would have liked to see 
some documentation of what happened and when and there was 
just nothing like that.
	CHAIRMAN BARTON.  But to your knowledge today, there is not 
an acceptable accounting of those samples that were unused, is 
there?
	DR. MOLCHAN.  Correct.
	CHAIRMAN BARTON.  Are you okay with that?
	DR. MOLCHAN.  No, I have never been okay with it, and I have 
done what I can do--
	CHAIRMAN BARTON.  If you were Mr. Whitfield or Mr. Stupak, 
the Chairman and Ranking Member, would you insist on an 
accurate accounting of those samples?
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  Okay.
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  I guess, Mr. Chairman, that is all the 
questions I have.
	MR. WHITFIELD.  Thank you, Mr. Chairman.
	Mr. Stupak, I understand you have a few additional questions?
	MR. STUPAK.  Yes.  Doctor, if I may, to your right there is your 
consent form.  You see it right there?
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  And I note first that the form appears to be dated 
October of '84, so that form is already 22 years old.  Have they 
updated the form since then, do you know?
	DR. MOLCHAN.  These are all 1984.
	MR. STUPAK.  Let me further identify, this is your evaluation of 
lithium treatment in dementia and Alzheimer's patients.
	DR. MOLCHAN.  That is right.
	MR. STUPAK.  This is your--
	DR. MOLCHAN.  And these are the details of the consent form 
that I asked them to sign, that is right.
	MR. STUPAK.  So you don't know if they have updated this 
consent form since then?
	DR. MOLCHAN.  The template I guess came from 1984, and I 
don't know.
	MR. STUPAK.  Okay.  Let me ask you this, because I asked a lot 
of questions about consent form and things like that.  
	The consent forms only apply to your specific lithium study, so 
it raises at least two questions with me.  Could the samples then be 
used for the consortium study on lithium use in Alzheimer's 
patients--or research, I should say, and the consortium, I mean with 
the University of Pittsburgh.  Do you believe that based on this 
informed consent, those samples could be used with the 
consortium at the University of Pittsburgh?
	DR. MOLCHAN.  Since we were using samples on and off the 
drug of interest to see what the effects were, yes.
	MR. STUPAK.  Okay.  Then how could such a specific consent 
form--because I do agree that it is pretty specific--cover transfer to 
Pfizer for a non-lithium study?
	DR. MOLCHAN.  It does not, from what I can see.
	MR. STUPAK.  And then there is no way you could bend that to 
make it cover--
	DR. MOLCHAN.  No.
	MR. STUPAK.  --Pfizer, unless they are doing something with 
lithium, right?  That is your understanding?
	DR. MOLCHAN.  Yes.
	MR. STUPAK.  Okay.
	DR. MOLCHAN.  That is right.  To look at the effects of the 
drug, yes.
	MR. STUPAK.  Correct, because you deal with a number of the 
neuro-transmitters there, because--right?  And you are looking to 
see how lithium acts on it?
	DR. MOLCHAN.  That is right, yes.
	MR. STUPAK.  Help me out here, acetocholene?
	DR. MOLCHAN.  Acetocholene.
	MR. STUPAK.  Acetocholene is a brain chemical that serves as a 
messenger or neuro-transmitter in the brain and lithium does affect 
that, correct?
	DR. MOLCHAN.  What we have been able to see in more 
Alzheimer's specific measures having to do with the amyloid that 
is deposited in the brain, things like that.
	MR. STUPAK.  Right, but that is spelled out pretty well in this 
study?
	DR. MOLCHAN.  But still we are looking at the effects of 
lithium on it to see if we should, again, go in the direction of a 
drug mechanism in the way that lithium works, if we should try to 
develop something similar with not so many side effects, for 
example.
	MR. STUPAK.  Thank you.  I have nothing further, Mr. 
Chairman.
	CHAIRMAN BARTON.  Mr.--
	MR. WHITFIELD.  Yes, Mr. Chairman?
	CHAIRMAN BARTON.  I have just one or two more questions.
	Dr. Sunderland, who has been subpoenaed to testify before this 
same subcommittee tomorrow, I believe, we were led to believe is 
going to plead the Fifth Amendment against self-incrimination, but 
he may not, but we are led to believe that.  In your view, do you 
think that is an appropriate thing for him to do, in terms of the 
jurisdictional issues at NIH and responsibilities to be open and 
transparent in dealings with the public?
	DR. MOLCHAN.  I think NIH scientists should be as open and 
transparent with the public as possible, and from my experience, 
generally they are, so yes, they should be.  And as far as him 
taking the Fifth, I don't know his full situation.  I am not a lawyer, 
so I can't comment on that.
	CHAIRMAN BARTON.  Did he ever indicate to you when you 
were trying to get answers on these same questions that you should 
just mind your own business or bug off or it wasn't your 
responsibility anymore?
	DR. MOLCHAN.  Not from him.  I got that impression from the 
NIMH director.
	CHAIRMAN BARTON.  And who is that person?
	DR. MOLCHAN.  Dr. Insel.  That was from an e-mail where he 
indicated that I should, you know--Dr. Sunderland is occupied with 
plenty of other things right now.  Please leave him alone.
	CHAIRMAN BARTON.  I understand how busy that fellow can 
be.
	DR. MOLCHAN.  Yeah.
	CHAIRMAN BARTON.  What is the general loss associated with 
freezer melting or whatever the technical term is?  Would that 
normally be like one or two percent or 40 or 50 percent?
	DR. MOLCHAN.  It depends on the sample.  I mean, in some of 
these freezers we have whole brains, for example, and it depends 
on what you are measuring and it depends on the sample.
	CHAIRMAN BARTON.  Well, in general, wouldn't you expect 
that high value human tissue samples, especially like spinal fluid 
that are difficult to obtain, that there would be some fairly 
elaborate--
	DR. MOLCHAN.  There are.
	CHAIRMAN BARTON.  --mechanisms and fail-safe--
	DR. MOLCHAN.  At the time I left the NIMH, there were quite 
elaborate systems of backup--
	CHAIRMAN BARTON.  You shouldn't have a high percentage of 
loss--
	DR. MOLCHAN.  Correct.
	CHAIRMAN BARTON.  --just from something like that?
	DR. MOLCHAN.  Right.  There was backup and alarms, people 
would be called if there was a failure.
	CHAIRMAN BARTON.  Okay.
	DR. MOLCHAN.  Or if any temperature aberration, you know.
	CHAIRMAN BARTON.  Staff wants me to ask this question.  
What is the average cost per human subject in an Alzheimer's 
disease clinical trial?  Average cost per human subject in an 
Alzheimer's disease clinical trial.
	DR. MOLCHAN.  For the Alzheimer's consortium that we deal 
with at the National Institute on Aging, we have been able to 
calculate that, and we have records.  What did we say, about 
$12,000 per subject.  Now, it depends on the length of the trial and 
how many tests you do, things like that, but on average for the 
trials we have done at NIA, it has been $12,000 per subject for 
what they call direct costs, and it is much more than that when you 
look at total costs when you are including the research 
infrastructure and data storage and analysis and other things 
involved most specifically with research.
	CHAIRMAN BARTON.  What percentage of that is the collection 
of spinal fluid, do you know?
	DR. MOLCHAN.  No.
	CHAIRMAN BARTON.  Just generally, would it be big 
percentages, little percentage?
	DR. MOLCHAN.  Well, when we collect spinal fluid--we haven't 
done it very routinely in studies in the past several years.  We used 
to, and then we fell away from it, and now with the importance of 
it, we are including it in many more studies now.  I just know, for 
example, for the lithium study that is being proposed for this 
consortium, the cost is estimated to be $17,000 per patient.
	CHAIRMAN BARTON.  Well, if Dr. Sunderland used some of 
these spinal fluid samples that we don't know what happened to, 
we know that 528 subjects were used in his Pfizer project, so based 
on your knowledge of the spinal fluid sample volume, how much 
of that missing spinal fluid would be needed for 528 subjects in 
this Pfizer project study?
	DR. MOLCHAN.  It would--again, how much spinal fluid would 
he need for--depend on, again, what he was measuring and lots of 
variables.
	CHAIRMAN BARTON.  But I mean, again, I am not asking you to 
be accurate to the milliliter.
	DR. MOLCHAN.  Yeah.
	CHAIRMAN BARTON.  But would it have taken half of the spinal 
fluid or--
	DR. MOLCHAN.  Oh, from a spinal tap?
	CHAIRMAN BARTON.  Yeah.
	DR. MOLCHAN.  Most of these assays take just a tiny amount, 
2, 3 cc's, usually much less.  Two or 3 cc's, say, out of the 25.  
Whether there are some tests out there that need more, I am not 
sure, but usually it is just a fraction of what we collect during a 
spinal tap, yes.
	CHAIRMAN BARTON.  I mean, but if he--and I am not saying 
that he did, okay, this is purely hypothetical.  If he totally used 
these spinal fluid samples that are unaccounted for for this 538 
subject project at Pfizer, would that have consumed one-third, one-
fourth, one-fifth--
	DR. MOLCHAN.  I don't know, since I don't know all of his 
projects that he was doing with Pfizer.
	CHAIRMAN BARTON.  But it would take at least 3 cc's per 
subject?
	DR. MOLCHAN.  I would think, yes.
	CHAIRMAN BARTON.  When you take a spinal tap from an 
individual, how much fluid do you get out of that?
	DR. MOLCHAN.  Generally around 25 cc's.
	CHAIRMAN BARTON.  So it would take at least one-eighth.
	DR. MOLCHAN.  It is possible, yes.
	CHAIRMAN BARTON.  Just mathematically we would say--
	DR. MOLCHAN.  Yes.
	CHAIRMAN BARTON.  --he used an eighth of--that would be a 
fair--
	DR. MOLCHAN.  That is a fair estimate.
	CHAIRMAN BARTON.  --guess?
	DR. MOLCHAN.  Yeah, you don't like to put all your spinal 
fluid in one place, I hope, or send it to one collaborator, and you 
often want to keep specimens like that that are non-renewable on 
reserve for future interesting possibilities.
	CHAIRMAN BARTON.  Okay.
	MR. STUPAK.  Mr. Chairman, if I may?
	CHAIRMAN BARTON.  Sure.
	MR. STUPAK.  In the type of research that Pfizer was doing, I 
understand it is proteomics?
	DR. MOLCHAN.  Proteomics, yes, looking at--
	MR. STUPAK.  Does that take more fluid than a normal--
	DR. MOLCHAN.  That is what I--since I am not a laboratory 
assay person, I think some of those take a little more, maybe a few 
cc's, but I don't know really details of which proteins they are 
measuring, so I don't know.
	MR. STUPAK.  But it is fair to say in this type of study or 
research you are conducting, they would have needed more than 
normal of the fluid?
	DR. MOLCHAN.  More than normal as opposed to--
	MR. STUPAK.  In the other testing, compared to the lithium test.
	DR. MOLCHAN.  I think they do need--from what I understand, 
you need a fairly large volume compared to measuring some other 
things that were routinely measured.
	CHAIRMAN BARTON.  Pilfered.
	MR. STUPAK.  Thank you.  Yield back to the Chairman.
	CHAIRMAN BARTON.  My final question.  I asked you earlier 
what the cost per subject, and you said between $12,000 and 
$17,000.  We really didn't get a good estimate if you know what 
the spinal fluid cost of that was, but let us assume that it is one-
eighth.  That would be about $1,500 per subject times 528 subjects, 
that is close to three-quarters of a million dollars that was used 
inappropriately.
	DR. MOLCHAN.  Well, the 538 came from a number of different 
protocols, the 538, and I don't know what was in all those consent 
forms, for one thing.
	CHAIRMAN BARTON.  If three-quarters of a million dollars of 
tissue samples were used in a privately funded study, somebody 
should sign off on that and the Government should be reimbursed 
for that cost.  Do you agree with that?
	DR. MOLCHAN.  Yes, certainly.
	CHAIRMAN BARTON.  Okay.  I yield back, Mr. Chairman.
	MR. WHITFIELD.  Thank you, Mr. Chairman.
	That concludes this section of this hearing, and Dr. Molchan, 
we appreciate your being with us today.  
	Tomorrow, we will have some witnesses that hopefully will be 
able to be more specific on suggested protocols as we seek ways to 
guarantee the tracking of these human tissue samples.  Tom Insel, 
who is the director of National Institute of Mental Health, is one of 
the witnesses.  The Deputy Director for Intramural Research, 
Michael Gottsman, will be here, in addition to Dr. Trey 
Sunderland, Dr. Karen Putnam, and Dr. David Friedman. 
	So we will recess this hearing until tomorrow at 10:00 a.m., 
and Dr. Molchan, thank you again for being with us.
	[Whereupon, at 4:52 p.m., the Subcommittee was recessed, to 
reconvene the next day at 10:00 a.m.]



              HUMAN TISSUE SAMPLES:  NIH RESEARCH POLICIES 
                             AND PRACTICES


                       WEDNESDAY, JUNE 14, 2006

                       HOUSE OF REPRESENTATIVES,
                  COMMITTEE ON ENERGY AND COMMERCE,
           SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS,
                                                          Washington, DC.


        The committee met, pursuant to notice, at 10:02 a.m., in Room 
2322 of the Rayburn House Office Building, Hon. Ed Whitfield 
(Chairman) presiding.
	Members present:  Representatives Stearns, Bass, Ferguson, 
Burgess, Blackburn, Barton (ex officio), Stupak, DeGette, Inslee, 
and Whitfield.
	Staff present:  Mark Paoletta, Chief Counsel for Oversight and 
Investigations; Alan Slobodin, Deputy Chief Counsel for Oversight 
and Investigations; Mike Abraham, Legislative Clerk, Ryan 
Ambrose, Legislative Clerk; John Ford, Minority Counsel; Jessica 
McNiece, Minority Research Assistant; and William Garner, 
Minority Professional Staff Member.
	MR. WHITFIELD.  I would like to call this hearing to order.
	Yesterday we had one panel of witnesses which was one 
witness, Dr. Susan Molchan, and today we are continuing this 
hearing on human tissue samples, NIH research policies and 
practices, and today we will have three panels of witnesses.
	First of all, I want to thank all of you for joining us this 
morning.  We made our opening statements yesterday so you are 
going to be very lucky.  You don't have to hear a lot of opening 
statements today.  And I would just make the comment that 
obviously all of us admire and respect the great work that is done 
at NIH.  It is a premier research institution that is doing a 
tremendous job in trying to find cures and preventions for all sorts 
of diseases and it is a premier institution.  I want to assure 
everyone today as the Chairman of this subcommittee, speaking for 
myself, I am not out to get anyone.  But we do think it is essential 
that this institution with its reputation take all steps necessary to 
ensure the integrity of its research, particularly when people are 
donating samples.  And we want to remove all possibilities of 
conflicts of interest or the appearance of conflict of interest.  And 
so that is why we are particularly excited that you are here today 
and we look forward to the testimony from all of you.
	On the first panel we have Dr. Thomas Insel, who is the 
Director of the National Institute of Mental Health at the National 
Institutes of Health, and we have Dr. David Friedman, who lives in 
Connecticut, so you will be the first two witnesses, and then in 
addition to Dr. Insel and Dr. Friedman, I guess accompanying you, 
Dr. Insel, we have Dr. Donald Rosenstein, who is the Acting 
Clinical Director at the National Institute of Mental Health.  We 
have Mr. William Fitzsimmons, who is Executive Officer of the 
National Institute of Mental Health, and then we have Ms. Suzanne 
Winfield, who is the Technology Transfer Officer at the National 
Institute of Mental Health, but it is my understanding that Dr. 
Insel, you will be testifying and these three people will be here to 
assist if it is necessary.  Is that correct?
	DR. INSEL.  That is correct.
	MR. WHITFIELD.  And Dr. Friedman, you will be testifying.  As 
you know, this is an Oversight and Investigations Subcommittee 
hearing and it is our policy to take testimony under oath, and Dr. 
Insel, do you or Dr. Friedman have any difficulty testifying under 
oath today?
	DR. INSEL.  I do not.
	MR. WHITFIELD.  And under the rules of the House and the 
rules of the committee, you are entitled to legal counsel to advise 
you, and I would ask, do either of you have legal counsel with you 
today?
	DR. INSEL.  I do not.
	MR. WHITFIELD.  In just a minute I am going to swear you in, 
but before I do, I want to ask Mr. Stupak, the Ranking Member, if 
he would like to make any comments before we get started.
	MR. STUPAK.  No, Mr. Chairman.
	[Witnesses sworn]
	MR. WHITFIELD.  You are now under oath, and Dr. Insel, we 
will call upon you for your 5 minute opening statement.

STATEMENTS OF THOMAS R. INSEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL 
HEALTH, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN 
SERVICES; AND DAVID L. FRIEDMAN, PH.D. 

	DR. INSEL.  Thank you very much, Mr. Chairman.
	I have handed out some testimony which probably would go 
much more than 5 minutes.  In thinking about this, I know you 
have many questions to ask.  We have a lot that we would like to 
discuss with you, and I think rather than going through those five 
or six pages, if I can just provide you a very simple statement 
which I hope will be seen as in essence a statement of the 
principles that we are here for because I think one of the things that 
we need to keep our eyes on here is what we are about and why it 
is so important that we protect the NIH mission.
	As you mentioned, I am the Director of the National Institute 
of Mental Health, and this is an agency that has a large extramural 
component.  Ninety percent of what we do is at universities and 
clinics and hospitals all around the country.  We are here to focus 
on the intramural part, which is ten percent of our effort and it is 
the part that resides here in Bethesda, Maryland, and the part that 
we often think of as the jewel in the crown because it is a place for 
highly innovative, exciting science.
	But I am also here as a physician and a scientist and I think you 
need to understand that I am absolutely committed to the mission 
of the NIH, which is to make discoveries to improve human health.  
For us, the clinical research which is part of what we do has to be 
understood as a real partnership and it can only be done because it 
is a partnership between clinical researchers who work as scientists 
and physicians and volunteers, research volunteers.  These are 
people who may have illnesses, they may be actually healthy 
subjects, but they undergo painful and sometimes risky procedures 
to participate in this important mission that we have at the NIH.
	We can only do this kind of work, it is just clear to all of us, if 
we understand that we are committed and the public understands 
that we are committed to minimizing risk, to protecting privacy 
and to using this information for the common good.  That just has 
to be a fundamental, and as we think about this, I think you will 
agree that this whole enterprise that we are involved with really 
rests on trust.  We can't do this without the public trust.  We can't 
do this without your trust and we can't do this without trusting 
each other to some extent, trusting each other that we will do the 
right thing.
	Whenever there is a conflict of interest or even a perceived 
conflict of interest, this trust is placed in peril and that is the 
situation that we are in this morning and as we talk about this 
individual case.  There are many policies and there are various 
levels of review to preclude conflicts of interest and we will go 
through those I think over the course of the next few minutes, but 
basically it comes down to one simple principle, and this has to be 
seen for us as true north.  That simple principle is that volunteers, 
their families, and the public must know that an NIH scientist is 
working for them and not for anyone else.  We cannot allow a 
scientist or anyone else at NIH to trade his or her public role for 
private gain.  It is very simple.  That is the basis from which our 
ethics policy is built.  Dr. Zerhouni sent out another message late 
last night to remind all NIH employees that that is a fundamental 
and that has to be understood.  Violating this simple principle 
jeopardizes public trust and everything we stand for at NIH and I 
will do everything, everything I can to ensure that this does not 
happen. 
	I look forward to your questions.
	[The prepared statement of Thomas R. Insel, M.D. follows:]

PREPARED STATEMENT OF THOMAS R. INSEL, M.D., DIRECTOR, 
NATIONAL INSTITUTE OF MENTAL HEALTH, NATIONAL INSTITUTES 
OF HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

        Mr. Chairman and distinguished members of the 
Subcommittee: I am Dr. Thomas Insel, the Director of the National 
Institute of Mental Health (NIMH), the component of the National 
Institutes of Health (NIH), an agency of the Department of Health 
and Human Services (HHS), tasked with responsibility for 
developing improved methods of diagnosing, treating, and 
preventing mental disorders, including schizophrenia, autism, and 
mood and anxiety disorders.    
        To accomplish this mission, the President and the Congress 
have provided the NIMH a staff of over 700 employees and a 
budget of approximately $1.4 billion for Fiscal Year 2006.  Nearly 
90% of this budget, or almost $1.2 billion, is allocated to the 
support of biomedical research and research training activities 
through various grant, contract, and fellowship mechanisms at 
universities, hospitals, and clinics around the nation.  The 
remaining $160 million per year is used to support a unique and 
critical intramural biomedical research program on the NIH 
campus in Bethesda, Maryland.  This program was established to 
provide rapid responses to public health emergencies and to 
support an environment of innovation and creativity for biomedical 
discoveries.  It is the operation of this intramural research program 
that is the focus of this hearing today.       
	First, I want to commend the Committee for its interest in NIH 
and the NIMH.  As a public servant, I am well aware of my 
responsibilities to be a careful and vigilant steward of the public 
resources entrusted to my care.   I know full well that you share my 
commitment on this point, and that you are working with all of us 
at the NIH to uphold the highest standards that can rightfully be 
expected by the public, whose support has enabled us to make 
remarkable strides in biomedical science. The Subcommittee has 
been working with NIH on several important issues and concerns 
that must be addressed, and I welcome the opportunity to 
cooperate with you as you continue to do so.  I have already met 
with Subcommittee staff on three occasions.  Based on the 
information that has been made available to me, I have taken 
action to improve our management of clinical samples.  I am 
already taking corrective actions.
        When I joined the NIMH in November 2002, I was impressed 
by the level of commitment to patients and families that was 
clearly so much a part of the culture of the Institute.  NIH has been 
called the "crown jewel" of HHS, and I believe it is such a jewel, 
among other reasons, because of the dedication and skill of those 
who conduct research in our intramural program.  It is because of 
them that we have made rapid progress against disabling diseases 
such as schizophrenia, bipolar illness, and depression.  Our 
stakeholders, especially the families who struggle with these 
diseases, need us to do all in our power to ensure that science 
advances as rapidly as possible. At the same time, science-no 
matter how laudatory its objectives and results-must be 
conducted with the utmost emphasis on ethical standards, ensuring 
public trust and support.  This is not negotiable.
        To assure that the science performed at NIMH is of the highest 
quality and meets stringent ethical standards, there are policies and 
procedures for the conduct of clinical research, including the 
management of clinical samples and interactions with industry.  
We realize that science and public policies change over time and 
that our rules and procedures must be continually scrutinized for 
relevance and effectiveness.  Although I am confident in the high 
ethical standards held by our staff, we occasionally find serious 
problems can occur, as is the case in most large organizations.  To 
the extent that problems result from systemic issues, I am working 
with the NIH leadership on institutional reforms.
        At NIMH we recognize that rapid progress requires 
collaboration, including the exchange of clinical samples, such as 
blood or cerebrospinal fluid.  As these samples are a non-
renewable resource from patients involved in clinical studies, the 
management of these samples is an important aspect of our 
stewardship of the public trust.  The following points may help the 
Committee understand our approach to this stewardship:

         Federal regulations require both Institutional Review Board 
(IRB) approval and informed consent, unless waived by the 
IRB, before a proposed study involving human subjects can 
begin.
         Samples derived from clinical studies conducted at the NIH 
are Government property under the responsibility and 
accountability of chief of the pertinent Laboratory or 
Branch.  The use of these samples is part of our obligation 
to research volunteers, who are our partners in the 
discovery process. 
	  When a trainee or non-tenured investigator leaves the 
NIMH, the disposition of the clinical samples collected by 
that junior investigator remains the responsibility of the 
Laboratory/Branch chief.  When the Laboratory/Branch 
chief leaves, the disposition of the clinical samples becomes 
the responsibility of the Institute's Scientific Director, who 
is also the director of the NIMH Division of Intramural 
Research Programs.
	 Collaboration with non-government scientists in the private 
sector is encouraged as part of an intramural research 
scientist's official duty.   This means that work with 
industry is done on official time and without non-
government compensation.  In the past, consultations with 
industry were permissible, subject to prior approval, if no 
Federal resources were used, no conflict or subject matter 
overlap with official duties was identified, and no other 
ethics concerns were present.
	 Investigators with potential conflicts of interest are 
required to disclose these potential conflicts to the IRB as part of the 
review process.  Like all executive branch employees, 
investigators who conduct clinical research generally may 
not participate in official matters in which they have a 
financial interest.
	 The exchange of clinical samples may be an important 
aspect of collaboration.  NIH is enhancing policies 
pertaining to the handling of human tissue samples and 
related intellectual property.  At NIMH, I believe we have 
not done enough to ensure that all clinical samples leaving 
from or arriving at the Institute were adequately monitored.  
And, while the NIH has a variety of possible written 
mechanisms (including the Cooperative Research and 
Development Agreement (CRADA), the Material Transfer 
Agreement (MTA), and the Simple Letter 
Agreement(SLA)), these mechanisms have not been used 
uniformly within the NIMH.
	 Current policies require that surplus tissue samples from 
completed studies need to be monitored through continuing 
IRB review if the samples are linked to patient identifiers.  
Although all of our intramural scientists engaged in clinical 
research are required to complete training in human 
subjects protections, I am concerned that NIMH 
investigators may not be uniformly aware of when the use 
of stored samples requires IRB review. 

        To address these concerns, I have done the following:
	 On May 2, 2006, I called an intramural faculty meeting to 
review current policies and expectations for the handling of 
clinical samples.
	 On May 26, 2006, the NIMH's Acting Clinical Director, 
Dr. Donald Rosenstein, and I sent a follow-up memo to all 
intramural scientists to remind them of the current policies 
and expectations.  Specifically, we are requiring that all 
collaborations involving clinical samples be documented 
with a written agreement (e.g., CRADA, MTA, or SLA) 
and that these agreements be cross-referenced for potential 
conflicts of interest.
	 Some of the clinical samples stored at the NIH are from 
studies that have been completed, meaning that they are no 
longer enrolling subjects and analyzing data.  We are in the 
process of reviewing all collaborations using stored 
samples from both active and inactive studies by intramural 
clinical scientists to ensure that they have appropriate 
approval and documentation.  For stored clinical samples of 
a completed study, we are requiring all investigators to 
have an active IRB-approved protocol with continuing 
review to permit monitoring of these samples. 

	It is important for the Subcommittee to realize that although 
standards and policies for clinical research and collaborations with 
the private sector have changed over time, certain rules of conduct 
have remained constant.   NIH scientists have always been 
required to abide by the general principles of government service.  
It is a public trust requiring employees to place the public health 
over private gain.   We need to be sure we provide NIH staff with 
the tools they need to maintain this high standard.
	Mr. Chairman and members of the Subcommittee, thank you 
for taking the time to look into these issues at the NIH and the 
NIMH.  We are very proud of the accomplishments that have been 
made by the NIH, and the fundamental and profound role the 
agency and its scientists have played in alleviating suffering from 
disease.  We are in a unique position because not only do we have 
to answer to our primary stakeholders-our patients and their 
families-but we have to answer to you and to every member of 
the public who has entrusted us with their hard-earned dollars to 
carry out NIMH's profound yet straightforward mission:  to reduce 
the enormous burden of mental illness and behavioral disorders 
through research on mind, brain, and behavior.   
I will be pleased to answer any of your questions.

	MR. WHITFIELD.  Thank you, Dr. Insel.  At this time we will 
recognize Dr. Friedman for his 5 minute opening statement. 
DR. FRIEDMAN.  Mr. Chairman, members of the committee, 
thank you for the opportunity to come before you today to discuss 
the facts relating to the use of cerebrospinal fluid and plasma 
samples in collaboration between Dr. Sunderland at the NIMH and 
Pfizer, Inc.
	I have great respect for the work of this subcommittee and the 
process of scrutiny underlying this hearing as I believe they will 
serve to clarify issues and resolve questions about the process and 
the intent of these key studies.
	I am appearing before you for several reasons.  First, I have 
firsthand information regarding some of the scientific issues 
relating to the interaction between Pfizer and Dr. Sunderland.  As 
an employee of Pfizer from 1995 to 2001, I initiated discussions 
between Dr. Sunderland and Pfizer regarding a possible scientific 
collaboration to search for and evaluate possible biomarkers of 
Alzheimer's disease.  Second, I have great respect for Dr. 
Sunderland as a scientist and clinician for his contributions to this 
important basic research.  I also have great respect for each of the 
key contributors of these experiments including my former Pfizer 
colleagues and the NIMH staff and associates of Dr. Sunderland 
who participated in the effort.
	I also recognize and respect the important contribution of the 
individual Alzheimer's patients and their respective families who 
contributed important CSF and plasma samples and underwent 
extensive testing over the past few decades resulting in the data 
and samples that are the subject of the discussion today.
	Finally, I appear today in part because not doing so might be 
misinterpreted as not supporting the nature, process, and intent of 
this research effort.
	I would like to make a few brief comments on the intent of this 
study as it relates to the issue of biomarkers.  The information we 
sought in this experiment was essential to enable several medically 
important aspects of Alzheimer's disease treatment, a goal with 
enormous significance to patients, their families, and society as a 
whole.  We sought to uncover new tools to enable the diagnosis 
and early detection of Alzheimer's disease.  These tools are viewed 
as essential in the development of new therapeutics due to the 
current limitations in the unequivocal diagnosis of Alzheimer's 
disease.  We also sought biomarkers for disease progression rate as 
well as biomarkers to stratify patients by specific disease stages.  
Last, we sought to identify markers of apparent normal individuals 
exhibiting no measurable cognitive defect who were at risk of 
developing Alzheimer's disease as a result of family history and/or 
genetic predisposition to the disease. This in turn might enable the 
treatment of cognitively normal yet affected individuals prior to 
their slow, progressive, debilitating decline.
	It is important to recognize that these classes of markers serve 
several important roles.  First, they facilitate and enable the proper 
clinical testing of potential Alzheimer's therapeutics under 
currently approved FDA guidelines.  Second, they may enable and 
inform regarding the proper clinical diagnosis of patients by the 
general medical community and may facility the appropriate 
determination of medication for an individual's specific stage of 
disease. Finally, when these medications become available, these 
markers can also serve to enable physicians to individually monitor 
the response of their patients to ensure optimal and cost-effective 
treatment.
	Given the magnitude of the societal burden of Alzheimer's 
disease now and in the near future, these are important tools to be 
uncovered and developed.  Dr. Sunderland recognized the 
significance of biomarkers and actively sought to identify 
biochemical markers as well as other types of markers in order to 
treat patients more effectively consistent with his role as an 
academic clinician at the NIMH.  This was clearly obvious from 
his academic publications which in turn was the vehicle through 
which I as a Pfizer employee initially contacted him regarding an 
effort to uncover these important tools to assist in the diagnosis 
and treatment of Alzheimer's patients.
	Thank you for the opportunity to testify, and I would be happy 
to answer any questions regarding these issues. 
	[The prepared statement of David L. Friedman, Ph.D. follows:]

THE PREPARED STATEMENT OF DAVID L. FRIEDMAN, PH.D.

        Mr. Chairman and Members of the Subcommittee, thank you 
for the opportunity to come before you today to discuss the facts 
relating to the use of cerebrospinal fluid (CSF) and plasma samples 
in a collaboration between Dr. Sunderland, at the NIMH, and 
Pfizer Inc. I have great respect for the work of this Subcommittee 
and the process of scrutiny underlying this hearing, as I believe 
that it will serve to clarify issues and resolve questions about the 
process and intent of these key studies. 
        I am appearing before you for several reasons. First, I have 
first-hand information regarding some scientific issues relating to 
the interaction between Pfizer and Dr. Sunderland. As an employee 
of Pfizer, from 1995 to 2001, I initiated discussions between Dr. 
Sunderland and Pfizer regarding a possible scientific collaboration 
to search for and evaluate possible biomarkers of Alzheimer's 
disease. 
        Second, I have great respect for Dr. Sunderland as a scientist 
and clinician and for his contributions to this important basic 
research. I also have great respect for each of the key contributors 
to this experiment, including my former Pfizer colleagues, and the 
NIMH staff and associates of Dr. Sunderland who participated in 
this effort. I also recognize and respect the important contribution 
of the individual Alzheimer's patients and their respective families 
who contributed important CSF and plasma samples and 
underwent extensive testing over the past few decades, resulting in 
data and samples that are the subject of the discussion today. 
Finally, I appear here today in part because not doing so might 
be misinterpreted as not supporting the nature, process, and intent 
of this research effort. 
        I would like to make a few brief comments on the intent of the 
study as it relates to the issue of biomarkers. The information we 
sought in this experiment was essential to enable several medically 
important aspects of treatment of Alzheimer's disease, a goal with 
enormous significance to patients, their families and to society as a 
whole. Specifically: 
	 We sought to uncover new tools to enable the diagnosis 
and early detection of Alzheimer's disease. These tools 
are viewed as essential in the development of new 
therapeutics due to the current limitations in the 
unequivocal diagnosis of Alzheimer's disease. 
	 We also sought to identify biomarkers for disease 
progression rate, essential to conduct cost-effective and 
efficient clinical drug trials given the heterogeneity of 
progression rates within this patient population. 
	 We also sought biomarkers to stratify patients by specific 
disease stages, knowing that various disease stages were 
likely to manifest differing components of the disease 
process and thus the potential to respond to different 
classes of therapeutics. 
	 Last, we sought to identify markers of apparently normal 
individuals, exhibiting no measurable cognitive defect, 
who were at risk of developing Alzheimer's disease as a 
result of family history and/or genetic predisposition to 
the disease. This in turn might enable the treatment of 
cognitively normal yet affected individuals prior to their 
slow, progressive, and debilitating decline. 

It is important to recognize that these classes of markers serve 
several important roles. 
	 First, they may facilitate and enable the proper clinical 
testing of potential Alzheimer's therapeutics under 
currently approved FDA guidelines. 
	 Second, they may enable and inform regarding the proper 
clinical diagnosis of patients by the general medical 
community, and may facilitate the appropriate 
determination of medication for an individual's specific 
stage of the disease. 
	 Finally, when these medications become available, these 
markers can also serve to enable physicians to 
individually monitor the response of their patients to 
insure optimal and cost-effective treatment. 

        Given the magnitude of the societal burden of Alzheimer's 
disease now and in the near future, these are important tools to be 
uncovered and developed. Dr. Sunderland recognized the 
significance of biomarkers and actively sought to identify 
biochemical markers as well as other types of markers in order to 
treat patients more effectively, consistent with his role as an 
academic clinician at the NIMH. This was clearly obvious from his 
academic publications, which in turn was the vehicle through 
which I, as a Pfizer employee, initially contacted him regarding an 
effort to uncover these important tools to assist in the diagnosis 
and treatment of Alzheimer's patients. 
        Thank you for the opportunity to testify today. I would be 
happy to answer any questions you may have regarding this matter. 

	MR. WHITFIELD.  Thank you, Dr. Friedman.
	As you know, this subcommittee had a hearing in 2004 related 
to this overall issue and as a result of that, NIH and HHS both 
revisited and dramatically strengthened their ethics regulation, I 
believe in 2005.  The question I would like to start off with, Dr. 
Insel, for you is, the period we are talking about relating to the 
spinal fluid transfer to Pfizer and Dr. Sunderland is roughly 1995 
to 2001, in that general time frame, but at that time certainly the 
Institute encouraged collaboration with outside researchers.  I 
mean, you can't do your job without doing that.  So I am assuming 
that throughout the entire NIH, it was totally acceptable for 
scientists to have outside consulting agreements with private firms.  
Is that correct or is that not correct?
	DR. INSEL.  Just to clarify, Mr. Chairman, there was 
encouragement for collaboration with both academic and private 
scientists but what you have asked about in terms of consulting 
arrangements was seen as something different than collaboration, 
so consulting arrangements with anyone outside of the Federal 
government comes into a very different category.  It could be 
approved but it would require approval and review.
	MR. WHITFIELD.  But it was not unusual for scientists to have 
outside consulting agreements?
	DR. INSEL.  It was not by any means unusual, but I just want to 
make sure we are clear about what we are talking about here.  You 
could have both collaboration and you could have consulting 
agreements, but you couldn't have them with the same agent.
	MR. WHITFIELD.  With the same agent?
	DR. INSEL.  That is right.
	MR. WHITFIELD.  You mean with the same outside party or--is 
that what you are referring to?
	DR. INSEL.  That is correct.
	MR. WHITFIELD.  Okay.  Now, before I get to Dr. Sunderland, 
let me ask you, any outside agreement that you had as a consultant, 
there would have to be disclosure of that agreement, I am 
assuming?
	DR. INSEL.  There is a whole system that would include prior 
approval--it would include review, approval, and then disclosure 
would be the minimal.
	MR. WHITFIELD.  So that protocol was already in place that you 
had to have the review, the approval and so forth, correct?
	DR. INSEL.  That protocol has been in place but I think as you 
know, beginning in 2005 there was first a moratorium on any 
outside activities, and in August of 2005 a new set of guidelines 
that now completely restrict outside activities and they are not 
permitted with either a pharmaceutical company or with biotech.
	MR. WHITFIELD.  Okay.  Dr. Sunderland had executed a 
material transfer agreement with Pfizer in 1998.  He also had the 
consulting agreement with Pfizer in 1998.  At that time was that 
permissible under existing NIH policies?
	DR. INSEL.  It would not have been approved to have a 
consulting agreement and an outside activity with the same 
company at that time.
	MR. WHITFIELD.  Okay.  So that would be a violation of the 
rules and regulations of the NIH at that time?
	DR. INSEL.  I wasn't here in 1998 but what I have been told is 
that that would not have been approved.
	MR. WHITFIELD.  Was it permissible under NIH policies in 
1998 to provide human research samples from NIH labs to a drug 
company and have a consulting arrangement with that same drug 
company about those samples?
	DR. INSEL.  No, that is not--that again is the same issue.  It is 
mixing collaboration and consulting, and that is where we get into 
this overlap between the scientific official duty of one of our 
researchers and their having some outside income from the same 
source.
	MR. WHITFIELD.  Right.  Now, when we get into patent rights, 
could you briefly explain--with the caliber of the research that is 
going on and the new avenues that you are moving, it is not 
unusual to be involved in new patients.  Could you briefly explain 
the policy of NIH as it relates to patent rights and the involvement 
of a scientist on your staff with an outside firm regarding patent 
rights?
	DR. INSEL.  Yes, of course. Ms. Winfield may be able to fill 
you in more from the Office of Technology Transfer's perspective 
because she does this for a living, but the opportunity to take 
discoveries and have them licensed is something that the NIH 
understands, appreciates, and encourages, and sometimes that can 
be done through collaborative activity.  It is important for the 
subcommittee to realize that we are encouraging that kind of 
activity and we are encouraging it as official duty.  We want 
people to work with industry to make discoveries and we want 
them to do that on government time.  In the case where a discovery 
could be licensed, there is an opportunity to pursue that through the 
NIH.  We have a technology transfer office that has a very well-
developed set of guidelines about how that can be done.
	MR. WHITFIELD.  Well, I know that Dr. Sunderland, for 
example, assigned his patent rights and was listed on Pfizer's 
patent application as a co-inventor and I know he received no 
money for that, so was there anything wrong with that?
	DR. INSEL.  So--let me back up a moment.  What you are 
telling me is that he was on a patent application that he received no 
money for.  We have no record in the NIH of a patent application 
with Pfizer or anyone else from Dr. Sunderland.
	MR. WHITFIELD.  Okay.  So you have no record of that?
	DR. INSEL.  So is that a problem for us, for any investigator?  
Let us take it away from this case, but to discover that someone has 
an application for a patent either with a private collaborator or 
without that relates to their official duty as a Federal employee and 
our agency doesn't know about it?  Yes, that is a problem.
	MR. WHITFIELD.  Okay.  Why is that a problem?
	DR. INSEL.  So what you are talking about is trying to license 
for potential commercial gain a discovery or an invention made 
through your Federal employment, and the Federal government has 
a stake in that.  That is no different than if you as a Member of 
Congress decided to take something that was part of your official 
duty as a Congressional Representative and to create it as an 
invention and try to have it licensed on the side without telling 
anyone from Congress about that.
	MR. WHITFIELD.  Dr. Friedman, you were with Pfizer from 
1995 to 2001?
	DR. FRIEDMAN.  Yes.
	MR. WHITFIELD.  And what were your responsibilities there?
	DR. FRIEDMAN.  I was part of an emerging biomarker group.  
Because of my doctorate in neuroscience, I had the responsibility 
for looking for alternative strategies for developing Alzheimer's 
therapeutics.  I was also part of a committee to look for new 
technologies that were enabling in terms of identifying new 
biomarkers across a spectrum of disease areas.
	MR. WHITFIELD.  But the research was focused on 
Alzheimer's?
	DR. FRIEDMAN.  No, the research I was doing was focused on 
biomarkers for a number of neurological diseases including head 
trauma and depression.
	MR. WHITFIELD.  And when did you first have contact with Dr. 
Sunderland about obtaining the spinal fluid from NIH?
	DR. FRIEDMAN.  I first contacted Dr. Sunderland late in 1997, 
having spent a year on this committee looking for new 
technologies and realizing that it would be possible to do these 
experiments.  We then sought a partner who had the experience 
and knowledge and access to samples that would make this project 
possible, so it was in the fall of 1997.
	MR. WHITFIELD.  And you all entered into a material transfer 
agreement with him to obtain these samples?
	DR. FRIEDMAN.  Pfizer did in 1998, yes.
	MR. WHITFIELD.  And at that time was there a consulting 
agreement in effect between Pfizer and Dr. Sunderland?
	DR. FRIEDMAN.  I wasn't part of any of the contracts or 
negotiations regarding the contracts.  Having participated in these 
types of collaborations before, it was not unusual to have a 
consulting arrangement as part of a collaboration, but in no way 
was I part of those discussions.
	MR. WHITFIELD.  So from your personal knowledge, you were 
not aware of that?
	DR. FRIEDMAN.  Well, not only that, but it wasn't my role as a 
scientist.
	MR. WHITFIELD.  Right.  How would you describe the success 
of the research that you conducted or that Pfizer was involved in 
relating to its efforts with NIH on this Alzheimer's project?
	DR. FRIEDMAN.  It is kind of a complicated question because 
there are multiple facets to that project, and so if you want me to 
speak in general about those?
	MR. WHITFIELD.  The one with the unknown biomarkers.
	DR. FRIEDMAN.  Okay.  So that was the project we did in 
collaboration with an external partner, Oxford Glycoscience.  That 
project where we are looking for unknown markers has in its 
technical feasibly not been matched today.  It was a huge effort to 
look for low-abundance markers in cerebrospinal fluid.  It led to 
the identification of over 100 proteins that were likely stage-
specific in terms of their release into the cerebrospinal fluid.  The 
follow-up of that process is ongoing.  I happen to know by looking 
at the patent literature that those patents have been updated the past 
couple of years so it looks as though Pfizer is actively pursuing not 
only the identification but the validation of those markers which 
takes several years, so I would view it as being highly successful.
	MR. WHITFIELD.  Right.  I see my time has expired, so Mr. 
Stupak, I will recognize you for 10 minutes.
	MR. STUPAK.  Thank you, Mr. Chairman.  Dr. Friedman, you 
indicated that you are familiar with the MTAs and the CRADAs 
that they use?
	DR. FRIEDMAN.  No, I indicated I wasn't familiar with them.  I 
wasn't part of the process of--
	MR. STUPAK.  But I mean, outside of Dr. Sunderland, were you 
familiar with them?
	DR. FRIEDMAN.  No, I am actually familiar with doing 
collaborations with academic investigators as part of my role, not 
just at Pfizer but at other drug companies as well.  It is not an 
unusual process, to say the least.  What I indicated--
	MR. STUPAK.  Let me ask you this.  I am looking at Exhibit #15 
in the book there, and this is an e-mail and you are carbon-copied 
on it, and you talked about "pleased that this is working out well 
both on the scientists' side and on the tech transfer side.  We do 
not need to have an MTA signed prior to CMC on March 12, 
Julie."  And it sort of goes through this meeting, and according to 
our understanding, you were at this meeting on February 28 when 
you went to see Dr. Sunderland.  Do you remember the meeting of 
February 20, 1998, when you went to meet--
	DR. FRIEDMAN.  In general I do.
	MR. STUPAK.  Okay.  Do you remember seeing this e-mail?
	DR. FRIEDMAN.  I have seen the e-mail several times, once 
obviously back then but also subsequently during my prior visits to 
begin discussions about my role.
	MR. STUPAK.  Well, my concern is, in this e-mail it says, "In 
discussions regarding Pfizer's needs and Sunderland's needs, Trey 
indicated he was very happy with MTA arrangement plus 
consulting that Kathy Smith has been discussing.  Trey was also 
very interested in publication in a reasonable timeframe and that he 
wanted to make sure that authorship would be based on scientific 
and intellectual contributions.  We indicated agreement on both 
matters."  It seems to me that on February 20 from reading this e-
mail and the whole of it, not just the part I quoted, that there were 
discussions about payment and things that Pfizer would receive 
from Dr. Sunderland.  Is that correct?
	DR. FRIEDMAN.  Yes, it is correct.  I was--
	MR. STUPAK.  Didn't you think that was unusual, that you 
would be paying a scientist at NIH--or NIMH--excuse me--for his 
samples and things like that?
	DR. FRIEDMAN.  First of all, this meeting was a mixture of both 
business and scientific people from Pfizer, so Kathy Monahan was 
part of the business end of the process.
	MR. STUPAK.  You were there and three other Pfizer scientists?
	DR. FRIEDMAN.  Yes.  Correct.  I was there because I had 
initially made contact with Dr. Sunderland and we had established 
a scientific relationship.  We had even begun the discussion about 
the collaboration prior to--
	MR. STUPAK.  Yeah, but it says "take care of Pfizer's needs and 
Sunderland's needs."
	DR. FRIEDMAN.  Those comments were actually from Kathy 
Smith regarding her interpretation of how the discussions about 
future--
	MR. STUPAK.  You didn't think that was what happened at that 
meeting?
	DR. FRIEDMAN.  No, I didn't say that at all.  I can't say clearly 
that at the time and even until recently, I don't know the difference 
between a CRADA and an MTA in terms of the implications.
	MR. STUPAK.  What did you understand Dr. Sunderland's need 
would be then?
	DR. FRIEDMAN.  I didn't try and interpret what his need would 
be.
	MR. STUPAK.  What were Pfizer's needs at the time of the 
February 20, 1998, meeting?
	DR. FRIEDMAN.  In a business sense, I don't know.  From a 
scientific sense, we were looking for someone who had well-
characterized samples.  We were looking for someone who was an 
expert in the field of Alzheimer's disease because without the 
combination of those, the efforts that we would put forth would be 
worthless.
	MR. STUPAK.  Did you think it was odd that you would be 
paying for these samples?
	DR. FRIEDMAN.  I didn't--in no way did I interpret that we were 
paying for the samples.  We were paying for the opportunity to 
have a collaboration with Dr. Sunderland and in no way did I know 
what the specifics of this type of--
	MR. STUPAK.  So you are saying all this money that Pfizer 
paid, it wasn't for the sample, it was for the opportunity to work 
with Dr. Sunderland?
	DR. FRIEDMAN.  That is my interpretation, yes.
	MR. STUPAK.  Really?
	DR. FRIEDMAN.  Exactly.
	MR. STUPAK.  Were samples just thrown in then as good faith 
or something?
	DR. FRIEDMAN.  I don't think you can put a value on the 
samples.  In spite of the discussion yesterday, I think any attempt 
to try and do that type of analysis is impossible.
	MR. STUPAK.  The most important thing was really the 
samples, weren't they?
	DR. FRIEDMAN.  No, the samples are actually useless without 
the clinical information associated with them.  They were--
	MR. STUPAK.  Couldn't you ake the samples and have them 
analyzed and have other labs take a look at it depending on what 
you are trying to do with those samples?
	DR. FRIEDMAN.  Alzheimer's--
	MR. STUPAK.  There was a great benefit to Pfizer, wasn't there?
	DR. FRIEDMAN.  Alzheimer's is a very complex disease.  
Knowing what type of patients these came from is almost as 
valuable as knowing--
	MR. STUPAK.  Well, not just the patients but also the patient's 
extended family, blood relatives, some who had--
	DR. FRIEDMAN.  Absolutely.  All of that data is critical to 
interpret the biochemical measures that we were acquiring as part 
of this collaboration.  We would never have ventured into this 
without having that complete set of information because otherwise 
it would be uninterpretable. 
	MR. STUPAK.  Do you know if Pfizer had other MTAs or 
CRADAs with NIH?
	DR. FRIEDMAN.  With NIH?
	MR. STUPAK.  Yes.
	DR. FRIEDMAN.  I wasn't aware, but I wouldn't be surprised if 
they did.
	MR. STUPAK.  But the samples and the clinical data were 
transferred under the MTA.  In fact, Pfizer was upset because they 
were transferred in June and they didn't get the data until August, 
right?
	DR. FRIEDMAN.  I wouldn't characterize it as Pfizer being 
upset.  There were probably members of this project who were 
more concerned with timelines that were upset about the timing of 
it but the scientists as part of the project recognized that we would 
need 6 months at least to acquire that type of biochemical data 
prior to integrating it with the clinical data to interpret it.
	MR. STUPAK.  You said you are the one who sort of initiated 
the conversation with Dr. Sunderland and Pfizer, correct?
	DR. FRIEDMAN.  Yes.
	MR. STUPAK.  Before you introduced Dr. Sunderland to other 
Pfizer officials, did you have conversations with him about what 
his role would be in this research?
	DR. FRIEDMAN.  Yes.  Can I clarify what that conversation 
was?
	MR. STUPAK.  At any time did money come up during that time 
as--
	DR. FRIEDMAN.  No, never.
	MR. STUPAK.  --payment for samples or for data?
	DR. FRIEDMAN.  It was a discussion of a scientific collaboration 
only.
	MR. STUPAK.  And do you know how money came up in this 
whole opportunity or this--
	DR. FRIEDMAN.  I wasn't part of those discussions.
	MR. STUPAK.  Who at Pfizer would be?
	DR. FRIEDMAN.  Kathy Smith would probably be one person.  
Barry Hess would be another. 
	MR. STUPAK.  Dr. Insel, according to our information, Dr. 
Sunderland is still on the payroll at NIH?
	DR. INSEL.  That is correct.
	MR. STUPAK.  Is any action being taken?
	DR. INSEL.  His case, as you know, was reviewed by the Office 
of Management Assessment as part of conflict-of-interest 
concerns.  There was a recommendation made, and the case was 
referred to the Commissioned Corps of the Public Health Service.  
He is technically a Commissioned Corps employee.
	MR. STUPAK.  So the recommendation was made.  When was 
that--to the Corps?
	DR. INSEL.  I sent that forward I believe on November 21, 
2005.
	MR. STUPAK.  Two thousand five.  As far as you know, did 
anything happen on that recommendation?
	DR. INSEL.  I have called and sent notes subsequently and as far 
as I know, there is no decision made yet by the Commissioned 
Corps.
	MR. STUPAK.  What was your recommendation?
	DR. INSEL.  My recommendation, which I believe you have in 
your package, was, I sent forward the Office of Management 
Assessment review--essentially it was about a five-page set of 
findings--and I gave them a one-paragraph cover note saying that I 
was really disappointed, that I thought of Dr. Sunderland as one of 
the people who had made tremendous contributions to the agency, 
but that I had been informed by the Office of Management 
Assessment that civil service employees who had similar levels of 
violations would have been recommended for termination.
	MR. STUPAK.  So were you recommending his termination?
	DR. INSEL.  I can't actually do that, sir.  I don't have the 
authority.
	MR. STUPAK.  I am not asking if you terminated him.  I am 
asking if you made a recommendation that he should be 
terminated.
	DR. INSEL.  Well, I tried to explain exactly what I said, that I 
told them that given the severity and the concerns about these 
findings, that had he been in the civil service, he would have been 
likely terminated based on what I had been told by the Office of 
Management Assessment.  They will have to make their own 
determination about that at the Commissioned Corps.
	MR. STUPAK.  So you don't want to make a recommendation 
then?
	DR. INSEL.  In fact, I can't.  I can't do any more than refer the 
case--
	MR. STUPAK.  How about Dr. Molchan?   Would you be her 
supervisor?
	DR. INSEL.  I am not Dr. Molchan's supervisor.
	MR. STUPAK.  If she was to get tenure, would you be involved 
in the process of whether or not she would receive tenure at NIH?
	DR. INSEL.  She is currently in the National Institute of Aging, 
so I wouldn't have anything to do with that.  If she were to come 
back to the National Institute of Mental Health and she were a 
tenured investigator, I would be involved as in my current 
temporary role as the Acting Scientific Director for about another 
month.
	MR. STUPAK.  So accountability then would depend upon the 
institute?  The National Institute of Mental Health, that would have 
had the accountability?
	DR. INSEL.  Let me ask you to unpack that a little bit more in 
terms of accountability.  Accountability for what in this case?
	MR. STUPAK.  Well, in this case let us say Dr. Sunderland.  He 
is a Corps individual so you don't have any control over that, 
right?
	DR. INSEL.  Right.
	MR. STUPAK.  So who would have accountability over him?
	DR. INSEL.  Well, this is where it gets complicated.  So indeed 
he is an employee of the Commissioned Corps.  He is essentially 
detailed to the National Institutes of Health where he has been for 
some 24, 25 years.  His supervisor is the Scientific Director of the 
Institute and so--
	MR. STUPAK.  Of NIH?
	DR. INSEL.  Of NIMH in this case, so we are one of 27 
components of the NIH, and NIMH has--
	MR. STUPAK.  Well, let us put it like this.  We find it a little 
funny on this side of the dais that Dr. Sunderland seems to still be 
working and does not seem to have any problems but the person 
who came to the committee with her concerns cannot get tenure at 
NIH, so we have some real questions here on this side so I guess I 
am trying to figure out who is making these--
	DR. INSEL.  Let me tease these two things apart.  You say you 
find it a little funny that he is still there and there is--
	MR. STUPAK.  I find it suspicious.
	DR. INSEL.  I actually find it a real concern.  This has been 2 
years since you have given us some information.  We have done a 
very thorough review.  We made some recommendations.  We 
made a referral.  We are now 7 months down the road and this 
gentleman is still waiting to find out about his fate.  I would 
separate that from the question about tenure of another scientist.  
Now, the decision about tenure--
	MR. STUPAK.  Now, the witness yesterday said that her 
supervisors were discouraging her from talking to the committee or 
discouraging her from blowing the whistle, if you will, and then 
when we find she doesn't receive tenure, I guess that is--we find 
that suspicious.
	DR. INSEL.  So if I may, if I can back up.
	MR. STUPAK.  Sure.
	DR. INSEL.  She was an employee of the NIMH until I believe 
1996, 1997.  At that point in time she was not on what we call a 
tenure track.  That is, she was essentially in a training position but 
an extended one.  She did apply for a tenure-track position.  It is 
my understanding that was done in 1997 and that is a competitive 
process both internal and external.  The NIMH, before they would-
-or NIH, before they would give tenure to an intramural scientist, 
they are going to do a very though competitive process to make 
sure we have got the best and the brightest person.
	MR. STUPAK.  Sure.  We find it amazing or amusing that she 
has 50 co-authored reports with Dr. Sunderland and nothing 
happens to him but she doesn't get her tenure and she is still 
waiting, but all those reports for one seem to be beneficial.
	MR. WHITFIELD.  The gentleman's time has expired.
	MR. STUPAK.  Thank you.
	DR. INSEL.  I would be happy to respond to that if I may.
	MR. WHITFIELD.  Okay.
	DR. INSEL.  All I can say that in the tenure process, it may seem 
ironic to you, but in fact, having 50 papers with your supervisor is 
not a plus.  You are looking for someone who is an independent 
thinker, who has created their own area of research, who can come 
in and function independently with their own resources, which is 
what we define as tenure track or tenure.  She certainly was 
considered in that process.  He had nothing--he was not on that 
committee.  Obviously this is done by an independent group.  They 
did have a short list.  My understanding is that she didn't make the 
short list and that happens all too often.
	MR. WHITFIELD.  We will go ahead, and if we have time, we 
will come back with some more questions.  Dr. Burgess, you are 
recognized for 10 minutes.
	MR. BURGESS.  Thank you, Mr. Chairman.
	Yesterday during our questioning, the issue came up.  Dr. 
Molchan said that this concept of the lithium study was one that 
she brought to the lab.  It was not a project she was assigned after 
arriving there.  But then when the contract or whatever expired and 
she leaves the lab, is that unusual then for that particular arm of 
research just to stop and no one to pick it up and continue that?  
Would that be the standard operating procedure of the NIH in that 
type of situation?
	DR. INSEL.  So if I may answer, it is a very in some ways 
complicated question because it depends on the individual lab and 
the individual project, but if I can speak to this particular case, I 
think it is important for the subcommittee to recognize that that 
was a study that essentially stopped accruing patients early in 
1993.  She did submit annual progress notes to the Institutional 
Review Board and the one in 1995 says that she would like to keep 
the study open even though it has been capped.  She hasn't brought 
anybody else in 2 years because she thinks there may be an 
opportunity to do additional studies.  But in August 8 of 1996, she 
actually sends a note in the annual note to the board saying that she 
would like to now terminate the study.  She leaves the Institute, as 
I understand it, in 1997.  Now, remember, there has been no 
additional accrual of patients since 1993 and there have been some 
papers published in the meantime, but she goes off and leaves for 
another agency, which is not actually a discovery agency like the 
NIH, it is a regulatory agency, the FDA, and as she said yesterday, 
I think my understanding was that this was her project, that wasn't 
a project of her supervisor's, one that she brought forward, so I 
don't think in a case like that it would be surprising after the 
person who had initiated the project decided to terminate it, that no 
one else decides that they want to pick up on it.  That is my 
understanding of how this took place.
	MR. BURGESS.  If I understood the tone of questioning 
correctly yesterday from the committee, there seemed to be a sense 
that there should be some type of central database for sensitive or 
delicate tissue samples and that someone at NIH should oversee 
that.  Now, I tried to get a sense from Dr. Molchan as to how many 
blood, urine, tissue samples there might be housed in the various 
refrigerators and warehouses at the NIH just in the intramural part 
here in Bethesda, and I really no one would even hazard a guess at 
a number, but I would suspect those numbers of samples must be 
in the millions to tens of millions when you think of all of the test-
tube racks and all the refrigerators and all the freezers contained in 
all those buildings out there.  Mr. Chairman, I might point out, all 
those buildings are named for appropriators, not authorizers, as we 
reconsider the reauthorization of the NIH.
	But is there currently any type of central way that you keep 
track of this?  If someone were to go out there today and start a 
spinal fluid study on Alzheimer's patients, would those samples be 
logged in, coded, and someone keep track of that over time?
	DR. INSEL.  So the investigator, and by that we could be talking 
about a lab chief or a staff scientist who is involved, would have a 
tremendous investment in the samples they are collecting, and we 
would expect them as part of their stewardship to do a very careful 
documentation of what they have and where they have it and how 
they are managing it.  But the question you are asking, is there a 
central database, that is, of 54 scientists.  Do they at some point 
pool all of their data on all of their freezers and refrigerators and 
what they have at any given time?  The answer is no.
	MR. BURGESS.  And is it a reasonable expectation that this 
committee might have that that would ever be in place or is the 
problem just that the number of samples is just too large?
	DR. INSEL.  I think it is a really interesting question to consider, 
and I think part of what happens, and as the Chairman said, we are 
sort of looking at some of these policies through the prism of a 
single case.  We want to make sure that whatever solutions we 
come up with don't create problems of their own, and what you 
don't want is a bureaucracy that makes it impossible to move 
quickly and to make discoveries in an environment like the NIH.  
At the same time you want to make sure you can manage what you 
have.  As we often say, if you can't measure it, you can't manage 
it, so you have to know what is there and you have to be able to 
know what has been used and what still remains.
	Up until this point, we have left it to the scientists themselves 
to make those determinations and then we review the scientists 
based on their stewardship.  The question you are asking is, should 
we put something in place in the era where we have these large lab 
management software systems?  Do we need that?  Well, some of 
the institutes have been doing that and already they are putting 
those ideas out on the table and trying them out.  Some of them 
have already taken them out on the road a bit to see how they 
work.  Dr. Gottesman may tell you a little bit more about that.  It is 
not as simple as it sounds.  It is not necessarily the solution to all 
problems but I think at this point is one thing that we really want to 
look at very seriously, and we are in the process right now already 
in the last few weeks of pulling together inventory of everything 
we have got, making sure we know what has been used and what 
hasn't and trying to figure out what would be the impediments to 
actually coming up with the kind of central database that actually 
might also articulate with other kinds of clinical research data that 
we have.  So I think there is an opportunity here, and we actually 
owe it to the subcommittee--
	MR. BURGESS.  I don't want to interrupt you but my time is 
going to draw short.  There are a couple things--I do want to 
explore this line of questioning a little further.  Not commenting on 
the rightness or wrongness of what Dr. Sunderland did, would we 
even be having this discussion if those samples had been used and 
there had been a blockbuster breakthrough?  I mean, myself as a 
taxpayer and a consumer of medical research at the other end, I 
might see that as a good thing and a worthwhile thing.  Would we 
even be having this hearing if there had been a wonderful 
extrapolation of that data and we had seen the onset of Alzheimer's 
delayed by ten years per patient?
	DR. INSEL.  Well, I appreciate that question.  I do think that it is 
important to separate out scientific collaboration, which was an 
exciting and promising and I think very useful endeavor, from this 
question of conflict of interest.  I think before you came in, I said 
the true north here has to be the question of separating out public 
role, official duty, from private gain, and if that wasn't on the 
table, then we are here to congratulate Dr. Sunderland on having 
done I think a really excited scientific collaboration which as you 
heard from Dr. Friedman may actually bear some really important 
discoveries for families with Alzheimer's disease.  So the question 
of having actually worked with industry to come up with new 
biomarkers for Alzheimer's, I think everybody would cheer him on 
to do that.
	MR. BURGESS.  Would it have been a tragedy if that 
breakthrough could have occurred and it didn't occur because 
those samples sat in a freezer somewhere--
	DR. INSEL.  Absolutely.
	MR. BURGESS.  --for 15 years?
	DR. INSEL.  I think it would be a real mistake to decide based 
on our considerations of these issues that when you have residual 
samples from a study like this that has been closed that we just 
dispose of them because they may have true value and could be 
used for discoveries.  We have examples over and over again--
hepatitis B, hepatitis C, AIDS where it is stored samples that have 
really brought out fantastic discoveries for human health.  There is 
an opportunity to do that here and it still may happen.
	MR. BURGESS.  Let me ask you this, because it kept coming up 
yesterday.  Is the scientist, the principal investigator under any 
obligation to go back to the person that sample is collected from 
and to reissue or redirect permission to study--
	DR. INSEL.  Reconsent?
	MR. BURGESS.  Reconsent.  Yes, sir.  Thank you.
	DR. INSEL.  The obligation is not to reconsent but to be very 
clear is that if you have got samples that are stored for a study that 
has been terminated, we call those residual samples and you have 
got them in the freezer and you want to use them again for any 
purpose that involves research, it is not up to the scientist to decide 
whether that should go forward or not.  We have a very clear new 
policy in place that says as of just the last few days that we want 
people to go back to the Institutional Review Board to let them 
know what new use they would like to make of remaining samples 
because we don't want to leave that in the hands of the scientist.
	MR. BURGESS.  What would the policy have been when the 
original lithium study was closed in 1996 or 1997?
	DR. INSEL.  I think the policy there was just very general, and if 
someone--I could certainly understand how someone could say 
well, these samples were taken to study neurochemistry in the 
cerebrospinal fluid, we are studying neurochemistry in the 
cerebrospinal fluid for Alzheimer's disease and could decide they 
might be used at that point in time.  Remember, now, that would 
require additional review.
	MR. BURGESS.  But your new policy that is in place would not 
leave one person as being the final arbiter as to what to do with 
these potentially very valuable samples; there would be oversight 
by the Institutional Review Board.  Is that correct?
	DR. INSEL.  Precisely.
	MR. BURGESS.  Thank you, Mr. Chairman.
	MR. WHITFIELD.  Thank you, Dr. Burgess.  At this time I 
recognize Ms. DeGette for 10 minutes.
	MS. DEGETTE.  Thank you, Mr. Chairman.  Dr. Insel, Mr. 
Burgess raised some thoughts in my mind about exactly what the 
IRB process is for these residual tissue samples, and you told him 
that it would be a shame if the result of this issue was that these 
samples were just destroyed, and I agree with you, but I also think, 
and you might know, I have introduced legislation about patient 
protections and all this, and you said we didn't need a reconsent 
process.  Now, as I understand it, in this situation the original 
tissue donors did give a consent process and it went through IRB 
review, right?
	DR. INSEL.  That is correct.
	MS. DEGETTE.  But I am not suggesting a reconsent process, 
which I think would be impracticable, but I do think in the original 
consent process, you need to have some kind of informed consent 
for the donor that these tissue samples may be used later on for 
some kind of a different experiment or process, correct?
	DR. INSEL.  Absolutely.  You will hear later from Dr. 
Gottesman that we actually have a new policy that will come into 
place that has to do with having to define what is the disposition of 
either stored samples or samples following the termination of the 
protocol.
	MS. DEGETTE.  Right, and this has been a problem not just 
with the NIH but with other research institutions recently, correct?
	DR. INSEL.  That is right.
	MS. DEGETTE.  And then you said that you would--that for a 
subsequent study on these tissue samples that might be a different 
study, they would have to go back to the IRB, right?
	DR. INSEL.  So I should just clarify because I knew we were 
short on time.  There are two options.  In some cases--I should say 
three options.  In a case like this where you are studying 
Alzheimer's disease, I don't know this but it very well may be that, 
for instance, the subjects in this lithium protocol were all dead by 
the time that the scientists wanted to use the samples.
	MS. DEGETTE.  Right.
	DR. INSEL.  That puts them into a very different class.
	MS. DEGETTE.  I know, but for a subsequent study.  I am not 
talking about the consent anymore.  I am talking about going back 
to have the subsequent study approved by an IRB.  That is what 
you--
	DR. INSEL.  Right.  It would either need to go--well, it would 
go to the IRB to ask the question, does this require reconsenting, 
does this require review, should this even be done, and there may 
be--
	MS. DEGETTE.  Just for the threshold issues, would that be a 
full IRB process or would that be like a threshold IRB process?
	DR. INSEL.  Right. These were questions that we are now 
entertaining.  I might ask Dr. Rosenstein, who is really the expert 
on the IRB issue, to comment on this because this is exactly the 
discussion we have been having in the last few weeks.
	DR. ROSENSTEIN.  You are asking about IRB approval of new 
use of existing samples?
	MR. WHITFIELD.  Excuse me, Dr. Rosenstein.  You are going to 
be testifying, so if you just stand up and raise your right hand.
	[Witness sworn]
	MS. DEGETTE.  Right.  Dr. Insel said in his statement to Mr. 
Burgess that for a new study using these leftover tissue samples 
that there would have to be some IRB process.  I don't have a lot 
of time and I have other questions for him, so if you can answer 
very quickly, I would appreciate it.
	DR. ROSENSTEIN.  The Federal regulations require that research 
with human samples undergoing initial and ongoing review by an 
IRB.  The question has to do with what the ongoing review is for 
existing samples.  That is the policy that has been clarified.  Those 
regulations have been in place a long time but haven't always been 
followed as completely as they should be.
	MS. DEGETTE.  And in fact, it wasn't followed in this case, 
right?
	DR. ROSENSTEIN.  Correct.
	MS. DEGETTE.  Okay.  Dr. Insel, let me get back to a couple of 
other things.  Now, I think you testified earlier that you became the 
director of the National Institute of Mental Health in 2002, correct?
	DR. INSEL.  Yes.
	MS. DEGETTE.  And Dr. Sunderland at that time was a lab chief 
there, right?
	DR. INSEL.  Yes.
	MS. DEGETTE.  And so you were there in 2004 when we had 
our hearings in this subcommittee and we found out that there were 
what we thought then was around $500,000.  Now we now it is 
over $612,000 in unreported payments to Dr. Sunderland, correct?
	DR. INSEL.  I haven't seen all the numbers but I will accept 
those.
	MS. DEGETTE.  It was lots of money.  Can I assume that you 
know what the payments were for or did you ask him what they 
were for?
	DR. INSEL.  Well, I have spoken with him about this but I have 
to clarify that.  I had not seen the documentation of any consulting 
agreements until very, very recently, only in the last few days, so I 
couldn't tell you what those payments were for at that--
	MS. DEGETTE.  Why didn't you see the--I mean, if this has 
been going on for 2 years?
	DR. INSEL.  Right.  So, this came out originally in June of 2004 
that this subcommittee brought this issue to the NIH and of course 
all of us began to move into high gear to try to understand what 
was going on here with some of our scientists.  The NIH decided 
that there should be only one investigation NIH-wide and that 
investigation would be done by the Office of Management 
Assessment.  We were told specifically not to pursue any of these 
questions with our own scientists, go back to work, make 
discoveries, continue to have an impact on human health--
	MS. DEGETTE.  So you assumed that they were investigated?
	DR. INSEL.  Precisely.
	MS. DEGETTE.  And now why--
	DR. INSEL.  Well, not only did I assume, I was--this was 
something that we all agreed would be done by one body.
	MS. DEGETTE.  Right, based on what you were told.  I am not 
being critical.  And so when you read those consulting agreements 
that he had or whatever they were 2 days ago, that was in 
preparation for this hearing today?
	DR. INSEL.  Right.
	MS. DEGETTE.  Okay.  Now, you had testified earlier to Mr. 
Stupak's question that you went through the whole process of how 
someone like Dr. Sunderland gets removed and so on and you told 
Mr. Stupak that you have concerns that it has taken so long to 
figure out a disposition of his situation.  Would that be an accurate 
statement?
	DR. INSEL.  I have concerns.
	MS. DEGETTE.  What concerns are they?
	DR. INSEL.  Well, it just seems to me that in this case, it has 
taken 2 years before there is any penalty or any decision made 
about someone's career.  I think that is an awful long time.
	MS. DEGETTE.  Especially in light of these egregious examples 
here, right?
	DR. INSEL.  Even if we didn't have egregious examples, I really 
think that in the spirit of due process, we deserve and our scientists 
deserve resolution of some of these issues so that we can all move 
on.  We need to heal as--
	MS. DEGETTE.  Have you let your superiors know that, that 
they need to get some kind of a resolution of this case?
	DR. INSEL.  I have spoken to several people and--but you have 
to remember, this case is no longer in the National Institutes of 
Health.  It is now sitting elsewhere.
	MS. DEGETTE.  I understand.  Now, I want to ask you one more 
question.  You were talking earlier about these computer programs 
that we have and ways that we can get central registries of these 
tissue samples and so on, and you were talking about--it sounds 
like your institute and the other institutes are at the very early 
stages of talking about how we catalog and cross-reference this 
data.  Would that be accurate?
	DR. INSEL.  So we are at the early stages of talking about it in a 
systemic way.  Individual large labs already do a lot of bar coding, 
a lot of lab management systems.  This is being done.  And as you 
heard yesterday from Dr. Molchan, Dr. Sunderland has an 
extremely good data-tracking system.  That is not the problem 
here.  So there are individual labs who are doing this very, very 
well.  The question is, should we be doing it as an institution, as an 
agency.  Should we have all that rolled into one interoperable 
database.
	MS. DEGETTE.  Well, I have had many, many short and long 
conversations with Dr. Zerhouni, and as you know, with the NIH 
reauthorization, his concept is more centralization of funding and 
more cross-institute collaboration on research which I happen to 
agree with that vision, but it seems to me if we don't even have the 
basic mechanism in place for cataloging and cross-agency 
utilization of tissue samples, it would be very difficult to have that 
kind of collaboration without the risk of many situations like the 
Sunderland situation coming up.  Wouldn't you agree?
	DR. INSEL.  I agree with what you are saying but again I want 
to clarify.  I think you have to separate out issues of data tracking, 
which in some ways are software systems issues that we can do, 
anyone can do.  That is different than the issue of oversight and 
how you make sure that people are doing the right thing, and that 
still--
	MS. DEGETTE.  Right.  It doesn't sound like we have got either 
one in place though.
	DR. INSEL.  Well, what I am telling you is that we are looking 
at ways of getting the tracking in place but if we simply did that, 
we wouldn't fix the oversight issue.  The oversight issue is the one 
that really needs to be a focus right now.  How do we make sure 
that people are doing what they are supposed to do.  We come 
back--I think you weren't in the room yet but--to true north, the 
central principle, public office separated from private gain.
	MS. DEGETTE.  Right.  Well, I am with you there.  What more 
do you think we can do to make that oversight a reality because the 
last set of hearings we had, and I was there, I was on this 
subcommittee, it was 2 years ago and yet here we are again.
	DR. INSEL.  So Mr. Chairman, if I may, we have actually 
brought a little diagram to give you some ideas of how we think 
about doing this, and these have been handed out to you.
	MS. DEGETTE.  Mr. Chairman, I would ask unanimous consent 
that the copies be made a part of the record.
	MR. WHITFIELD.  Without objection.  The copies are being 
passed out now.
	[The information follows:]



	DR. INSEL.  I wouldn't want the subcommittee to think for a 
moment that we don't have anything in place for oversight.  We 
have a great number of ways in which this is done, and what this 
diagram which you will have copies of demonstrates is that there 
are actually four different forms of oversight for anybody who 
wants to begin analyzing a clinical sample.  There is the 
Institutional Review Board that looks at the issues of human 
subjects' protections.  There is a Board of Scientific Counselors 
that looks at scientific quality and whether these are studies that 
should be done anyway.  There is the Office of Technology 
Transfer that deals with questions around collaborations.  And then 
the deputy ethics counselor, which has a very important role for 
making sure that there is no conflict of interest.  Now, we had all 
of these in place in 2004 but what we didn't have then were the 
arrows.  I think if there is a vulnerability in the agency, it was that 
we weren't well integrated, in some ways in the way you are 
talking about, Ms. DeGette, around trying to have a single agency 
approach to many of these issues and what we are building in place 
now both with electronic systems and with human power as well is 
making sure that there is cross talk across all of these different 
elements of oversight so that whenever someone applies for an 
MTA, there would be an opportunity to know whether it is indeed 
an outside agency with the same agent and to make sure that this 
goes to the Institutional Review Board at the same time.
	MR. WHITFIELD.  The lady's time has expired.  At this time I 
recognize Mrs. Blackburn of Tennessee.
	MRS. BLACKBURN.  Thank you, Mr. Chairman.  I thank each of 
you, and I am going to stay right there on the same issue where 
Ms. DeGette was, so basically what we have got are three primary 
groups that are doing research.  We have the NIH, we have 
academia, and we have private industry, and what we are trying to 
figure out is how we have appropriate oversight and not impede 
science.  What I feel like I am hearing from you is well, we have 
turned a blind eye to what the interface would be between those 
groups and we have kind of swept those relationships under the 
rug, and let relationships occur, let payments occur and then until it 
became an awareness issue, we chose not to address it.  Because 
what I am hearing from you now is well, we didn't have a way to 
inventory samples but now we are looking at the fact that we need 
a comprehensive inventory.  We have a brand-new policy of going 
back to the review board and then in February 2005, Dr. Zerhouni 
established a policy on outside consulting.  So Dr. Insel, what I 
think I am hearing from you is, you didn't think you needed the 
oversight until it came to the attention that there was misbehavior 
and wrongdoing and I understand and appreciate your concern for 
saying that someone deserves the due process through the situation 
and consideration but our taxpayers hold us responsible for 
exercising the oversight in being certain that their tax dollars and 
the research dollars are being spent appropriately and properly.  So 
to go back, we have gone a long way around the horn with Ms. 
DeGette's question and my question, so, very quickly, how do we 
have proper oversight and not impede the scientific research?
	DR. INSEL.  Well, I like the way you put your question because 
that really is finding the sweet spot between making sure that we 
have the oversight we need but at the same time not putting in too 
many speed bumps that delay our ability to find a discovery for 
Alzheimer's disease or autism or another very serious illness, and 
that is a delicate balance in some cases.  Some of the things that--
	MRS. BLACKBURN.  The action item.  You know, let us not talk 
it to death.  What do you see as the bullet points, the action items?
	DR. INSEL.  So for us the action items are new policies, and let 
me just go through what we have done even in the last few weeks.  
You know about Dr. Zerhouni's change last year.  We put a 
moratorium on the use of stored samples until we can develop a 
policy that makes sure that every stored--
	MRS. BLACKBURN.  Are you slowing down any research by 
putting that moratorium into play?
	DR. INSEL.  We very well may be.  We don't know that yet.  
We won't know that until we have a full listing of what is there.
	MRS. BLACKBURN.  Okay.
	DR. INSEL.  We are requiring that all collaborations be 
documented with a written agreement so that we have an 
opportunity to find out what is being done, where it is being done, 
and who is responsible, and those things can be reviewed both by, 
as I showed you with this diagram, by four different groups.  And 
in addition to that, we are making sure that the people within the 
intramural program, the scientists are fully educated about what it 
is these new expectations entail.  We have had two faculty 
meetings in the last month to go over these issues.  Dr. Gottesman 
will talk more about some of the things that are being done NIH-
wide.
	MRS. BLACKBURN.  So these are all your band-aids?  You 
basically have four band-aids that you are putting in place until 
you establish a policy?
	DR. INSEL.  Well, we have a policy but it is not necessarily a 
true fix.
	MRS. BLACKBURN.  And for how many years has the NIH 
being doing research?
	DR. INSEL.  Clinical research for close to 60 years.
	MRS. BLACKBURN.  For 60 years, so basically you have flown 
60 years without a policy?
	DR. INSEL.  We have a number of policies, but you have to 
recognize that science changes, the needs change--
	MRS. BLACKBURN.  I recognize that, and I appreciate that, and 
I have great respect for the work that you do and I want to see that 
work continue.  In that vein, how many employees does the NIH 
have in total?
	DR. INSEL.  I think the full number is about 17,000 to 18,000 
for all of NIH.
	MRS. BLACKBURN.  Seventeen to 18,000, and how many of 
those are researchers?
	DR. INSEL.  It depends on how you define a researcher.  I can 
tell you--
	MRS. BLACKBURN.  How many are working in the area of 
research?
	DR. INSEL.  Well, I would assume that almost all of them are 
involved in some form or another with the mission of the agency, 
which is research.  I can tell you more from my own institute, 
NIMH, where we have 700 employees.  We have 55 or 54 tenured 
or tenure-track scientists and we have got another 60 who are staff 
scientist or staff clinician positions, and there are about another 
150 to 200 post-doctoral fellows and other kinds of trainees.
	MRS. BLACKBURN.  Okay.  And then your total budget is how 
much?
	DR. INSEL.  Our budget for the entire institute, NIMH, is 
roughly $1.4 billion, and about 10 percent of that goes to the 
intramural program, which is the subject of this hearing, which is 
about $159 million in the current fiscal year.
	MRS. BLACKBURN.  Okay.  Out of that total budget of $1.4 
billion for NIMH, what percent goes to research?
	DR. INSEL.  There is about 94 percent, I believe, that goes to 
research support and there is another six percent that is used--I 
think that would be right--for research management, which is 
providing the administrative infrastructure for the research 
enterprise.
	MRS. BLACKBURN.  All right.  Great.  Now, in your role as the 
director at NIH and NIMH, have you ever performed any outside 
consulting duties?
	DR. INSEL.  No.
	MRS. BLACKBURN.  You have not?  Have any of you at the 
table performed outside consulting duties in your roles?  You have 
never had outside consulting agreements?  Dr. Friedman, have 
you?  No?  Okay.  All right.  Going back to Dr. Molchan from 
yesterday, I found it so interesting that she could have put so much 
work and energy into a project and then it comes to a stop, so let us 
look at these researchers and the research projects that you do.  
You used the term "independent thinkers" in talking about your 
researchers.  How do you prioritize your projects?  Do you let the 
researchers choose what they want to work on?  Do you have an 
agency agenda?  Do you all sit down and say we need to work on 
this, that or the other?  So how do you mesh those or are they just 
flying interconnectedly and just recently brought together?
	DR. INSEL.  So again, we are focusing on our intramural 
program, this small group, this jewel in the crown that is here in 
Bethesda which is about 10 percent of what our institute is about.  
In that case, we have a relatively small group of senior scientists 
who we look to help generate the most exciting innovative science, 
high-impact science that they can, and they are reviewed every 4 
years, and that review is a very rigorous one in which we bring in a 
panel from outside the agency to look at three things:  how the 
research is going, is it going in the right directions, are they doing 
the most cutting-edge work, are they innovative; stewardship, how 
well is this person actually using the resources that have been 
given and mentorship, how well are they training the next 
generation.
	MRS. BLACKBURN.  And how long has that review process 
been in place?
	DR. INSEL.  Oh, it has been going on at least as long as I know 
about the agency, which is over 20 years.
	MRS. BLACKBURN.  Okay.  Great.  And then how often do 
these researchers choose a project and then choose to terminate a 
project?  Does that happen very often, and do you have a library of 
research that other researchers can go back to if they are working 
on some type of research and then they find that there are 
applications for something that was not intended and they think, 
well, this may work.  What is your library process?
	DR. INSEL.  To answer your first question about how often does 
someone hit a dry hole, it is often, and that is to be expected.  The 
intramural program is for high-risk, high-yield science.  High risk 
also means that it may often fail, and we actually don't see that as 
a problem.  In terms of having a library of negative results, that 
library is in publications.  That is generally the repository of 
information for our field and people look to publications both for 
discoveries and for discoveries that can't be replicated.
	MRS. BLACKBURN.  Very good.  All right.  I think that is about 
it, and I have only a couple seconds left so I yield it back.
	MR. WHITFIELD.  Thank you.  At this time I recognize Mr. 
Inslee.
	MR. INSLEE.  Thank you.  Dr. Insel, I was looking at this quite 
colorful chart and it sort of circles a little vial here in the middle 
and I guess that vial is probably where they put the answers and it 
only looks half full on this chart, and it sort of I think is a pretty 
symbolic representation.  It just seems to me there is some 
ambiguity in these processes that needs to be fixed.  That is an 
observation of somebody just new to this issue.  But I want to ask 
you specifically about the situation with Dr. Sunderland.  I read in 
the papers that Mr. Robert Muse, Dr. Sunderland's attorney, said 
his client "didn't receive a dime for providing anything to Pfizer.  
He received fees for consulting as for lectures.  These are known to 
NIH and they were permitted under NIH rules."  And I guess the 
question I have is, in the relevant time period, do you have reason 
to believe that NIH had information regarding the specific 
financial relationship regarding the collaboration and involving the 
use of human tissue samples that were originally with NIH?
	DR. INSEL.  If you could clarify when you say the relevant time 
period.
	MR. INSLEE.  Well, before 2 days ago.  How is that?
	DR. INSEL.  I believe some of this information came to the 
investigation that was done starting in 2004 by the Office of 
Management Assessment.
	MR. INSLEE.  So before an investigation started, did NIH have 
information about the specifics of the collaboration that involved 
apparently use of NIH tissue samples?
	DR. INSEL.  Absolutely.  We had an MTA, a materials transfer 
agreement, between Dr. Sunderland and Pfizer that documented 
that there was a collaboration to send over 250 cerebrospinal fluid 
samples for analysis of proteins potentially relevant to Alzheimer's 
disease.
	MR. INSLEE.  So NIH was aware that there was a financial 
remuneration going to be paid to Dr. Sunderland?
	DR. INSEL.  Absolutely not.  So again, let me clarify.  We have 
to separate here a scientific collaboration which we encourage and 
which we actually want to promote as long as it is done as one's 
official duty from an outside activity consulting arrangement with 
the same agency, which has never been permitted, and in this case 
was undisclosed.
	MR. INSLEE.  So I want to make sure I understand.  The 
financial remuneration was undisclosed but the transfer of the 
tissue samples was disclosed?
	DR. INSEL.  Exactly.  And bottom line, had he come to you or 
anyone else at NIH and said at that time my arrangement is that I 
will be receiving financial remuneration for collaborative services, 
I will be using NIH tissue samples, they will be removed from NIH 
physical custody, is that permissible under our rules, what would 
have happened?
	DR. INSEL.  There is a way to do this and it is something that is 
called a cooperative research and development agreement.  So 
someone could say--a scientist could say I would like to transfer 
blood samples to company X and I want company X to pay my 
laboratory to support a junior investigator.  That is actually 
perfectly permissible and it is also a way of dealing with 
intellectual property.  All of that has been worked out so there are 
ways to do this but that is not what we are talking about here.
	MR. INSLEE.  Well, in what way is it different?  I guess what I 
am saying is, had permission been sought by this particular 
investigator for this relationship, would it have been granted?
	DR. INSEL.  Not in the way that it has been described in the 
staff report.  That kind of outside activity, consulting, would not 
have been permitted for someone who had a collaborative 
arrangement with the same agency.  What I am telling is that if 
someone wants to collaborate, we try to encourage that.  If there is 
intellectual property at stake, there is actually a way to manage 
that.  That is called this cooperative research and development 
agreement.  That was not actually in the case in this particular 
example.
	MR. INSLEE.  This may clear to everyone listening to this but I 
want to make sure I understand it as well.  In what way would it 
have not been consistent with those rules?  That it was going to 
outside the NIH financial structure or was it going to the person 
who took possession?  In what way would it violate those rules?
	DR. INSEL.  Because what this does is, it violates the 
fundamental principle, which we keep coming back to.  It is that 
overlap between public office and private gain, and the way that 
we would manage that generally is with this CRADA mechanism 
and allow someone to actually pursue a collaboration and 
potentially also seek intellectual property protection or patents.  
The mechanism used here, the materials transfer agreement, 
doesn't actually permit that and it is not reviewed in the same way.  
There is a very extensive review process for a CRADA that 
ensures that there is no outside activity, that there is no private gain 
involved.  That was not the case. This particular case was not 
reviewed in that way.
	MR. INSLEE.  What is the sanction if there is a violation of any 
of the several policies that you have talked about?
	DR. INSEL.  What is the penalty?
	MR. INSLEE.  Yes.
	DR. INSEL.  It is really wide range and it depends on the 
severity of the penalty and it depends on whether--for instance, in a 
case, and I don't want to go into this particular case because this is 
already under investigation elsewhere--but one could imagine that 
the central question that would be asked is, had someone sought 
approval, would it have been granted, is there actually an inherent 
conflict of interest here, those kinds of issues, and so the sanction, 
the penalty would range from reprimand to suspension to 
termination, depending on how those particular factors line up.
	MR. INSLEE.  Thank you.
	MR. WHITFIELD.  At this time I will recognize the full 
committee Chairman, Mr. Barton.
	CHAIRMAN BARTON.  Thank you, Chairman Whitfield and Mr. 
Stupak, for continuing this hearing from yesterday.
	My first question, Dr. Insel, what are the inventory control 
practices now in place at NIH for human tissue sample collection, 
maintenance and tracking purposes?
	DR. INSEL.  As I said before you came in, Mr. Chairman, we 
have no central tracking of human tissue samples NIH-wide at this 
point.
	CHAIRMAN BARTON.  Is there an effort to initiate such a central 
tracking system?
	DR. INSEL.  There certainly is.  There has been a lot of 
discussion partly as the result of the work of this subcommittee to 
figure out how we can do this much better, and I can give you a 
quick rundown of some of the things that we are involved with if 
that would be helpful.
	CHAIRMAN BARTON.  Now, we are preparing an NIH 
reauthorization bill which I hope to have public within the next 
month if not sooner.  Is this something that should be a part of that 
bill?
	DR. INSEL.  I think we need to dig it into a bit.  When you think 
about how you want to specify--I guess it is a question, if you will, 
of granularity.  Do you want to have a tracking system that goes 
after every freezer, every shelf, every sample and every component 
of every sample?  I think there has got to be a point at which we 
think about what the details would mean, and as we said earlier in 
the hearing, finding this sweet spot between promoting discovery 
and rapid advances in science but not putting in too many speed 
bumps for the purpose of oversight.  We need it, but we need to 
find a way to do it so that we are still able to make the kind of 
progress we need.
	CHAIRMAN BARTON.  Well, the staff memo that is attached for 
this hearing says the current NIH system for human tissue sample 
collection and maintenance is fairly loose and ad hoc.  Is that an 
accurate assessment?
	DR. INSEL.  I think if you take the pejorative term, pejorative 
connotation of ad hoc out, I would say that it is ad hoc in the sense 
that it is delegated to individual scientists who have the greatest 
investment in their own samples.  They have collected them, their 
careers depend upon them, and I believe as you heard yesterday 
from Dr. Molchan, even in this case, which has generated so much 
interest in tissue tracking, you have a scientist who apparently had 
a pretty good handle on exactly where every sample was and how 
to find it and he was able to generate 13 years after the fact the 
samples in question so I am not sure that I would say that it is 
loose, but I would say that it has been delegated to individual 
scientists to make sure that they are doing the job the way--
	CHAIRMAN BARTON.  But you are in agreement that the current 
system can be improved upon?
	DR. INSEL.  I think the current system needs to be improved 
upon.  The question is how.  We want to make sure that our 
solution doesn't create new problems, and that is why I don't want 
to rush into this.
	CHAIRMAN BARTON.  All right.  Well, let us go on to the next 
subject.  We have one of your researchers, a Dr. Trey Sunderland.  
Is he still on staff at NIH?
	DR. INSEL.  He is.
	CHAIRMAN BARTON.  Is he on full capability or is he on leave 
with pay or what is his current status?
	DR. INSEL.  He comes to work.  He is getting, as far as I know, 
full salary and he stills serves as the chief of the geriatric 
psychiatry branch.
	CHAIRMAN BARTON.  Okay.  So he is still on active duty 
without any--
	DR. INSEL.  That is correct.
	CHAIRMAN BARTON.  Are you aware that the subcommittee has 
got documents in evidence that leads us to believe that he has been 
compensated--I don't know how to put this--in a fashion that 
doesn't appear to comport with the regulations in place at NIH?
	DR. INSEL.  I have seen the subcommittee documents that 
suggest that he received outside income for consulting with Pfizer.
	CHAIRMAN BARTON.  Well, we have some evidence that shows 
$285,000 in payments that appear to be inappropriate, another 
$200,000 in various expenses that appear to be inappropriate, and 
over $300,000 in lecture fees that may or may not be appropriate.  
Now, those numbers add up to three-quarters of a million dollars.  
What is the average salary of somebody in his position or similar 
position at NIH right now?
	DR. INSEL.  Well, for someone who is a lab chief, the salaries 
vary between--generally between $150,000 and $200,000.
	CHAIRMAN BARTON.  So three-quarters of a million dollars in 
compensation of a questionable nature should raise some 
eyebrows.  It would certainly raise eyebrows if a member of this 
committee--I think our average salary--it is $165,000.  If I had 
outside income of $750,000 that I didn't report on my financial 
disclosure statement and came from people who had pending 
legislation before this committee, I would have an ethics 
investigation by the Minority party and probably a contested 
primary and every newspaper in the country asking for my 
resignation from Congress.
	Now, I understand that Dr. Zerhouni has changed the ethics 
requirement at NIH and some of what happened with Dr. 
Sunderland predated that, so it could well be possible that some of 
the things that are now unacceptable under the regulations at NIH 
were acceptable.  I haven't seen a timeline so I am not going to say 
with certainty that all of this compensation that I just enumerated 
will turn out to be unacceptable, but I will say with certainty that it 
seems puzzling to me that he still is in his current position with no 
apparent reaction from the administration at NIH.
	DR. INSEL.  Well, Mr. Chairman, if I may, I think it is 
important to realize that there has been an extensive investigation.  
There has been a set of findings.  The case has been referred.  He is 
an employee of the Commissioned Corps.  The NIH itself doesn't 
have the authority to either hire or fire Dr. Sunderland.  This is 
done through the Commissioned Corps. 
	CHAIRMAN BARTON.  But do you have the authority to put him 
on leave with pay?  You do have the authority to transfer him.
	DR. INSEL.  In fact, my understanding is that his disposition of 
his--of where he works and what he does is at this point in the 
hands of the Commissioned Corps, and if I can add--
	CHAIRMAN BARTON.  What would happen if Dr. Sunderland 
went out and robbed a bank and then reported to work?  Would he 
report to work with full benefits?
	DR. INSEL.  Let me explain that.  Had he been a civil servant 
and that is the case for over 90 percent of the scientists at NIH, this 
would have been resolved months ago and we wouldn't be having 
this discussion at this point in time.  We made a recommendation 
November 21.  We made the referral at that point to the 
Commissioned Corps.  It is really out of our hands at this point 
unfortunately, and I also want to add that I think that fixing this is 
not enough.  I think you need--the subcommittee needs to 
understand that the NIH intramural program, it is not good enough 
to just be clean.  It has to be Camelot. It has to be the place where 
no one will have any question about conflicts of interest.  There 
has to be some place in the United States where the public knows 
that there is no taint, that there is no question, that there is no 
outside investment that is involved, that this is being done for the 
public good.  This is the place.  And for anything to come up that 
would in any way soil that reputation, we need to take care of it 
and we need to do more than fix it.  We need to actually become 
the model for how this research is done.
	CHAIRMAN BARTON.  On a bipartisan basis, subcommittee staff 
has been working on this for at least 6 months and maybe longer, 
and the report that I get is that Dr. Sunderland failed to provide 
information, failed to cooperate.  What little information that we 
have gotten, some of it appears to be misleading or intentionally 
inaccurate, and unless I am briefed by you or your staff later today, 
Dr. Zerhouni's staff, nobody is disputing, that I am aware of, that 
some of the payments that I just enumerated are not facts, that we 
misinterpreted, that there is a misunderstanding.
	DR. INSEL.  So in the--
	CHAIRMAN BARTON.  And so we have a person who has on the 
surface suffered no repercussion, none, and you talk about a 
Camelot.
	DR. INSEL.  You can see why I am frustrated.  I should add that 
in the past few days I understand that his case has been referred to 
the Inspector General and to the Department of Justice, that that is 
based not on what the original investigation focused on, which was 
the questions about whether there was overlap between official 
duty and outside activities, that is based on some of the new 
accusations that the subcommittee has brought to our attention.
	CHAIRMAN BARTON.  Well, my time is expired.  We want NIH 
to be the crown jewel.  I would much rather be here hosting a 
hearing where we highlight the breakthroughs on Alzheimer's 
research.  My mother has Alzheimer's.  I would love to be 
commending Dr. Sunderland and yourself and the other doctors for 
medical research breakthroughs that make life better and easier.  It 
is no fun to be holding this kind of a hearing.
	DR. INSEL.  Amen.
	CHAIRMAN BARTON.  But it is inexcusable that in spite of the 
public changes that have been made at NIH, there really does not 
appear to be a cultural change where the institution and the 
members of the institution condemn the kind of behavior that 
apparently Dr. Sunderland has exhibited.  It is really, really 
disappointing.  And with that, Mr. Chairman, I yield back
	MR. WHITFIELD.  Mr. Bass.
	MR. BASS.  Thank you, Mr. Chairman, and I am not going to 
use my whole time here and I follow on with what the Chairman 
has said.  This is a little bit reminiscent of the controversy that we 
had back at the 1990s at Los Alamos when I was on the 
Intelligence Committee.  It was an issue fundamentally of culture 
and the relationship that the scientific community had with the 
administrative community.  Obviously the issues there were 
entirely unrelated to what we are talking about here today.  I 
believe that you have addressed the issue of what Dr. Sunderland's 
status is.  Are you aware of the fact that he may not actually be--
there is a possibility that he may not be at his desk all the time, that 
he has another job somewhere else or he may have a laboratory 
that he goes to somewhere else?  Is that--are you aware of that or 
not?
	DR. INSEL.  I am not aware that he has any other employment.
	MR. BASS.  All told, you have here allegations at least that 
there is an impropriety involving outside activity and consulting 
with the same agent.  There are issues of activity that is not 
allowed.  There are disclosure issues.  There may be patent issues 
involved.  Do you have specific recommendations for NIH or 
NIMH with respect to what new policies should be enacted over 
and above what has been done now that would correct this problem 
and return this agency to what the Chairman or you referred to 
rather as the Camelot of research entities?
	DR. INSEL.  Well, I do have a number of ideas about that, and 
of course, Dr. Zerhouni has spoken to the subcommittee on several 
occasions to explain many of the things that are being done in the 
ethics arena starting with first the prohibition against outside 
activities with either drug companies or pharmaceutical companies, 
putting in a whole new set of safeguards to make sure that we 
review any outside activity request, and also having increased 
requirements for disclosure.  All of that was done over the last 18 
months.  Here we are talking about some slightly different issues 
which have to do not much or not only with ethical violations but 
with questions about how our tissue samples and how our clinical 
samples in general are managed and there I think is part of why I 
put together this chart for you.  I wanted you to see that we do have 
several independent programs that oversee how clinical samples 
are used.  I think the challenge for us going forward is providing 
the appropriate integration of those programs and also the 
appropriate oversight within each one to make sure that people are 
doing exactly what they have been approved to do.
	MR. BASS.  And it is possible that this collaboration and 
consulting may have actually been of significant benefit to the 
research effort.  Is that correct or not?  Is it possible?  I mean, did 
the work that Pfizer did save NIMH a significant amount of time 
and money or not?
	DR. INSEL.  I think that is in fact the case.  My understanding is 
that the collaboration was fundamentally to measure two proteins 
in spinal fluid.  The antibody for one of those proteins was a 
licensed agent that wasn't widely available.  It is quite expensive to 
have those tests done, and Pfizer, as I understand it, agreed to do 
those free of charge at a tremendous savings to the agency.
	MR. BASS.  Fair enough.  I don't have any further questions, 
Mr. Chairman.
	MR. WHITFIELD.  Mr. Stearns.
	MR. STEARNS.  Thank you, Mr. Chairman.  Dr. Insel, you have 
been at your present position since 2002?
	DR. INSEL.  November 2002.
	MR. STEARNS.  You had mentioned in your conversation with 
members that you can't manage unless you can measure it, and you 
went on to say that Dr. Sunderland had a great tracking system.  I 
think those were your words just 20 minutes ago.
	DR. INSEL.  That is right.
	MR. STEARNS.  In this graph, the committee, trying to identify 
the collected spinal fluids, found that what Dr. Sunderland 
provided in 2005 is yellow.  Molchan provided 97.  This is sort of 
bluish amber.  And this is the accounted for samples.  Did you 
know that all these samples are unaccounted for?
	DR. INSEL.  Can I ask what you mean by unaccounted for?
	MR. STEARNS.  Spinal fluid for lithium studies.  Do you want 
me to show you this graph?
	DR. INSEL.  I haven't actually seen the graph but the spinal--so 
if we are talking about the study done from 1991 to 1993, we had--
there were 25 subjects who were entered into the study.  There 
were 15 who had two lumbar punctures who could have been used 
for Dr. Molchan's--
	MR. STEARNS.  Well, the staff is saying this is unaccounted for 
if you go to that graph.  Were you aware that these are 
unaccounted-for samples that we have no measurement of?
	DR. INSEL.  I really--with all due respect, I think--
	MR. STEARNS.  Do you dispute what the staff's graph is?
	DR. INSEL.  What I would dispute is what is meant by 
unaccounted.  Dr. Sunderland has not, as far as I know, given away 
all of his spinal fluid to anyone.  There are five -70 freezers--
	MR. STEARNS.  Let me just finish here.  I've got a memo here--
June 20, 2005, to you--oh, this is your original message and 
"Gottesman's office has been collecting rules, regulations, and 
policies.  We need the following specific information on GPB 
protocol:  a list of samples that went to Pfizer and not a list of 
names but a list that shows number of samples and protocol so we 
can link consents to samples, copies of consents."  It indicated that, 
you were sort of aware of all these unaccounted-for samples.  In 
fact, you were asking for it in this memo.  Do you want me to 
show you this memo?
	DR. INSEL.  No, I know the memo that this my--
	MR. STEARNS.  This is in 2005.  Would that be fair--
	DR. INSEL.  To--
	MR. STEARNS.  You were asking for the unaccounted samples 
in 2005?
	DR. INSEL.  Did I use the word "unaccounted" in the memo?
	MR. STEARNS.  I am told by staff you were looking for the data 
that would help to answer where these unaccountable samples 
were, so that was over a year ago.
	DR. INSEL.  I--the memo that I sent, the e-mail I sent was that I 
wanted to find out what was sent to Pfizer and for the protocol--
	MR. STEARNS.  Well, Pfizer or someone else, not necessarily 
just Pfizer.
	DR. INSEL.  I am sorry, but in the memo, what I was asking 
specifically was the request about Pfizer.
	MR. STEARNS.  You said you wanted the number of samples 
and protocol.
	DR. INSEL.  I wanted the number of samples that would have 
been sent and the protocols that were involved in those shipments.
	MR. STEARNS.  Are you saying you weren't aware of that large 
number of unaccounted samples?
	DR. INSEL.  I am saying this to me is a very different topic.  
You are asking--so my understanding is that Dr. Sunderland had 
something like 16 protocols in which CSF was collected and many, 
many samples from across those protocols were sent to Pfizer.  I 
wanted to get a listing of what was sent and what were the 
protocols that covered it.
	MR. STEARNS.  Well--
	DR. INSEL.  This is a question about one particular protocol 
done many, many years earlier that had to do with lithium which I 
must say is one of the smallest--
	MR. STEARNS.  Are you saying the graph is wrong?  Yes or no.
	DR. INSEL.  I am--I would dispute the term "unaccounted for 
samples."
	MR. STEARNS.  Okay.
	DR. INSEL.  Because it makes it sound as if they are lost.  They 
are not lost.
	MR. STEARNS.  Well, do you know what happened to them?
	DR. INSEL.  I can tell you that--you know, I--
	MR. STEARNS.  Can you tell me today what happened to all 
these samples?
	DR. INSEL.  I can tell you that Dr. Sunderland has a large 
number of CSF samples that are still stored at the NIH or through 
one of our contractors.
	MR. STEARNS.  In other words, today you can go back and 
identify all these samples today if we went out to NIH this 
morning?
	DR. INSEL.  This is really the core of what we have been talking 
about for the last hour.  I specifically don't have an accounting for 
every sample.  I have an accounting for the protocols.  I have an 
accounting for the--
	MR. STEARNS.  But the people who work for you have that, is 
what you are saying?
	DR. INSEL.  Dr. Sunderland would have--I think could account 
for everything out there.
	MR. STEARNS.  But you said you can't manage unless you 
measure, but here it has been a year and you can't measure where 
these unaccounted samples are, so how can you manage it?
	DR. INSEL.  I am disputing your use of the word "unaccounted 
for."  What I am telling you is that there are samples that remain 
under Dr. Sunderland's supervision.  He is expected to be 
accountable for them.
	MR. STEARNS.  But he has not been accountable to you at this 
point?
	DR. INSEL.  I have not specifically asked the question of him, 
where are the five missing tubes of the many tens of thousands that 
you have from 1991.
	MR. STEARNS.  Let me go to the financial disclosure to the 
IRB.  In part of that review process, Dr. Sunderland filed an 
exhibit which is 24, and the question which he checked off "no" 
said, "Have any investigators developed an equity or consultant 
relationship with a non-NIH source related to this protocol which 
might be considered a conflict of interest?"  He checked off "no" 
and Dr. Rosenstein, your signature I guess is on here too.  Do you 
think in light of what has happened here that Dr. Sunderland 
should have checked off "no."  Is that in your mind satisfactory 
that he checked off "no" on this form?
	DR. ROSENSTEIN.  This is a question to me?
	MR. STEARNS.  Yes.
	DR. ROSENSTEIN.  I to this day don't know what the precise 
details of the relationship between Dr. Sunderland and Pfizer 
Pharmaceutical is so I can't answer that question definitively.  I 
can say that if an investigator has a consultative relationship that is 
related to the research, then that should be checked off "yes."
	MR. STEARNS.  Well, let us just go back.  Let us say you knew 
the facts today of his relationship with Pfizer and you had to put 
your signature down here.  Would you have questioned Dr. 
Sunderland knowing what you know today about his relationship 
with Pfizer?
	DR. ROSENSTEIN.  Yes, I would have.
	MR. STEARNS.  And what would you have said to him?
	DR. ROSENSTEIN.  I would have asked for a description of the 
nature of the collaboration and would have brought that back to the 
full IRB.
	MR. STEARNS.  Would you allow him to vote to check off "no" 
on this form based upon what you know today?
	DR. ROSENSTEIN.  As you have heard, the samples that were 
sent to Pfizer were drawn from several different protocols.
	MR. STEARNS.  No, no, I mean just yes or no, if you knew back 
then what you know today about his relationship with Pfizer, 
would you have accepted him checking off "no" on this form?
	DR. ROSENSTEIN.  I would have raised the question at the IRB 
meeting, to ask for an explanation.
	MR. STEARNS.  And you would say Dr. Sunderland, is it 
possible that yes, you do have a disclosure and you should attach 
or append to this document your disclosure as what the form is 
requesting?
	DR. ROSENSTEIN.  Yes.
	MR. STEARNS.  So you would have done that knowing what 
you know today?
	DR. ROSENSTEIN.  Yes.
	MR. STEARNS.  So Dr. Insel, who is this Commissioned Corps?  
You are pretty much saying you can't do anything with Dr. 
Sunderland.  You know that he is going to testify and you probably 
know he is probably going to take the Fifth.  That is probably 
almost a 99 percent conclusion.  I mean, I read his lawyer's 
comment here.  He wouldn't come here unless the committee 
voted and he wants all his rights which I respect and he should 
have his rights.  But I think it is pretty much a foregone conclusion 
he is going to take the Fifth, and with that in mind, you are saying 
you have no responsibility for his supervision or his employment 
or anything, that he has to report to this Commissioned Corps.  Is 
that what you are saying today?
	DR. INSEL.  No.  I am his supervisor because--
	MR. STEARNS.  Are you his supervisor?
	DR. INSEL.  As the Scientific Director, and I am in an acting 
capacity in that job for the next few weeks--
	MR. STEARNS.  Because you told Chairman Barton that you 
could not fire him, you could not do anything.
	DR. INSEL.  That is right.
	MR. STEARNS.  Now you are saying you are his supervisor?
	DR. INSEL.  And I have been--both things are true, so he is a 
member of the Commissioned Corps which means that he is 
essentially detailed to the NIH and hiring, firing, and promotion 
are done through the Corps, but the day-to-day supervision is done 
at the NIH.
	MR. STEARNS.  Like in a corporation, the hiring and firing is 
done through the personnel agency but the CEO can fire anybody 
he wants, and I assume that is what you are so--
	DR. INSEL.  Are you making a recommendation--
	MR. STEARNS.  The Commissioned Corps hires him but 
certainly if you felt his behavior was abhorrent, couldn't you make 
a recommendation that he be put on administrative leave?
	DR. INSEL.  I have done this.  I have--there was an investigation 
and there was a recommendation that--
	MR. STEARNS.  What was your recommendation?
	DR. INSEL.  The recommendation to the Commissioned Corps 
was that we--based on the findings from the Office of Management 
Assessment, I was deeply disappointed and it appears to be--I think 
I said the violations were severe enough to merit termination were 
he in the civil service.  I can't tell them what to do but I can tell 
them what we would do if he were--
	MR. STEARNS.  So you recommended to the Commissioned 
Corps that he be dismissed?
	DR. INSEL.  Yes.
	MR. STEARNS.  Okay.  Thank you, Mr. Chairman.
	MR. WHITFIELD.  Mr. Ferguson.
	MR. FERGUSON.  Thank you, Mr. Chairman, and I appreciate 
your having this hearing.
	I have some questions for Dr. Friedman actually.  So Dr. Insel, 
you can just catch your breath for a few minutes.  You have been 
getting a lot of questions this morning.  Dr. Friedman, I didn't 
want you to feel that you were wasting your time this morning 
sitting here.  But I want to further examine this relationship 
between Sunderland and Pfizer, and I read your testimony.  You 
seem to know a little bit about that.  So let us back up for a second.  
To your knowledge, did Pfizer contribute resources to the 
screening effort involved in these NIH samples?
	DR. FRIEDMAN.  They contributed a tremendous amount.  
There were at least half a dozen people that worked for years as 
well as enabling technology to be developed.
	MR. FERGUSON.  What kind of commercial products came from 
that?
	DR. FRIEDMAN.  No commercial products.
	MR. FERGUSON.  Zero?
	DR. FRIEDMAN.  To the best of my knowledge.
	MR. FERGUSON.  Could this type of research, this biomarker 
research that you have described, is it possible that this research 
would contribute to development of treatments for Alzheimer's?
	DR. FRIEDMAN.  It is viewed as being critical for development 
for treatments.
	MR. FERGUSON.  What happens to this kind of research?  It gets 
published, what happens when someone conducts significant 
research that could have a real impact on--
	DR. FRIEDMAN.  That is above and beyond what I know about 
this particular collaboration.
	MR. FERGUSON.  In general.
	DR. FRIEDMAN.  In general, there is a point where it gets 
published and that usually follows patent applications but it's 
always dependent on the distribution of the intellectual property 
which is usually decided in advance.  That is my basic 
understanding of it.
	MR. FERGUSON.  Who reads the publications?
	DR. FRIEDMAN.  Dr. Insel would be a good example of who 
reads the publications.  Everyone in the scientific community does.  
It is open for input and that is one of the cornerstones of basic 
science.
	MR. FERGUSON.  So anybody in the health community could 
benefit from this research of it is published and--
	DR. FRIEDMAN.  As a matter of fact, I think that they could 
even benefit from the patent application information as well.  
There is a tremendous amount of information that is in the public 
domain and has been for years.
	MR. FERGUSON.  Okay.  Now, we know that the rules for these 
consulting arrangements have changed since this particular 
instance that we are looking at today, that Dr. Zerhouni has told us 
about that, that the rules at NIH have changed regarding what is 
proper since this consultative relationship that Dr. Sunderland had 
with Pfizer, correct?
	DR. FRIEDMAN.  That is what I am hearing.
	MR. FERGUSON.  How would you characterize this relationship 
between Dr. Sunderland and Pfizer?
	DR. FRIEDMAN.  With regard to--
	MR. FERGUSON.  The activities, the consulting relationship that 
Dr. Sunderland had with Pfizer.
	DR. FRIEDMAN.  I really know very little--
	MR. FERGUSON.  You played a role in the initial--
	DR. FRIEDMAN.  What little I know about the consulting 
arrangement I have learned in the past few months being a part of 
this process.  I am really not in a position to comment.  I only 
know fragmentary information.  I mean, if you want me to 
comment on information that is part of the committee report, it 
would be a totally uniformed--
	MR. FERGUSON.  Yes.
	DR. FRIEDMAN.  I will make one comment.  From my 
experience of being part of several collaborations in different drug 
companies, direct compensation of $25,000 a year for the level of 
activity that Dr. Sunderland contributed to this project is modest at 
best.
	MR. FERGUSON.  How do these situations police themselves?  
Whose responsibility is it to police these--
	DR. FRIEDMAN.  To police them?
	MR. FERGUSON.  Yes.
	DR. FRIEDMAN.  From the point of view of a drug company?
	MR. FERGUSON.  Sure, or the point of view of any of us looking 
at these situations.
	DR. FRIEDMAN.  I wouldn't have any clue.
	MR. FERGUSON.  Well, would it be fair to say that a company 
in one of these situations is relying on the consultant to make a 
determination whether the relationship is appropriate or not?
	DR. FRIEDMAN.  It would be a guess if I answered that because 
I really have no knowledge of that.
	MR. FERGUSON.  What is your guess?
	DR. FRIEDMAN.  It is a fair assumption.
	MR. FERGUSON.  Okay.  That is all I have.  Thank you very 
much.  I yield back.
	MR. BURGESS.  Will the gentleman yield for just a moment?
	MR. FERGUSON.  I would yield to Dr. Burgess.
	MR. BURGESS.  Dr. Friedman, you testified that the markers 
were in fact critical, the research into the biological markers in 
Alzheimer's was a critical part of that research?
	DR. FRIEDMAN.  I commented that the identification of these 
markers is critical to the development of Alzheimer's therapeutics 
from the point of view of large drug companies.  That is part of, as 
you are well aware, the necessity of tracking any kind of 
efficacious response to a therapeutic over a reasonable period of 
time.
	MR. BURGESS.  And yesterday we heard testimony that the 
samples themselves were by virtue of having all of the genetic and 
clinical data on the people from whom they were recovered, that 
the samples themselves were extremely valuable.  I guess what is 
troubling me is, in 1995, 1996 and 1997, you closed the study on 
an aspect of Alzheimer's that is critical to understand on samples 
that were widely acknowledged to be very valuable, and as a 
taxpayer and perhaps one day a consumer of whatever might be 
developed from this research at NIH, I am more troubled by that 
than anything else I have heard this morning, that we have a 
valuable field of study that we are basically just capping and 
walking away from and leaving in the refrigerator.  I think--part of 
me says we should be grateful that someone picked this up and ran 
with it.
	MR. FERGUSON.  Are you looking for a response on that 
because I would like to reclaim my time?
	MR. BURGESS.  I was looking for a response from anyone who 
feels moved to respond to that.
	DR. FRIEDMAN.  I think Dr. Insel made the point which I will 
reiterate, good science never disappears.  It is picked back up again 
by other investigators either in the intramural programs or 
extramural programs.  People at drug companies--
	MR. BURGESS.  Since he is going to reclaim his time, you came 
perilously close to just disappearing back in the corner of that 
refrigerator when the study was capped in 1995 or 1996 before 
someone continued some type of research with those samples on 
biomarkers which we have admitted are critical to the 
understanding of Alzheimer's disease, on study samples that were 
very valuable because genetic contact and makeup of the study 
participants was known.  I am just troubled that that might have 
not happened.
	MR. FERGUSON.  Now I am really going to reclaim my time.  
Just in closing, Mr. Chairman, the point I guess I am trying to draw 
out and confirm is that there can be great value, it seems to me, 
there can be great value to these collaborative arrangements and 
that is what it sounds like some of you have said this morning as 
well.  There can be tremendous value to these collaborative 
arrangements but of course, the ends don't justify the means if they 
are not being done in a proper way, if they are not being disclosed 
in a proper way.  To this point it seems like the policing for these 
arrangements has largely fallen to the researcher, the investigator 
themselves.  That is probably why it is a good idea that Dr. 
Zerhouni is laying out some new guidelines.  But we have to--and 
we all want the Camelot that you had described before, but it is 
going to be very important for us as we move forward, all of us 
together, to make sure that we don't lose the value of these 
collaborative efforts because of the enormous importance of the 
work that NIH is doing for the health of the Nation, and we just 
have to make sure that we are doing it in the right way and we 
have to make sure that we don't have this ends-justify-the-means 
mentality.  I think maybe that is how I would sum up my feeling 
on this, and I would suspect that may be true for others on the 
panel as well.  Thank you, Mr. Chairman.
	MR. WHITFIELD.  Thank you.  Just one other question, then we 
will get the second panel.  Before I ask that question, did you have 
a unanimous-consent request, Ms. DeGette?
	MS. DEGETTE.  Yes, Mr. Chairman.  I am sorry I missed the 
opening statements yesterday and I would ask unanimous consent 
that I be allowed to submit mine for the record.  I would also ask 
unanimous consent that the record be kept open for this panel and 
the next panel and the panel yesterday for the requisite number of 
days for additional questions if members have--
	MR. WHITFIELD.  Without objection, so ordered.  Dr. 
Friedman, you had testified that when you initiated this discussion, 
the initial discussion with Dr. Sunderland, that you were primarily 
focused on the transfer of the material and so forth and you were 
certainly not focused on meeting any ethical requirements at NIH.  
Is that true?
	DR. FRIEDMAN.  Well, it certainly wasn't my responsibility.
	MR. WHITFIELD.  Right, not your responsibility.
	DR. FRIEDMAN.  But it also wasn't true that I was focused on 
the transfer of the samples.  I was focused on setting up, being 
participatory in setting up a collaboration.
	MR. WHITFIELD.  Collaboration.  Okay.  Now, I just want to 
read one excerpt to you.  On Exhibit 41, if you would turn to that, 
this is a letter from Mr. Robert Muse, who I assume is the attorney 
for Dr. Sunderland, and in that exhibit it is a letter from Dr. Muse 
to Holly Beckerman-Jaffe, who is the Director of the NIH ethics 
office, and the reason I want to bring your attention to page 9 is 
that in this letter, Mr. Muse refers to you, and he said at the time of 
his inquiry, and I am assuming as you are exploring this coloration 
opportunity, Dr. Friedman was not aware that Dr. Sunderland had 
any prior association with Pfizer and that Dr. Sunderland promptly 
notified Dr. Friedman of this and stated that he would not be able 
to undertake any actions with regard to the collaboration until such 
activity was cleared and approved by NIH.  Do you remember 
having that conversation with Mr. Muse?
	DR. FRIEDMAN.  I remember the conversation with Mr. Muse.  
I don't remember the exact details of that exchange but at no time 
was I involved in asking about what Dr. Sunderland's 
responsibilities were.  That was his responsibility.  Mine was to set 
up a collaboration and--
	MR. WHITFIELD.  But Dr. Sunderland did notify you that he 
would not be able to undertake any action with regard to the 
collaboration until such activity was cleared and approved by 
NIH?
	DR. FRIEDMAN.  What I recall is that Dr. Sunderland informed 
me that he needed to take care of these issues on his own before he 
could proceed.
	MR. WHITFIELD.  And then he went on to say in turn Dr. 
Friedman's goal was to make sure that the business, medical, and 
administrative people at NIH were fully informed.
	DR. FRIEDMAN.  That is certainly not true.  In no way did I 
have any business responsibilities nor would Pfizer have given me 
those in any way.
	MR. WHITFIELD.  Okay.  And as a matter of fact, Dr. Insel, I 
think you had previously stated that the policy even at that time 
was that if you were in collaboration with an outside entity and you 
had a consulting agreement with that entity, that that was not 
proper.  Is that correct?
	DR. INSEL.  That is correct.
	MR. WHITFIELD.  At this time I would like to thank you all 
very much for your testimony and for being here today.  I think 
this has been quite useful as NIH looks forward, moves forward to 
deal with these complicated issues and we want to thank you for 
the great work that you do at NIH and we look forward to 
continuing working with you as we make an effort to make sure it 
is a Camelot type of agency.  Thank you very much.  At this time I 
would like to call up the second panel, and on the second panel we 
have Dr. Trey Sunderland and Mrs. Karen Putnam, and if you all 
would please come forward and sit at the witness table, we would 
appreciate that.  Dr. Trey Sunderland is the Chief of the Geriatric 
psychiatric branch at the National Institute of Mental Health, and 
Karen Putnam worked for Dr. Sunderland and is a former 
employee of the National Institute of Mental Health.  They are here 
with us today pursuant to a subpoena.  On May 24, 2006, the 
subcommittee invited these two individuals to voluntarily testify at 
this hearing but they declined.  On June 3, 2006, Chairman Barton 
authorized subpoenas to be issued to compel their appearance, 
which were subsequently served.  My understanding is that these 
witnesses will rely on their Constitutional right not to testify at 
today's hearing.  I believe that this privilege which is the only 
basis upon which a witness may refuse to cooperate with an 
inquiry by the House should be personally exercised before the 
Members as we have done in the past.  That is why we have 
insisted on the appearance of Dr. Sunderland and Mrs. Putnam 
today.  Given the importance of their testimony to this 
subcommittee's fact-finding processes, I would hope that these 
individuals might reconsider their decision to invoke this Fifth 
Amendment right and cooperate with the subcommittee on this 
critically important investigation.  Dr. Sunderland and Mrs. 
Putnam, you are aware that this subcommittee is holding an 
investigative hearing and in doing so it is the practice of the 
subcommittee to take testimony under oath.  Do any of you have 
any objection to testifying under oath today?  Okay.  As you know, 
under the rules of the House and the rules of the committee, you 
are entitled to have legal counsel.  Do either of you have legal 
counsel with you today?
	MS. PUTNAM.  Yes, sir.
	MR. WHITFIELD.  And would you give the name of your legal 
counsel, please?
	MR. SHURGLER.  Your Honor, David Shurgler.
	MR. WHITFIELD.  David Shurgler.
	MR. SHURGLER.  I am licensed to practice in Washington, D.C.
	MR. WHITFIELD.  Thank you.
	DR. SUNDERLAND.  Robert Muse is my attorney.
	MR. WHITFIELD.  Robert Muse.  Okay.
	[Witnesses sworn]
	MR. WHITFIELD.  Thank you very much.  At this time both of 
you are under oath, and I would ask either one at this time, do you 
have any opening statement that you would like to make, Dr. 
Sunderland?
	DR. SUNDERLAND.  No, sir.
	MR. WHITFIELD.  Dr. Putnam?  Well, in that case, I would like 
to ask a question.  I would recognize myself.  Dr. Sunderland, 
according to records from Pfizer, the names and other privacy 
information of about 120 people, patients and volunteers who 
provided spinal fluid in National Institute of Mental Health studies, 
were inadvertently disclosed in 1999 shipments by your branch to 
Pfizer as part of one of the biomarker projects.  Now, Dr. 
Sunderland, did you know about this disclosure and why this 
occurred?
	DR. SUNDERLAND.  Chairman, as you know, you have had 
correspondence from my attorney, Mr. Muse, on several issues and 
I respectfully decline to answer these questions or any further 
questions based on my Constitutional right.
	MR. WHITFIELD.  So you are refusing to answer the question on 
the basis of your Fifth Amendment rights, and is it your intent to 
invoke your Fifth Amendment rights in response to any other 
questions we may ask you today?
	DR. SUNDERLAND.  It is with great regret that I say yes to that 
question.
	MR. WHITFIELD.  Then you are excused from the witness table 
at this time but I advise that you remain subject to the process of 
the committee and that if the committee's need is such, then we 
may recall you.
	DR. SUNDERLAND.  Yes, sir.  Thank you.
	MR. WHITFIELD.  Dr. Putnam, my next question for you is this.  
Mrs. Putnam, according to NIH records involving you, there were 
2,132 vials of spinal fluid shipped to Pfizer in connection with a 
known biomarker project representing samples from 538 subjects 
and about 14 different protocols but there were about 1,100 vials 
shipped in connection with the unknown biomarkers or discovery 
research project.  Do you know if there is data showing how many 
subjects are represented in those samples and from what protocol 
numbers?
	MS. PUTNAM.  Upon the advice of my attorney, I will assert my 
Fifth Amendment privileges and respectfully decline to answer.
	MR. WHITFIELD.  So Ms. Putnam, you are refusing to answer 
the question on the basis of the protections afforded to you under 
the Fifth Amendment of the U.S. Constitution?
	MS. PUTNAM.  Yes.
	MR. WHITFIELD.  And you would invoke that Fifth 
Amendment right on any additional questions that we may ask you 
today?
	MS. PUTNAM.  Yes, sir.
	MR. WHITFIELD.  Then you also are excused from the witness 
table at this time but I would advise you that you remain subject to 
the process of the committee and that if the committee's need is 
such, we may recall you at some future time.  Thank you.  At this 
time I would like to call up the single witness in the third panel, 
and that is Dr. Michael Gottesman, who is the Deputy Director for 
Intramural Research at the National Institute of Health.  Dr. 
Gottesman, thank you very much for being with us today.  We 
appreciate your time.  We look forward to your testimony.  As you 
know, this is an investigating oversight committee hearing and it is 
our process to take testimony under oath.  Do you have any 
objection to testifying under oath today?
	DR. GOTTESMAN.  No, I do not.
	MR. WHITFIELD.  And do you have legal counsel with you 
today?
	DR. GOTTESMAN.  No, I do not.
	[Witness sworn]
	MR. WHITFIELD.  You are now under oath, and we recognize 
you for your 5 minute opening statement.

STATEMENT OF MICHAEL M. GOTTESMAN, M.D., DEPUTY DIRECTOR FOR INTRAMURAL 
RESEARCH, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN 
SERVICES

	DR. GOTTESMAN.  Thank you, Mr. Chairman, Mr. Stupak and 
members of the subcommittee.
	I am Dr. Michael Gottesman, the Deputy Director for 
Intramural Research at the National Institutes of Health, an agency 
with the U.S. Department of Health and Human Services.  I am 
responsible for oversight and coordination of intramural research, 
training, and technology transfer activities conducted within the 
laboratories of the 22 intramural research programs of the NIH.  So 
in that sense, I am that person who oversees both the research and 
the policies that keep NIH researchers out of trouble.
	The intramural program represents about 10 percent of the total 
NIH budget, or $2.8 billion in fiscal year 2006.  Our 6,000 
intramural scientists work in an environment where creativity is 
encouraged and cutting-edge research is the norm.  Discoveries 
such as the first effective chemotherapy for childhood leukemia 
and Hodgkin's disease and the use of AZT to treat AIDS were 
developed in the clinical center at the NIH.
	The NIH intramural research program could not succeed nor 
could any scientific endeavor without collaborative interactions 
between our scientists and scientific investigators in academic 
research institutions and in private industry.  Such collaborations 
are encouraged as you have heard.  Without them, the pathway to 
discovery would likely be slowed by innumerable obstacles and 
many of our greatest research achievements might not have 
occurred.
	Of course, policies intended to facilitate collaborations between 
Federal and private-sector researchers must be firmly grounded in 
ethical principles.  The NIH leadership was reminded of the 
importance of this principle 2 years ago by this subcommittee, and 
in your recommendations, we realize that there were many areas in 
which we could improve our oversight.  Your recommendations 
prompted NIH and the Department of Health and Human Services 
to revisit and dramatically strengthen ethics regulations, as you 
know, in 2005.  New department regulations addressed 
vulnerabilities of the NIH ethics system by completely banning all 
personal or outside consulting by NIH scientists with 
pharmaceutical and biotechnology companies.  Private outside 
consulting on subjects that are the same or similar to an 
employee's official duties has always been prohibited, as you have 
heard, even under previous regulations.  The events under 
consideration at today's hearing occurred before these new 
regulations were issued, the ones absolutely banning consulting 
arrangements.  The subcommittee has understandable concerns 
about the transfer of human biological samples from NIH to the 
private sector in connection with the consulting arrangement.  NIH 
shares these concerns.
	First and foremost, we want to know if important biological 
samples were transmitted without adequate controls and if human 
subject protection requirements were met.  Second, we want to be 
sure that our internal controls on biological samples are consistent 
with all requirements including the regulation governing outside or 
personal activities.
	Regardless of the outcome of the multiple reviews concerning 
this matter, I would like to be perfectly clear about NIH's position.  
Any attempt to illegally profit from official research activities, 
especially where human biological materials are involved, is 
totally unacceptable.  Engaging in such an activity is a violation of 
NIH core ethical principles past and present.  We cannot tolerate 
such behavior since it undermines the credibility of NIH as an 
unbiased source of scientific information.  I am told that the 
material in question, spinal fluid taken from Alzheimer's disease 
patients, was provided by an NIH intramural scientist to a 
pharmaceutical company.  This transfer of human tissue samples 
has raised numerous issues and concerns including the adequate 
protection of the rights of individuals who participate in clinical 
trials, alleged conflict of interest, and intellectual-property issues.  
These areas of oversight involve complex regulations and 
interactions that need to be clarified, and I think Dr. Insel's chart 
was just the beginning of the complexity of the issue.
	What can we do to assure that problems such as this do not 
recur?  In addition to the reforms implemented in our ethics 
program, we are enhancing policies pertaining to the handling of 
human tissue samples and related intellectual property.  While 
sharing such materials facilitates and accelerates the scientific 
process, it is also clear that additional protections must be in place 
when scientists share tissue samples including blood, serum or, in 
this case, cerebrospinal spinal fluid.  Accordingly, after reviewing 
our policies and procedures regarding the transfer of such 
materials, we determined that further clarification is necessary and 
we are taking the following steps.
	Number one, NIH will provide guidance to investigators on the 
different mechanisms including MTAs, letters of collaboration, 
and cooperative research and development agreements available 
for entering into collaborations and transferring materials outside 
of the NIH, and we will require that all transfers of samples 
derived from human subjects must use a written mechanism so 
there will be no transfer without a written mechanism.  NIH will 
clarify that in cases involving the transfer of material derived from 
human subjects, all such written agreements must be accompanied 
by more-rigorous checks and balances including the review and 
approval by senior leadership at the relevant institute, so an 
investigator on his own cannot arrange to transfer these samples.
	NIH has initiated a comprehensive review of policies across 
NIH involving MTAs to determine if additional requirements are 
necessary in the case of MTAs that do not involve the transfer of 
material derived from human participants.  I just want to point out 
that most of our transfers are of laboratory-derived research tools, 
pieces of DNA or cell lines or antibodies, things like that, that 
don't directly affect human subjects or clinical research.
	NIH has also reviewed its policies governing the use of stored 
human tissue samples.  Stored human tissue samples if identifiable 
by codes or other identifiers are considered human subjects under 
applicable Federal regulations.  Research uses of previously 
collected and stored human samples when intramural research 
program investigators can personally identify the sources must be 
prospectively reviewed and approved by an institution review 
board.  This is not negotiable.  IRBs are charged by Federal 
regulation 45 CFR part 46 with reviewing research protocols to 
protect the rights and safeguard the welfare of research 
participants.  When reviewing a proposed new research use of 
stored samples, an IRB will consider the original research use and 
carefully consider the informed-consent document in order to 
determine if the new use is consistent with the original protocol.  
We believe the process for reviewing uses of stored samples must 
be clear and rigorous.  In order to assure that all NIH intramural 
research program researchers understand the requirements for the 
research use of stored samples, the following steps will be or have 
been taken.
	A memorandum has been sent to all intramural clinical 
researchers, clinical directors, and scientific directors clarifying the 
oversight requirements for the collection and research use of 
human samples, data and specimens.  The clinical center's Medical 
Executive Committee, which consists of the clinical directors and 
some other leading scientists in all the institutes, implemented 
procedures to assure that all clinical center protocols receive 
continuing NIH IRB review and approval as long as research 
analyses using coded samples continues.  So if a protocol is closed 
but the samples are still valuable, in order to use those samples you 
need continuing review and approval by an IRB.
	NIH will modify its standard MTA form to include language 
indicating that the transfer of either coded or identifiable samples 
has been reviewed by an IRB or exempt from IRB review pursuant 
to 45 CFR 46.  All research protocols in which intramural 
researchers intend to collect and store human samples, specimens, 
or data must include a detailed description of the intended use of 
the samples including any proposed future use, even after 
termination of the protocol.  Consent documents must include 
relevant language.  While we cannot anticipate all prospective 
uses, we want to ensure that research participants have as much 
information as possible on how their own material will be 
maintained and used.
	While these new rules will establish conditions to prevent the 
recurrence of the problems we have heard about today, in order to 
be fully successful we must be sure that our staff is fully educated 
about these rules, that they have the administrative support needed 
to keep up with the additional paperwork, and we have heard about 
this issue of overloading people with bureaucratic obstacles and 
delaying research.  This can be addressed with administrative 
support and these people can also provide expert advice because 
these are complex regulations.  And if the rules are knowingly 
violated, there will have to be consequences.
	Science is an ongoing process that requires constant review and 
adaptation.  The same is true for NIH's programs that manage the 
research enterprise.  Many of our adaptations result from internal 
review.  Some ensue from external oversight such as the work of 
this subcommittee.  In either case, NIH leadership understands we 
must be responsive.
	Thank you for this opportunity, Mr. Chairman.  I would be 
pleased to answer questions.
	[The prepared statement of Michael M. Gottesman, M.D. 
follows:]

PREPARED STATEMENT OF MICHAEL M. GOTTESMAN, M.D., DEPUTY DIRECTOR FOR 
INTRAMURAL RESEARCH, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH 
AND HUMAN SERVICES

        Good morning Mr. Chairman, Mr. Stupak, and Members of the 
Subcommittee.  I am Dr. Michael Gottesman, the Deputy Director 
for Intramural Research at the National Institutes of Health (NIH), 
an agency within the U.S. Department of Health and Human 
Services (HHS).   I am responsible for oversight and coordination 
of intramural research, training, and technology transfer activities 
conducted within the laboratories of the 22 intramural programs of 
the NIH.  The intramural program represents about 10 percent of 
the total NIH budget, or $2.8 billion in Fiscal Year 2006.   Our 
6000 intramural scientists work in an environment where creativity 
is encouraged and cutting edge research is the norm.   
        The intramural research program provides unique opportunities 
and resources to encourage important high-risk, high impact 
scientific inquiries that may be difficult to pursue in the private 
sector or academia.   Intramural laboratories are regularly 
subjected to rigorous outside reviews.
  	The NIH Clinical Center is the focal point of the intramural 
enterprise, where laboratory scientists and clinicians work in close 
physical and intellectual proximity, providing a unique cauldron 
for translational and clinical research, with the cost of patient 
participation covered by the NIH budget.   The first 
chemotherapeutic cures for childhood leukemia and Hodgkin's 
disease, and the first use of AZT to treat AIDS, resulted from 
research done at the Clinical Center, the largest research hospital in 
the country.   Of the 19 scientists with medical degrees who have 
won Nobel Prizes in Medicine in the past 20 years, nine were 
trained in the intramural program at NIH.
        The NIH intramural research program could not succeed - nor 
could any scientific endeavor - without collaborative interactions 
between our scientists and investigators in academic research 
institutions and private industry in the course of their official work.   
Such collaborations are encouraged.  Without them, the pathway to 
discovery would likely be slowed by innumerable obstacles and 
many of our greatest research achievements might not have 
occurred.
        Of course, policies intended to facilitate collaborations between 
federal and private sector researchers must be firmly grounded in 
ethical principles. The NIH's leadership was reminded of the 
importance of this requirement two years ago by this 
Subcommittee's investigation of consulting arrangements between 
intramural scientists and companies in the pharmaceutical and 
biotechnology industries. Your oversight review prompted NIH 
and HHS to revisit and dramatically strengthen ethics regulations 
in 2005.
        New HHS regulations addressed vulnerabilities in the NIH's 
ethics system by completely banning all personal or outside 
consulting by NIH scientists with pharmaceutical and 
biotechnology companies.  Private outside consulting on subjects 
that are the same as or similar to an employee's official duties has 
always been prohibited, even under previous regulations.  The 
events under consideration at today's hearing occurred before these 
new regulations were issued.   It is a sensitive matter that is still the 
subject of ongoing review.
        The events are connected to research on Alzheimer's disease, 
specifically attempts to identify biomarkers that identify the early 
presence of the disease.  This research is one of the most important 
areas of investigation regarding Alzheimer's disease and should be 
pursued with vigor.  But the quest for biomarkers by NIH must be 
conducted according to Federal rules pertaining to human subjects 
protection, intellectual property, and conflicts of interest.
As I understand it, the Subcommittee has specific concerns 
about the transfer of human biological samples from NIH to the 
private sector in connection with a consulting arrangement.   NIH 
shares these concerns. 
        First and foremost, we want to know if important biological 
samples were transmitted without adequate controls and if human 
subject protection requirements were met.
Second, we want to be sure that our internal controls on 
biological samples support the application and enforcement of all 
requirements, including the regulation governing outside or 
personal activities.
        Regardless of the outcome of the multiple reviews concerning 
this matter, I want to be perfectly clear about NIH's position.  Any 
attempt to illegally profit from official research activities, 
especially where human biological samples are involved, is totally 
unacceptable.  Engaging in such an activity is a violation of NIH's 
core ethical principles, past and present.  We can not tolerate such 
behavior.
        I am told that the material in question - spinal fluid taken from 
Alzheimer's disease patients - was provided by a NIH intramural 
scientist to a pharmaceutical company.   This transfer of human 
tissue samples has raised numerous issues and concerns, including 
the adequate protection of the rights of individuals who participate 
in clinical trials, alleged conflict of interest, and intellectual 
property issues.   These areas of oversight involve complex 
regulations and interactions that need to be clarified.	
With this principle in mind, on August 25, 2005, HHS, with the 
concurrence of the Office of Government Ethics, published a final 
rule governing standards of ethical conduct for NIH employees.  
The new regulation contains the following additional provisions:
         All NIH employees are now prohibited from engaging in 
outside employment with pharmaceutical companies and 
biotechnology companies.   
	 The extent to which the most senior NIH employees may hold 
certain types of stock and other financial interests is severely 
limited. 
	 The number of employees required to disclose financial 
interests is significantly expanded.
        In addition to the reforms implemented in our ethics program, 
we are enhancing policies pertaining to the handling of human 
tissue samples and related intellectual property.   While sharing 
such materials facilitates and accelerates the scientific process, it is 
also clear that additional protections must be in place when 
scientists share human tissue samples, such as blood, serum, or as 
in this case, cerebrospinal fluid.   Accordingly, after reviewing our 
policies and procedures regarding the transfer of such materials, 
we determined that further clarification is necessary.  In order that 
NIH employees understand that formal mechanisms such as 
Material Transfer Agreements (MTAs) are required when human 
research materials are transferred, we are taking the following 
steps: 
	 NIH will provide additional guidance to investigators on the 
different mechanisms available for entering into collaborations 
and transferring materials outside of the NIH.  While we 
thought that the current rules were clear to most scientists, we 
think it is necessary to clarify that a MTA should be used when 
transferring materials.  Scientists should use research 
collaborative agreements, or Cooperative Research and 
Development Agreements (CRADAs), when entering into 
research collaborations with industry.
	 NIH will require that all transfers of samples derived from 
human subjects must involve a written mechanism - MTA, 
CRADA, letter of collaboration, or other agreement.  Such 
agreements must be in writing to ensure compliance with all 
requirements regarding human subjects protections.  Further, 
the use of written mechanisms will permit NIH to track the 
sharing of clinical samples with outside entities, and monitor 
compliance with the policy. 
	 NIH will clarify that in cases involving the transfer of 
material derived from human subjects, all such written agreements must 
be accompanied by more rigorous checks and balances, 
including the review and approval by senior leadership at the 
relevant Institute.    
	 NIH has initiated a comprehensive review of policies across 
NIH involving MTAs to determine if additional requirements 
are necessary in the case of MTAs that do not involve the 
transfer of material derived from human participants.   NIH 
policy requires the widespread dissemination of research tools.  
It is not clear, however, that such enhanced protections should 
be required for all materials, such as laboratory-produced DNA 
samples, cell lines, and antibodies, whose main function is to 
accelerate research.  A further analysis is necessary to inform 
policy development in this area.    

        NIH has also reviewed its policies governing the use of stored 
human tissue samples.  Stored human tissue samples, if identifiable 
by codes or other identifiers, are considered "human subjects" 
under applicable Federal regulations.  The intramural research 
program's human research protection program functions under a 
Federal-Wide Assurance (FWA) with the HHS Office for Human 
Research Protections (OHRP).  Its FWA commits the intramural 
program to conduct its human subjects research activities 
consistent with acceptable ethical principles and in compliance 
with 45 CFR part 46, the regulation governing the protection of 
human subjects in research.  I am responsible for implementing the 
FWA, and the Office of Human Subjects Research (OHSR) within 
the Office of Intramural Research serves this purpose.
        Research uses of previously collected and stored human 
samples, when intramural research program investigators can 
personally identify the sources, must be prospectively reviewed 
and approved by an Institutional Review Board (IRB).  IRBs are 
charged by federal regulation (45 CFR part 46) with reviewing 
research protocols from the vantage point of protecting the rights 
and safeguarding the welfare of the research participants.  When 
reviewing a proposed new research use of stored samples, an IRB 
will consider the original research use and carefully consider the 
informed consent document in order to determine if the new use is 
consistent with the original protocol.  If the research is subject to 
regulation by the Food and Drug Administration (FDA) (for 
example, if an investigational diagnostic test is being studied), then 
the IRB would also apply FDA regulations.  We believe the 
process for reviewing new uses of stored samples must be clear 
and rigorous. In order to assure that all NIH intramural research 
program researchers understand the requirements for the research 
use of stored samples, the following steps have been or will be 
taken:  
	 A memorandum has been sent to all intramural clinical 
researchers, clinical directors, and scientific directors 
clarifying the oversight requirements for the collection and 
research use of human samples, data and specimens.  
	 The Clinical Center's Medical Executive Committee 
implemented procedures to assure that all Clinical Center 
protocols receive continuing NIH IRB review and approval as 
long as research analyses using coded samples continues.
	 NIH will modify its standard MTA form to include language 
indicating that the transfer of either coded or identifiable 
samples has been reviewed by an IRB or is exempt from IRB 
review pursuant to 45 CFR part 46 as determined by OHSR.  
This step will assist technology transfer staff in determining 
whether the scientist has adhered to human subjects 
requirements. 
	 All research protocols in which intramural researchers intend 
to collect and store human samples, specimens, or data must 
include a description of the intended use of the samples; how 
the samples will be tracked; how they will be stored; what will 
happen to the samples at the completion of the protocol; what 
circumstances would prompt the investigator to report to the 
IRB loss or destruction of samples, and any proposed future 
use (i.e., use after termination of the protocol).  Consent 
documents must include relevant language.  While we cannot 
anticipate all prospective uses, we want to ensure that research 
participants have as much information as possible on how their 
own material will be maintained and used.  

        These steps will help ensure that investigators fully understand 
NIH requirements for the research use of previously collected, 
stored human samples, and that proposals for such uses must be 
approved by an IRB and by OHSR.  
        Science is an ongoing process that requires constant review and 
adaptation. The same is true for NIH's programs that manage the 
research enterprise.  Many of our adaptations result from internal 
review.  Some ensue from external oversight, such as the work of 
this Subcommittee. In either case, NIH's leadership understands 
we must be responsive.
        Sometimes the problems identified by internal and external 
oversight are systemic, but sometimes they result from individual 
behavior.  To the extent NIH identifies systemic issues, we will 
take appropriate action.    In the case of individual misconduct, we 
will seek remediation, including dismissal, where warranted.  
        Thank you for this opportunity, Mr. Chairman. I will be 
pleased to answer your questions.

	MR. WHITFIELD.  Dr. Gottesman, thank you very much for 
your testimony, for being here today.  First of all, as the Deputy 
Director for Intramural Research, I would like for you to explain as 
if you were addressing maybe a rotary club in Leesburg, Virginia, 
exactly the process that you need to go through if one of your 
research scientists at, say, the National Institute of Mental Health, 
came to you with a collaborative agreement and wanted to enter 
into a collaborative agreement with some third party.  Could you 
just kind of walk us through the steps that would be necessary to 
clear that?
	DR. GOTTESMAN.  Yes.  First of all, when you said come to me, 
you mean come to the appropriate authority at the institute?
	MR. WHITFIELD.  Yes.
	DR. GOTTESMAN.  So when we engage in cooperative research 
and development agreements or so-called CRADAs which are the 
most formal of our agreements with companies, sometimes the 
agreement is initiated by an investigator who is aware of interests 
that accompany or somebody else may have in the product.  
Oftentimes it results from advertising.  We actually have adverse 
research opportunities at the NIH and most often if there is an 
opportunity to develop a specific idea or a product, our technology 
development people will meet with the scientists, understand the 
scope of the project and then advertise that there are opportunities 
for other companies and then people apply for that opportunity.  
They are interviewed entirely by the technology development 
coordinators within the institute.  At this point the investigator is 
not involved in the discussions in terms of negotiations except as 
an advisor on the scientific aspects of the research.  After some 
discussions, a document is drawn up which describes in detail the 
nature of the collaboration and we require--there is a whole set of 
rules that cover what we will allow and what we won't allow.  For 
example, NIH does not do research for hire.  If a company wants 
us to do research for them, we generally won't do that unless it is 
clear that that is jointly desirable from the point of view of moving 
science forward.  There is a bunch of rules and there is a policy 
that covers that.  I am sure the committee is aware of that.  After 
those discussions, there is review internally, a document which 
includes a conflict of interest review in which questions are asked 
about whether the scientists involved in the research have any 
outside personal activities with the organization, and if they 
respond that they don't and our review indicates that that is correct 
and we do--the deputy ethics counselors at each of the institutes 
does review using Internet searches and so on.
	MR. WHITFIELD.  So they have to file a form that--
	DR. GOTTESMAN.  There is an extensive document which is the 
CRADA application form which includes something called a 
conflict-of-interest evaluation.  It is not only a statement by the 
scientist but it is also a request--there is a process in which the 
institute actually looks into that statement.  As you know, we are 
developing a better electronic system for tracking all of the 
different activities of our scientists and that will be an enormous 
help in researching whether or not there is or is not conflict of 
interest.  If the institute is interested in moving forward, the 
recommendation goes to a central committee, which is the 
cooperative Research and Development Committee, which reports 
to me.  There is a chair, and that committee reviews and 
determines whether the CRADA is in keeping with NIH CRADA 
policy, makes a recommendation.  Sometimes some of the points 
of the CRADA need to be negotiated.  And then that goes back to 
the institute.  It gets renegotiated.  It comes back for discussion.  
Our legal counsel, the Office of Technology Transfer, signs off and 
I actually sign off centrally as DDIR on all those documents.  So it 
is a very formal, very careful process to guarantee that there is no 
conflict of interest, that the research is in the interests of the people 
of this country and that it is scientifically important to move ahead.
	MR. WHITFIELD.  The institute from which it comes is 
involved, the Office of Intramural Research, and the Office of 
Technology Transfer is involved.  Did I miss any other--
	DR. GOTTESMAN.  Well, my office, the Office of Intramural 
Research, the Office of Technology Transfer, the technology 
development coordinators within the institutes, the committee, the 
CRADA committee.  Many people.  And the deputy ethics 
counselor who reviews the conflict-of-interest statement.  So I 
would say from my point of view, this is a model system.  It 
obviously takes some time to negotiate these agreements and it is 
possible during that interim period if there is a partner who is 
anxious to get research going to have a letter of collaboration 
which precedes a cooperative research and development agreement 
to allow research to move forward.
	MR. WHITFIELD.  Are there additional safeguards put into these 
collaborative agreements when human tissue samples are involved 
or not?
	DR. GOTTESMAN.  Only to the extent that we have human 
subjects regulations that I have mentioned that kick in.  We have a 
requirement that if there is a CRADA involved in the study, that 
the IRB be informed about the CRADA, know how the partners 
are and so on.  So we are beginning to make these connections 
between the different oversight parts of the NIH.
	MR. WHITFIELD.  So the consent forms that donors sign in 
providing human tissue samples to the institute, they disclose 
suppose in a rather broad way how this material can be used?
	DR. GOTTESMAN.  So, Mr. Chairman, if you are speaking about 
the consents that the patients--
	MR. WHITFIELD.  Yes.
	DR. GOTTESMAN.  Yes.  So the process of informed consent 
has been one of the key features of the development human 
subjects' protections.  I would say that in the early 1990s when 
many of the protocols were being conducted that we are talking 
about here, the consent forms were not very specific and in fact, in 
reviewing for this hearing I looked at some of the consents that 
were used in this case and it is clear that the patients were being--
that subjects that were being asked to sign off very generally on 
use of materials.  That kind of general language would not be 
allowed in the current environment.
	MR. WHITFIELD.  Now, there has been some discussion today 
about the necessity or the need for a central protocol that would 
extend throughout NIH, particularly relating to human specimen 
repositories and so forth, but the impression that I get from 
testimony is that every individual institute already has pretty 
stringent protocol for tracking this.  Is there a real need for a broad 
policy throughout NIH or is it better to have each institute take 
care of that?
	DR. GOTTESMAN.  So by tradition, scientists have always 
controlled their own research activities and resources in the sense 
that they by virtue of the requirements under our research integrity 
program are responsible for keeping adequate records for storing 
samples in an appropriate way, for using these samples under all 
appropriate rules and regulations.  This is part--Dr. Insel 
mentioned that some of the system is based on trust, and 
traditionally at the NIH and in all scientific institutions, the 
individual scientific investigator has had that responsibility.  One 
of the ways in which we are dealing with whether or not those 
responsibilities are being exercised appropriately is to make sure 
that samples aren't used for purposes other than the original 
intended purpose under the approved protocol by requiring all the 
different steps that I have mentioned.
	I think probably what is most important is that NIH has been 
thinking very hard about ways in which we could optimize the use 
of these samples.  As you point out and as many of committee 
members have pointed out, these are very valuable materials.  They 
are unique in the sense that at no time or place will that individual 
ever be able to give that sample again if you are looking at a 
longitudinal study and somebody is being studied over 10 or 20 
years and many of the NIH studies are long-term studies.  The 
sample that goes back 20 years as a predictor of a disease to come 
is a very important sample and not easily reproduced although you 
could reproduce the whole study.
	So we really want to be sure that these samples are used 
appropriately, and one of the things that NIH has been working on 
in keeping with actually the desire of the whole Federal 
government to create a much more electronic database for medical 
and clinical issues is, you know, what does it take to make the 
system entirely electronic so it is easily queried and you can use 
materials easily, and we started actually by developing a clinical 
research information system which took about 5 years and is now 
in place in the clinical center which tracks all patients' medical 
records, their test results and their images, their X-rays and so on 
so that it is possible now, and I invite you all to visit the clinical 
center, to stand at a patient's bedside and get electronic 
descriptions of what they are doing.  This is the kind of futuristic 
view of medicine I think NIH is actually taken the lead in this.  
Each of the institutes is developing in their own way clinical 
research tools to be able to analyze their specific clinical trials, and 
as it turns out--I had mentioned we have 22 intramural programs.  
About 17 of them do clinical research.  And the type of clinical 
research differs substantially amongst the institutes so each has 
different needs and a few different protocols are being developed.  
I just spoke to one of our scientific directors who spent 4 years 
developing a data set, a tracking program for clinical samples, 
clinical trials, clinical questions that are being asked in the institute 
within one of the institutes and we talked about the feasibility of 
making that more generally available and I think that will begin to 
happen.
	I think we are still up against a bit of a technical problem.  The 
number of samples involved is overwhelming and we are not 
talking about, you know, putting bar codes on them as they come 
in.  We are talking about going back 20, sometimes 30 years and 
we are talking about millions of samples at the NIH.  So this is a 
big task but I think it is a laudable goal both from the oversight 
point of view and also because what it does is, it makes available 
these potential data sets to people who have a new idea for 
research.
	MR. WHITFIELD.  My time has expired.  I recognize Ms. 
DeGette.
	MS. DEGETTE.  Thank you very much, Mr. Chairman.  Dr. 
Gottesman, I want to ask you some questions that I also talked to 
Dr. Insel about and the first one is, that--and by the way, I applaud 
your determination to raise the bar here.  I think it is important and 
I think we would all agree.  And the Chairman was also alluding to 
what I talked to Dr. Insel about which is, we are getting ready to do 
NIH reauthorization in this committee and Dr. Zerhouni wants 
more centralized decision-making that would then take the inter-
institute cooperation to a higher level which I think is a good idea.
	But my question is, it seems to me that the physical tracking of 
these tissue samples, and heaven knows what else that we are 
keeping at NIH, is at a very rudimentary level, and if we are going 
to have more cross-institute cooperation, which I think is really the 
cutting edge of medical research, how on Earth can we hope to 
achieve those laudable goals if we don't really make a push for 
much better cataloging and much better cross-referencing?
	DR. GOTTESMAN.  I agree with you, and I think that--
	MS. DEGETTE.  Well, how can we do it?  Do you--
	DR. GOTTESMAN.  Well, I mean, I have a variety of authorities 
and I also have ability to persuade people above and beyond my 
authority.  So in terms of tracking samples as the institutional 
official human subjects' research, I can require that we know that 
every sample has been approved by an IRB before it gets used, 
before it gets sent out and so on.  In terms of the requirement that 
there be scientific tracking programs, electronic databases, there I 
use my persuasive powers to make it clear that these are important 
scientific as well as management issues for our scientific directors.  
We hold them responsible.  I delegate to them responsibility for 
tracking human samples, making sure they are properly used, and 
under that authority, I can ask them to make sure that they know 
where the samples are.
	MS. DEGETTE.  But do you intend to have some kind of a 
standard protocol throughout the institutes that other people can 
access?
	DR. GOTTESMAN.  Well, as I said, the needs of each of the 
institutes are somewhat different.  The type of protocols that are 
carried on at NIMH and the Cancer Institute are really quite 
different in kind.
	MS. DEGETTE.  Right, but what I am saying is, if you have a 
bunch of tissue samples at those two institutes, just cataloging 
what you have got there and what people are using, that is not 
different.
	DR. GOTTESMAN.  No.  So there is a term in computer 
networking called interoperability.
	MS. DEGETTE.  Yes, I know that.
	DR. GOTTESMAN.  And if we let 1,000 flowers bloom and we 
say everybody needs to develop a system for tracking and we don't 
require that those systems talk to each other, then we have a 
problem.
	MS. DEGETTE.  Sir, this is exactly what I am saying.
	DR. GOTTESMAN.  The advantage we have at NIH is, we have a 
central clinical center which is really supported by taps on each of 
the institutes.  That clinical center has a database that I mentioned 
which includes all the different--
	MS. DEGETTE.  And how long has that been in place?
	DR. GOTTESMAN.  It is about a little over a year.
	MS. DEGETTE.  So that was not in place when the--
	DR. GOTTESMAN.  No, no.
	MS. DEGETTE.  Would that system have--right now if 
something like this happened now, would that system stop it?
	DR. GOTTESMAN.  No, that system doesn't track clinical 
samples but--
	MS. DEGETTE.  So what are we going to do to stop it?
	DR. GOTTESMAN.  In order for an investigator to be able to use 
that system with respect to their clinical samples, it would need to 
be interoperable so that the fact that we have invested so much in 
the central system will really force the interoperability of the other 
systems.  They won't be useful to our scientists unless they can 
interact with the central system.  So what I am saying is that--
	MS. DEGETTE.  Okay.  You know, I--
	DR. GOTTESMAN.  --we are heading in the right direction.
	MS. DEGETTE.  Okay.  I may follow up with some more 
questions because I frankly don't understand what you are saying.  
I want to talk to you about this chart.  I am sure you have seen this, 
the one that Dr. Insel gave us, and I think it is all swell that we 
have all of these cross checks and so on, but as I was sitting here 
looking at this chart, if somebody wanted to take some tissue 
samples and just go outside the chart around the arrows, there is 
nothing in here that would prevent that from happening.  If 
someone just wanted to do that--I mean, within the institutes--I 
think this is great, the IRBs, the board of scientific counselors, the 
Office of Technology Transfer and so on.  If someone just wanted 
to take those tissue samples out, go to a pharmaceutical company 
and profit on the side, this system would not have a safeguard.  
Wouldn't you agree?
	DR. GOTTESMAN.  Yes.  So what you are saying is that if 
somebody--if we say what the rules are and somebody willfully 
breaks those rules by not reporting--
	MS. DEGETTE.  Right, which is what happened in this case.
	DR. GOTTESMAN.  Or taking samples and not reporting that 
they have used them for that purpose.
	MS. DEGETTE.  Right.
	DR. GOTTESMAN.  There is nothing in the current system that 
would prevent that.
	MS. DEGETTE.  Right.  Even in this beefed-up system.
	DR. GOTTESMAN.  And I am hard pressed in any kind of 
enforcement process to be able to answer how to prevent an 
individual from doing that except to say that there needs to be 
some sort of auditing function tied in to all of these processes so 
that we know maybe not for every person who is involved but on a 
representative basis how it is that the system is working.
	MS. DEGETTE.  Well, I have two suggestions.  Number one is, 
if you beef up your tissue tracking system which we can talk about 
more later, then even if somebody is going out beyond that, if they 
take the issue samples out, you have got some kind of computer 
model that would say well, where did they go, they didn't go over 
to another institute or something, that would be a double check.  
The second--because the evidence is gone.  I used to do a lot of 
criminal work in practicing law, and if somebody went to the 
evidence vault at the police department and checked the evidence 
out, then it didn't show up where it was supposed to show up, then 
you knew there was a problem.  That is very simplistic but it is the 
same type of thing.  And the second suggestion I would make is 
that if there is somebody who is so guilty of such gross 
malfeasance as in this case, one might want to think about how the 
personnel rules at the NIH could be modified so they could be fired 
before 2 years were up, because he is still there even after this 
happened.  I don't know if you want to comment on any of that.
	DR. GOTTESMAN.  Well, the only comment I would make and I 
know there is confusion about the various appointment authorities 
at the NIH, civil service versus Commissioned Corps, the 
Commissioned Corps is a separate authority.  It is a uniform 
service and they run their operations similar to the uniform military 
code and they make determinations about hiring and firing people 
and we do not control that at NIH.
	MS. DEGETTE.  And we might want to look at that.  My next 
question is around the informed consent that the people who 
originally donated these tissues for, and again, Mr. Chairman, I 
would ask unanimous consent to submit the consent form for the 
record.  And I am sure you have seen this.  You might even have 
it--you are being handed it.  Okay.  This is the original consent 
form that was used for Dr. Molchan's study, and it seems to me--I 
looked it over and it seems to me fairly specific--you were talking 
earlier about you really need to look at the informed consent and 
have it be specific and have it be full, and I support that 
completely.  But it looks to me like in this situation, the informed 
consent was quite specific and quite thorough for the research 
study that Dr. Molchan was saying she was conducting.  Wouldn't 
you agree with me?
	DR. GOTTESMAN.  Well, in one sense, yes, but let me point out 
something in the informed consent that perhaps you didn't notice 
which changes the tone of it.  At the end of the first paragraph, 
"We hope to obtain information on changes in hormones and brain 
chemicals"--that is very broad-"that occur in Alzheimer's disease 
and in depression."--my goodness, that is huge-"as well as clues 
to the mechanism of the action of lithium."  It makes it sort of clear 
that anything goes, and that is why I think an IRB in looking at this 
currently would just say this is not acceptable--you can't ask 
somebody to sign off on something like--
	MS. DEGETTE.  All right.  So even though there is a lot in 
there, it is that phrase that--
	DR. GOTTESMAN.  It is that phrase.
	MS. DEGETTE.  So it is an interesting dichotomy, isn't it, 
because on the one hand you want to have an informed consent 
that is specific exactly to the research study but then on the other 
hand, what do you do later on if somebody wants to make a 
secondary use of these tissues?  Do you have--and frankly, as Dr. 
Insel pointed out, with Alzheimer's or many other diseases, it is 
likely the donor might already be dead.  So how are you going to 
go back--do you think you go back and get a second informed 
consent or do you think somehow you draft this form so it is both 
specific enough to deal with this research study but broad enough 
to let you use the tissues later?
	DR. GOTTESMAN.  Right.  So we have two new requirements I 
think that will clarify that point.  The first is that is absolutely 
essential in writing up a new protocol to specify not only the intent 
of the protocol, what the study is about, but what will happen with 
the samples--how they will be stored, how long they will be kept, 
what will happen if somebody wishes to use them for another 
purpose, would there be re-consent, would there not be and so on.  
And the second point has to do with the requirement for IRB 
review.  If the IRB reviews--for example, if these had gone before 
an IRB for re-review, the IRB would have looked at the original 
consent.  It might have said well, this is so general that maybe 
patients understood that this was going to happen with their 
samples but in fact there is an issue over time that suggests that no 
one could have conceived of the kind of sophisticated analysis that 
we are doing now 13, 14, 15 years ago and that therefore patients 
need to be identified.  In fact, Dr. Sunderland has patients who he 
has followed over the years and are still alive and were involved in 
some of these protocols and maybe they would conclude, although 
I don't know for sure, that there would be a need for re-consent.  
They can either say the risk is very small and therefore the new 
research can move forward, they can waive consent based on the 
fact that they believe that there is no risk to the patients and the 
original consent covered the area, or they can request that there be 
re-consent, and we re-consent patients all the time.
	MS. DEGETTE.  You know, the other thing, and I know it is 
always on a case-by-case basis, but the subjects of this study, even 
though that statement was broad, it said this study is researching 
this.  It didn't say anything about and I give consent for future.  I 
mean, it may be what you might want to look at in some cases is 
having people give specific consent for this study and then 
developing a secondary consent form that you could have and you 
can use these tissues for future use.
	DR. GOTTESMAN.  Well, I would be very delighted to continue 
this discussion with you because these are issues that the NIH is 
struggling with and the entire research community is struggling 
with.
	MS. DEGETTE.  Thank you very much, Mr. Chairman.
	MR. WHITFIELD.  Dr. Gottesman, just as a follow-up on this 
consent, do you really think that most patients care that much 
about how their samples are going to be utilized?
	DR. GOTTESMAN.  Well, there have been studies done on this 
issue, and many patients who are participants in clinical research 
studies, human subjects research studies, are actually enormously 
altruistic and they believe--they trust the scientists who are 
working.  They want them to be able to use the samples to help 
them or to help somebody else and I think maybe the majority of 
people who participate in clinical research feel that way.  On the 
other hand, sometimes they are uninformed about the potential 
risks to them.  If a discovery is made about some aspect of their 
physiology that could affect their insurability or their 
employability, those are really important risks that need to be 
considered and we would like to be able to reassure people that 
even if they can't think of problems, that we will be thinking about 
these things and making sure that samples are not used for 
purposes that could put them at any risk.
	MR. WHITFIELD.  Just a couple of other questions.  In your 
testimony you stated the NIH will accomplish three things.  One, 
you will provide additional guidance to investigations on material 
transfers; two, you will require that all transfers of samples derived 
from human subjects must involve putting it in writing; three, the 
NIH will clarify that in cases involving human transferred material, 
that there will be review and approval by senior leadership at the 
relevant institute.  Now, is that already being accomplished or do 
you have a time guideline for this?
	DR. GOTTESMAN.  Right.  So because this involves changes in 
our technology transfer program, I have more direct authority over 
the human subjects' part because I'm the institutional official.  So 
we are convening a group of administrators and scientists to 
consider all aspects of material transfer at the NIH, transfer from 
laboratories as well as clinical samples.  I will promise this 
committee that those aspects that we promise to do will certainly 
take place, but there may be other changes in our policy as well, 
and we want to be able to release not piecemeal but altogether the 
policy on material transfer at the NIH that everybody understands, 
that everyone adheres to.
	MR. WHITFIELD.  And do you have a general time guideline on 
that?
	DR. GOTTESMAN.  I think we can probably accomplish this 
within a couple of months.
	MR. WHITFIELD.  Now, one other question.  We have talked a 
lot about the collaborative research agreements and we talked 
about the material transfer agreements, and not being familiar with 
either one of them I would like to just ask you this question.  We 
have on Exhibit #2, there is a material transfer agreement by the 
National Institutes of Health, the provider is Trey Sunderland, the 
recipient is Pfizer, which is the case that we have all been focused 
on, and in paragraph three when it talks about how the research 
material will be used, it says, "Research to identify and validate 
protein markers associated with Alzheimer's disease."  Now, is 
that--from your background as a scientist, your experience, is that 
too broad or is that adequate or--
	DR. GOTTESMAN.  Well, I think the problem is that this is a 
material transfer agreement that is not just transferring materials.  
It is specifying a collaborative agreement.  And I think that under 
normal circumstances if this had been thoroughly reviewed by a 
technology development coordinator, the conclusion would have 
been that this is not an appropriate transfer agreement, transfer 
mechanism that--I always prefer to see CRADAs because, as I told 
you, the system is very formalized and works well.  But it could 
have been done under a collaborative agreement with a company, 
but that has to be signed off by the technology people and the 
senior leadership at the NIH.  So the issue here is not whether this 
is specific or not specific.  It is that it is not an appropriate vehicle 
to transfer the materials.
	MR. WHITFIELD.  Okay.  So it is not an appropriate vehicle?
	DR. GOTTESMAN.  I don't believe so, no.
	MR. WHITFIELD.  Well, I will make one other comment, then I 
will recognize Mr. Stupak here.  I want to ask you to do something 
for us.  I would like for you to work with the National Institute of 
Mental Health to report to us on all of the underlying data that Dr. 
Sunderland should have on the GPB shipments to Pfizer that would 
break down by sample in each shipment and the protocol numbers 
so that we can get a more clear understanding of the specifics of 
that because in the conversations that we have had with the various 
people at NIH, we still are a little bit--we are not sure precisely on 
the specifics of this.  In some of the memos I have seen, I know 
that the National Institute of Mental Health referred to 11 percent 
here and eight percent here was used and whatever.  We would just 
like to get a more clear understanding of the exact shipments, the 
protocol numbers and so forth, and how much was utilized as it 
relates to Pfizer with Dr. Sunderland.
	DR. GOTTESMAN.  Mr. Chairman, we will do the best we can to 
get the information.  As you know, there is an ongoing 
investigation and we have been generally instructed by counsel to 
try not to confuse the different investigations, but I certainly would 
like to get you that information and I will work with the people at 
NIH and see if we can make that happen.
	MR. WHITFIELD.  And Exhibit 26 may provide some help to 
you on that as well, so we can give you a copy of that before you 
go.  We will get a copy to you before you go.  At this time I 
recognize Mr. Stupak.
	MR. STUPAK.  Thank you.  Dr. Gottesman, how long have you 
been at NIH?
	DR. GOTTESMAN.  I have been at NIH 31 years.
	MR. STUPAK.  Okay.  In this new position as--
	DR. GOTTESMAN.  In my current position?
	MR. STUPAK.  Yes.
	DR. GOTTESMAN.  Almost 13 years.
	MR. STUPAK.  Thirteen years.  Has this issue ever arose before 
about use of samples and scientists outside?
	DR. GOTTESMAN.  There are a couple different issues.  The use 
of samples for research purposes is a constant area of discussion at 
the NIH and we are constantly making policy and the policy, as I 
said to Congresswoman DeGette, is a kind of moving target.
	MR. STUPAK.  Well, it seems like there was policy for handling 
hazardous materials or samples but not for this here.  Why was--
	DR. GOTTESMAN.  Well, the NIH policy I think is pretty clear 
and that is dictated by all the requirements for human subjects' 
research, that if there is a closed protocol and that somebody wants 
to use a sample, they need to get permission from the IRB to use 
that sample.  There is an oversight responsibility.
	MR. STUPAK.  So here there should have been an IRB and then 
was it 46 CFR 45, was that--that should have been followed?
	DR. GOTTESMAN.  Right.  That is the controlling legislation, 
yes.
	MR. STUPAK.  And that should have been followed, right?
	DR. GOTTESMAN.  That should have been followed.  What was 
not made clear earlier this morning was that actually some of these 
protocols are still open.  Some of the samples were sent under open 
protocols and some of them were sent under closed protocols.  
There were a total of 16 protocols.
	MR. STUPAK.  Right.
	DR. GOTTESMAN.  And 11 of them had been closed prior to the 
period when the samples were sent.
	MR. STUPAK.  So--
	DR. GOTTESMAN.  Five of them are still open and undergoing 
continuous IRB review.
	MR. STUPAK.  Okay.  And then the IRB--it is my understanding 
Dr. Sunderland was head of the IRB, right?
	DR. GOTTESMAN.  At one--during this period he was the chair 
of the IRB, yes.
	MR. STUPAK.  So who would he get permission from then to--
	DR. GOTTESMAN.  The original review and approval of the 
protocols that allowed the samples to be collected were done with 
an IRB chair who was another person.  He was recused--
	MR. STUPAK.  Well, the original samples, I guess there are no 
questions there but then they were moved outside for commercial 
gain, if he is head of the IRB, who would he get his permission 
from?
	DR. GOTTESMAN.  So in the course of reviewing the human 
subjects' materials, we found that in some cases Dr. Sunderland 
did sign off during the continuing review process on protocols in 
which he was a co-investigator.
	MR. STUPAK.  So he should have received permission or 
someone sign off--
	DR. GOTTESMAN.  Someone else should have done that.  That 
was--
	MR. STUPAK.  With this new flow chart, will that work?  I 
mean, really.  I know we had some comments about this.  You are 
talking about this flow chart here, and how does that make--like if 
I am head of the IRB, where do I go then to get my permission?
	DR. GOTTESMAN.  I mean, this is one of the very basic 
principles of the conduct of any human affair.  If it is your business 
which is being reviewed, you don't sit as a chairman on the 
committee that reviews it.
	MR. STUPAK.  So really what it comes down to, it is not this 
colorful chart.  It really comes down to the integrity of the 
individual?
	DR. GOTTESMAN.  Well, and the institution. I mean, that should 
not have been allowed.
	MR. STUPAK.  Right.  But in order to bypass the safeguards that 
any institution puts in whether it is NIH or Congress, it still boils 
down to the individual, whether or not they are going to follow that 
protocol, whether they are willing to take that risk and what is the 
benefit to them, almost like a cost-benefit analysis in a way.
	DR. GOTTESMAN.  Well, as I said to Congresswoman DeGette, 
it is based on trust but at the same point, we can develop oversight 
mechanisms that reduce the likelihood that any one individual will 
absolutely violate the rules.
	MR. STUPAK.  Sure.  You indicated in your testimony to the 
Chairman here that there is still ongoing investigation in this 
matter.  Is that true?
	DR. GOTTESMAN.  Yes, that is true.
	MR. STUPAK.  What area is the ongoing investigation still 
going on?
	DR. GOTTESMAN.  Well, I mean, Dr. Insel mentioned this 
morning that the AG and the Justice Department have shown some 
interest in this case and I don't know the state of--
	MR. STUPAK.  It is nothing else that NIH is doing other than if 
Justice asks for something--
	DR. GOTTESMAN.  Well--
	MR. STUPAK.  --you will provide them with the information?
	DR. GOTTESMAN.  Following a meeting that I had with the 
counsel for this committee, when I was made aware of what I 
thought were problems with the human protections issues, I 
initiated through my own office and through the Office of Human 
Subjects Research a paper investigation of the various paperwork--
	MR. STUPAK.  That investigation is done though, right?
	DR. GOTTESMAN.  It is not completed yet but it is in progress 
and we have already made a report to the Office of Human 
Research Protections about it.
	MR. STUPAK.  You said you met with House counsel here or 
committee counsel, I should say, excuse me.  So were you part of 
the team at NIH that put together the information that the 
committee requested?
	DR. GOTTESMAN.  My involvement was actually minimal.  I 
mean, NIH separates the oversight of the science from the 
management issues related to disciplining scientists, for example, 
but I was involved at one step, which was--there was a committee 
put together to determine whether in fact there was an overlap 
between the outside activity and the official duty activity.
	MR. STUPAK.  Right.
	DR. GOTTESMAN.  It was a committee of scientists.
	MR. STUPAK.  That is a little different than what I am asking.  
This committee had a hearing in 2004 on this issue.  We followed 
it up.  Myself and Mr. Whitfield, Chairman Barton, Mr. Dingell, 
signed a letter in June of 2005 asking for certain information.  
Were you part of the NIH team that helped put together the 
response?
	DR. GOTTESMAN.  Yes.  Actually, our legislative people came 
to my office and gave me the questions and asked if I could help 
get some of the information about what was existing NIH policy.  
The initial questions were about storage of samples, freezer 
stability, and so on, and what were policies concerning oversight, 
and we provided information about human subjects and material 
transfer.
	MR. STUPAK.  And how about the follow-up letter of January 4, 
2006, and January 26, 2006, by this committee, were you part of 
that team that put together those answers?
	DR. GOTTESMAN.  I am not sure what those refer to but--
	MR. STUPAK.  Is there any question as to whether or not the 
human tissue samples collected by NIH scientists using 
government resources are property of the Federal government?
	DR. GOTTESMAN.  There is no question they are property of 
the--
	MR. STUPAK.  Under what authority do you make that 
statement?
	DR. GOTTESMAN.  The legal authority.  I think there is probably 
some place in the legal code--I mean, this is something that every 
scientist who comes to NIH is told:  Every product of your 
research here belongs to the Federal government.
	MR. STUPAK.  Everyone has testified to that but no one can 
point us to the authority.
	DR. GOTTESMAN.  I can certainly have our legal people 
research it and get you an answer to that.
	MR. STUPAK.  Okay.  I mean, the issue came up yesterday too.  
It was asked a couple times.  At the NIH, is there a policy 
regarding data that is over 5 years old?  You know, there has been 
some testimony that Dr. Sunderland indicated that everything was 
purged and therefore the data wasn't available anymore.
	DR. GOTTESMAN.  So our research integrity policy which has to 
do with what scientists are expected to do in terms of maintaining 
their notebooks and their samples and so on states that samples 
need to be kept for 5 to 7 years.  The new requirements from the 
Office of Research Integrity, which is part of the Department of 
Health and Human Services, are fully 7 years and we are in the 
process--and that is a new requirement--we are in the process of 
aligning our requirement with that requirement.  So the department 
requirement will be retention of materials, data, samples for 7 
years.
	MR. STUPAK.  Then what happens to it after that?
	DR. GOTTESMAN.  Then they can be destroyed or--they can't be 
used for purposes other than the intended purpose, but they can 
certainly be destroyed.
	MR. STUPAK.  In this case, with the lithium study, was any of 
that destroyed, any of that data or research information destroyed?
	DR. GOTTESMAN.  I have no idea.  I know at some point there 
was an e-mail which stated that the material had been purged, the 
information had been purged but I don't know if that actually 
happened. 
	MR. STUPAK.  Let me ask you this question, if I may.  The rules 
at NIH concerning consulting between like NIH and scientists and 
private industry I am sure have changed since Dr. Sunderland.  I 
am concerned, however, that the abuses of the system from which 
Dr. Sunderland profited were not only due to lack of regulation but 
in fact the lack of enforcement of this regulation.  How can you 
assure this committee that there is now an appropriate level of 
actual enforcement other than this chart?  I like the chart but it 
doesn't do much for us.
	DR. GOTTESMAN.  Right.  Well, one of the points I made in my 
testimony is, it is not sufficient to make policy.  You have to be 
sure that people understand it, understand the reason for it, have 
support in order to be able to carry out, and know that there are 
consequences if they don't follow it.  And I think that the current 
environment at NIH is much more sensitive to the need for 
oversight and management.  Some mention was made about the 
culture of scientists and the culture of administrators.  I think one 
of the things that I have been working on for sure is convincing 
scientists that management of science is just as important as the 
conduct of their science.
	MR. STUPAK.  Your deputy ethics counselor, that is in place 
now?
	DR. GOTTESMAN.  Yes, so what this represents is--
	MR. STUPAK.  Let me ask you this.  I don't mean to interrupt 
but time is running short.  Does this chart, does it apply to the 
Corps?  We have had testimony that you can't do things about Dr. 
Sunderland because he is part of the Corps.  Would this all apply to 
the Corps also?
	DR. GOTTESMAN.  Yes.  Anyone who is in the Corps who 
works at NIH is subject to all the same rules and regulations.
	MR. STUPAK.  So if I violate whether I am in the Corps or 
whether I am at NIMH but not part of the Corps, if I violate one of 
these rules I could be terminated, I don't need the Corps 
permission then?
	DR. GOTTESMAN.  No.  The problem is that if you are 
appointed in the Corps, the Corps makes the determination about 
whether you can be terminated.
	MR. STUPAK.  But yet this so-called accountability chart, if you 
will, or whatever you want to call it, your chart here, this is going 
to apply to the Corps?
	DR. GOTTESMAN.  The requirements for people who work at 
the NIH are the same whether they are appointed--
	MR. STUPAK.  Corps or civil service or independent--
	DR. GOTTESMAN.  The decision about hiring and firing is made 
by the Corps, not by the NIH.  That is the issue.
	MR. STUPAK.  I just want to make sure the Corps is going to 
accept this.
	DR. GOTTESMAN.  They do and they will.
	MR. STUPAK.  Okay.  Thank you, Mr. Chairman.
	MR. WHITFIELD.  One other question, Dr. Gottesman.  In 
response to Mr. Stupak, you talked about human tissue samples 
can be destroyed after 5 to 7 years.  Is that mandatory or is that 
just--
	DR. GOTTESMAN.  No.  I guess it is an expectation that 
materials--we don't expect them to be retained for more than 7 
years.  In many cases for the clinical samples that obviously 
continue to be valuable samples, they should be maintained and I 
think it an interesting issue.  Most of our scientists will continue to 
keep them, hoard them in their freezers and hoping that they will 
be useful at some future time.
	MR. WHITFIELD.  Yes, because you can freeze these fluid 
samples for I guess forever, right?
	DR. GOTTESMAN.  Well, the issue about actually what the 
lifetime is of these samples in the freezer is a scientific question 
and I think has not been resolved, at least to my satisfaction.
	MR. WHITFIELD.  It depends on what you are going to use them 
for and so forth.  Okay.  Dr. Gottesman, thank you very much for 
your testimony.  We appreciate your being here today and we look 
forward to working with you as we move forward to maintain the 
integrity and the sterling reputation of NIH.  Thank you.  This 
hearing is adjourned.
	[Whereupon, at 12:55 p.m., the subcommittee was adjourned.]


RESPONSE FOR THE RECORD OF THOMAS R. INSEL, M.D., 
DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH, NATIONAL 
INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND 
HUMAN SERVICES



RESPONSE FOR THE RECORD OF WILLIAM FITZSIMMONS, EXECUTIVE 
OFFICER, NATIONAL INSTITUTE OF MENTAL HEALTH,, NATIONAL 
INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND 
HUMAN SERVICES



RESPONSE FOR THE RECORD OF MICHAEL M. GOTTESMAN, M.D., 
DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH, NATIONAL 
INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND 
HUMAN SERVICES



RESPONSE FOR THE RECORD OF DAVID L. FRIEDMAN, PH.D.

The Honorable Bart Stupak
Question(s) for David Friedman, Ph. D.
Formerly with Pfizer, Inc. 
June 13, 2006
Subcommittee on Oversight and Investigations
Hearing entitled: "Human Tissue Samples: NIH Research Policies 
and Practices"

1. In his report to an NIMH internal review board, Dr. 
Sunderland characterized the three-way collaboration 
involving NIMH, Pfizer, and Oxford Glyocsciences, which 
yielded no data or publications for NIMH, as unsuccessful. 
Would you agree with this assessment?

No.  I thought it went quite well in a scientific sense.

2. If the collaboration did indeed produce significant findings, 
why would Dr. Sunderland characterize it as a failure? 
Would he have any reason to think this was the case?

I noticed that you transitioned from "unsuccessful collaboration" in 
(1) to a question of failure to produce significant findings in (2).  I 
think the jury is still out on the general utility of these markers as 
they traverse the validation process.  Pfizer continues to update the 
patent application periodically, perhaps with new and meaningful 
marker data.  That data should be more visible when the patent 
issues.  Perhaps Dr Sunderland felt it was a failure because nothing 
got published.  Perhaps someone should look into that.

3. Did it strike you as odd that Dr. Sunderland did not want to 
be mentioned in publicity associated with the collaboration 
involving OGS? 

Not really, it wasn't exactly clear why, but not of a scientific 
concern.

4. Did Dr. Sunderland ever mention why he did not want to be 
listed? Would there be any reason for a researched 
interested in publication, and involved in a good-faith 
collaboration, to not wish to be listed in publicity of this 
kind?

Not clear to me why.

5. How regularly did Dr. Sunderland visit your lab or OGS 
while you were in charge of the "unknown biomarkers" 
research?

First of all, I wasn't "in charge" of the research as you suggest 
above.  I was the scientific leader, albeit with several layers of 
management above me also on the team (e.g., Michael Silber, 
Steve Williams).  In terms of the regularity of visits, at least 
quarterly at Pfizer, with perhaps one or two additional visits per 
year for special "data-driven" events.
	

  Eiseman, E. and Castillo, J., Handbook of Human Tissue Sources, RAND Monograph Report, 7 
(1999).  See also U.S. Congress, Office of Technology Assessment, New Developments in 
Biotechnology: Ownership of Human Tissues and Cells - Special Report, OTA-BA-337 (March 
1987) at 3.
  Hakimian, R. and Korn, D., "Ownership and Use of Tissue Specimens for Research," Journal of 
the American Medical Association, November 24, 2004, at 2500. 
  Eiseman, E. and Castillo, J., Handbook of Human Tissue Sources, RAND Monograph Report,xvii 
(1999). 
  Id.  The National Bioethics Advisory Commission (NBAC) estimated that as of 1998, more than 
282 million specimens of human biological materials were stored in the United States, accumulating 
at a rate of more than 20 million cases per year.
  Hindin, T., "Technology and Clinical Trials," Applied Clinical Trials, April 2006 at 12.
  Mills, J.F., "Precedents for Good Storage Practice," Applied Clinical Trials, April 2006 at 58.
  Email on "Harmonization and Repositories," from Lana R. Skirboll, Ph.D., Director, Office of 
Science Policy, NIH, October 27, 2005 to various NIH staff.
  Id.
  The current total number of tissue samples at the NIH is unknown.  As the NIH wrote to the 
Committee in a letter dated August 15, 2005: 
	"NIH does not maintain a central listing of all tissue samples in its possession.  Each laboratory 
is responsible for storing and tracking all samples within its possession.  NIH requires that each 
investigator obtaining such samples complete a Human Pathogen Registration Document, [ ], which 
requires information on the principal investigator, the location of the work,  the agent or human 
blood, body fluid or tissue being worked with, and the names of all individuals working with the 
particular material being registered.  The document does not require the investigator to supply the 
number of samples that he/she plans to work with or obtain.  NIH currently has 390 Human 
Pathogen Registration Documents on file for human blood, body fluids, and/or tissues.  Currently, 
663 laboratories maintain human blood, body fluids, and/or tissue samples. [footnote omitted].  A 
total of 2340 employees are registered for work involving human blood, body fluids, and/or tissues.  
It is important to note that these numbers apply only to active research protocols.
	In addition, NIH maintains biorepositories to provide investigators with pathological samples 
for research uses.  Two are maintained by the National Cancer Institute, . . . " 


  Committee staff requested numerous times to interview Dr. Sunderland, but through his attorneys 
he declined to be interviewed. 
  The consulting payments were in addition to sums Pfizer paid Sunderland for speeches or 
discussions with potential prescribers of Aricept and the occasional advisory board participation.  
Those payments added an additional  $311,000 over roughly the same period of time as the 
consulting agreements.  While such payments are now not permitted under the ethics rules, a special 
NIH ethics panel concluded that had Dr. Sunderland requested approval for these speeches, they 
would have been approved under the standards that predated the Committee's investigation and 
resulting reforms.


  In an attached response to an e-mail dated May 12, 2006, from NIH staff to Committee staff, NIH 
stated:
"Where have tissue samples sitting in a freezer that have been collected from patients in an 
intramural trial, whom do these samples belong to?  Still belong to the donor? NIH? Lab scientist? 
Government?  If it does not belong to the government, want explanation of why not.
Tissue samples collected within the intramural program belong to the Federal Government."
  Committee understands from NIH that the NIH has recently made a referral to the OIG-HHS on 
this issue of undisclosed patent applications.
  As discussed later, Ms. Conn believed that the next step in the process was Pfizer sending her a 
copy of the MTA to review.  This matter is discussed in more detail later in the report.
  According to Pfizer records, what remains of the samples represents about half of what was 
shipped by Dr. Sunderland.  Pfizer is "happy to work with NIH to arrange the return of the samples."  
June 6, 2006 e-mail from Daniel Kracov, Esq. (outside counsel to Pfizer) to Committee staff. 
  December 8, 2004, letter from Robert F. Muse, Esq. to Holli Beckerman Jaffe, Director, NIH 
Ethics Office, page 7.
  Id. , page 8.
  Title 45 Code of Federal Regulations, Part 46.
  National Commission for the Protection of Human Subjects of Biomedical and Behavioral 
Research.  The Belmont Report: ethical  principles for the protection of human subjects of research. 
Washington, D.C.:Government Printing Office, April 18, 1979.  U.S. Department of Health and 
Human Services publication GPO 887-809.
  Position Statement, The Ethics and Humanities Subcommittee of the American Academy of 
Neurology, Neurology 1998, 50: 592-595.
  That silence or ambiguity would not have been unusual for most clinical research protocols 
because there had been no requirement to address future uses.  It was not until January 2006 that the 
NIH Office of Human Subjects Research (OHSR) explicitly addressed this issue, revised its 
guidance, and issued "Sheet 14 Guidance on the Research Use of Stored Samples or Data." In that 
guidance, researchers are required to submit a written protocol to an NIH IRB that includes a 
description of how samples will be tracked, how samples will be stored to be protected from loss or 
destruction, plans for samples at the conclusion of the protocol, and what circumstances would cause 
the lead researcher to report a loss or destruction of samples to the IRB.  In discussion with 
Committee staff, the NIH Deputy Director of Intramural Research, whose office includes OHSR, 
stated that this revision occurred in response to the Committee's investigation. 
  David B. Resnik, J.D., Ph.D., National Institute of Environmental Health Sciences (NIEHS) 
Bioethics Bulletin, "Human Research Q&A," Spring 2005, at 2: 
	Question: "I have access to some leftover tissue samples from another investigator's work.  I 
would like to conduct some research on these samples.  Is this research on a human subject?  Do I 
need to submit a protocol to the NIEHS's Institutional Review Board (IRB)?
Short answer: This is not research on a human subject but you still need to contact the IRB before 
using these samples in research, since the samples were taken from human subjects."
  After several months of inquiries by Dr. Molchan, Dr. Sunderland sent 0.5 cc paired spinal-fluid 
samples from eight Alzheimer's disease patients and two elderly normal volunteers to an outside 
researcher.  In his interview with Committee staff, the Director of NIMH raised the issue of whether 
this transfer was in compliance with NIH guidelines along the same lines that questions had been 
raised by Dr. Sunderland's transfer of samples to Pfizer.  Dr. Molchan, however, told the Committee 
staff that the research purpose of the outside researcher was the same purpose (to conduct a lithium 
study) in the study she had not been able to complete.
  Letter dated May 10, 2006, from Daniel A. Kracov, Esq., Arnold & Porter (on behalf of Pfizer, 
Inc.) to Committee staff.
  The NIH recently advised the Committee staff that the internal NIH investigation on human 
subject research issues had identified 16 different studies connected to Dr. Sunderland's transfer of 
human samples to Pfizer.
  For example, in 2005 Dr. Robert Cohen took over as the Principal Investigator for Dr. Sunderland 
in a few of the protocols involved as sources of spinal fluid for Pfizer.
  May 10, 2006, letter from Daniel Kracov, Esq. to Committee staff: "In April 1998, what was 
Pfizer's understanding of Dr. Sunderland's authority to sign an MTA?  In 1998, Pfizer sought to 
confirm Trey Sunderland's authority to enter into the MTA on behalf of NIH.  In this regard, 
Pfizer's Kathy Smith was referred to Kathy Conn at NIH [the NIMH Director for Technology 
Transfer] who, to Kathy Smith's recollection, confirmed that Dr. Sunderland was authorized to 
execute the agreement.  It has been Pfizer's standard practice when dealing with academic 
institutions, including institutions such as NIH, not to accept an investigator's claim to have 
authority to sign an agreement without consulting with an appropriate representative of the 
contracting institution."
  E-mail from Kathryn E. Monaghan [Smith] to Trey Sunderland, March 24, 1998: "Trey, I spoke 
with Kathy Conn today and she also reconfirmed that we can proceed with the MTA immediately 
and work out the CRADA vs. Consult part in due course.  I fedexed various forms of the MTA on 
Friday  -- hope you got them yesterday?"  Exhibit 31.
  E-mail from Gemma Flamberg (NIH) to Alan Slobodin (Committee staff), June 1, 2006. (Exhibit 
37)
  Pfizer, however, did not actually receive any serum from NIMH (March 31, 2006, letter from 
Daniel A. Kracov, Esq. to Committee staff). 

  (Exhibit 38)
  T. Sunderland, "Prospective search for Alzheimer's disease (AD) biomarkers," in Downing, ed., 
Biomarkers and Surrogate Endpoints: clinical research and applications, Proceedings of the NIH-
FDA Conference held on 15-16 April 1999 in Bethesda, Maryland, USA, at 39, 40 (Elsevier, 2000).
 Dr. Sunderland also highlighted this collaboration in a paper he prepared for a 2000 NIMH of 
Board of Scientific Counselors review of research in his branch. 

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