[Senate Hearing 108-559]
[From the U.S. Government Publishing Office]
S. Hrg. 108-559
RAPID BIO-TERRORISM DETECTION AND RESPONSE
=======================================================================
HEARING
before the
SUBCOMMITTEE ON TERRORISM, TECHNOLOGY
AND HOMELAND SECURITY
of the
COMMITTEE ON THE JUDICIARY
UNITED STATES SENATE
ONE HUNDRED EIGHTH CONGRESS
SECOND SESSION
__________
MAY 11, 2004
__________
Serial No. J-108-74
__________
Printed for the use of the Committee on the Judiciary
U.S. GOVERNMENT PRINTING OFFICE
95-240 WASHINGTON : DC
____________________________________________________________________________
For Sale by the Superintendent of Documents, U.S. Government Printing Office
Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; (202) 512�091800
Fax: (202) 512�092250 Mail: Stop SSOP, Washington, DC 20402�090001
COMMITTEE ON THE JUDICIARY
ORRIN G. HATCH, Utah, Chairman
CHARLES E. GRASSLEY, Iowa PATRICK J. LEAHY, Vermont
ARLEN SPECTER, Pennsylvania EDWARD M. KENNEDY, Massachusetts
JON KYL, Arizona JOSEPH R. BIDEN, Jr., Delaware
MIKE DeWINE, Ohio HERBERT KOHL, Wisconsin
JEFF SESSIONS, Alabama DIANNE FEINSTEIN, California
LINDSEY O. GRAHAM, South Carolina RUSSELL D. FEINGOLD, Wisconsin
LARRY E. CRAIG, Idaho CHARLES E. SCHUMER, New York
SAXBY CHAMBLISS, Georgia RICHARD J. DURBIN, Illinois
JOHN CORNYN, Texas JOHN EDWARDS, North Carolina
Bruce Artim, Chief Counsel and Staff Director
Bruce A. Cohen, Democratic Chief Counsel and Staff Director
------
Subcommittee on Terrorism, Technology and Homeland Security
JON KYL, Arizona, Chairman
ORRIN G. HATCH, Utah DIANNE FEINSTEIN, California
ARLEN SPECTER, Pennsylvania EDWARD M. KENNEDY, Massachusetts
MIKE DeWINE, Ohio JOSEPH R. BIDEN, Jr., Delaware
JEFF SESSIONS, Alabama HERBERT KOHL, Wisconsin
SAXBY CHAMBLISS, Georgia JOHN EDWARDS, North Carolina
Stephen Higgins, Majority Chief Counsel
David Hantman, Democratic Chief Counsel
C O N T E N T S
----------
STATEMENTS OF COMMITTEE MEMBERS
Page
Feinstein, Hon. Dianne, a U.S. Senator from the State of
California..................................................... 4
prepared statement........................................... 26
Kyl, Hon. Jon, a U.S. Senator from the State of Arizona.......... 1
prepared statement........................................... 34
Leahy, Hon. Patrick J., a U.S. Senator from the State of Vermont,
prepared statement............................................. 37
WITNESSES
Keim, Paul S., Regents Professor of Biology and Cowden Endowed
Chair in Microbiology, Northern Arizona University, Flagstaff,
Arizona........................................................ 4
Meislin, Harvey W., M.D., Professor and Chair, Department of
Emergency Medicine, University of Arizona Health Science
Center, Tucson, Arizona........................................ 6
Relman, David A., M.D., Associate Professor of Microbiology and
Immunology, and of Medicine, Stanford University, Palo Alto,
California..................................................... 8
Trent, Jeffrey, President and Scientific, Director, Translational
Genomics Research Institute, Phoenic, Arizona.................. 10
SUBMISSIONS FOR THE RECORD
Keim, Paul S., Regents Professor of Biology and Cowden Endowed
Chair in Microbiology, Northern Arizona University, Flagstaff,
Arizona, prepared statement.................................... 29
Meislin, Harvey W., M.D., Professor and Chair, Department of
Emergency Medicine, University of Arizona Health Science
Center, Tucson, Arizona, prepared statement.................... 38
Relman, David A., M.D., Associate Professor of Microbiology and
Immunology, and of Medicine, Stanford University, Palo Alto,
California, prepared statement................................. 50
Trent, Jeffrey, President and Scientific, Director, Translational
Genomics Research Institute, Phoenic, Arizona, prepared
statement...................................................... 56
RAPID BIO-TERRORISM DETECTION AND RESPONSE
----------
TUESDAY, MAY 11, 2004
United States Senate,
Subcommittee on Terrorism, Technology and Homeland
Security, Committee on the Judiciary,
Washington, D.C.
The Subcommittee met, pursuant to notice, at 9:35 a.m., in
room SD-226, Dirksen Senate Office Building, Hon. Jon Kyl,
Chairman of the Subcommittee, presiding.
Present: Senators Kyl and Feinstein.
OPENING STATEMENT OF HON. JON KYL, A U.S. SENATOR FROM THE
STATE OF ARIZONA
Chairman Kyl. This hearing of the Senate Subcommittee on
Terrorism, Technology, and Homeland Security of the Senate
Judiciary Committee will come to order. Let me announce at the
beginning that Senator Feinstein is expected to be here
momentarily, and hopefully we will have some other members of
the Subcommittee as well.
I think that most of the people here are aware that despite
the best-laid plans, one can't always plan and the hearing this
morning in the Armed Services Committee on the events in Iraq
recently has taken the TV crews and some of the other Senators
who otherwise would have been joining us here. Therefore, it
may deplete our ranks, but we will create a record which will
be shared with all of the members of the full Committee, as
well as the members of the Subcommittee.
I would also indicate that we will keep the record open for
questions that members of the panel might have, and would ask
that the witnesses, if possible, respond to those questions in
writing. We will keep the record open until 5:00 p.m. on
Tuesday, May 18.
I will begin with a brief opening statement, and then by
then perhaps Senator Feinstein will be here. At an appropriate
time, if she is not here, we will break for whatever opening
statement she or other members of the Subcommittee might have.
Earlier this year, this Subcommittee on Terrorism,
Technology, and Homeland Security examined ways to protect the
Nation from cyber attacks and from attacks against our
seaports. Today, we will examine a new method that would
improve our ability to detect and respond to a bioterrorism
attack.
In recent days, the media has noted the ever-evolving
threat of bioterrorism and the catastrophic consequences of a
successful large-scale bioterror attack. Earlier this year,
President Bush said, ``Armed with a single vial of a biological
agent, small groups of fanatics or failing states could gain
the power to threaten great nations, threaten world peace.
America and the entire civilized world will face this threat
for decades to come. We must confront the danger with open eyes
and unbending purpose.''
Well, one promising way to confront this danger is a
medically-based bio-attack detection and warning system which
could detect and monitor infections from biological attacks and
quickly communicate the results across the country.
[The prepared statement of Chairman Kyl appears as a
submission for the record.]
Good morning.
Senator Feinstein. Good morning.
Chairman Kyl. Health providers often cannot quickly
distinguish between infection caused by a bioterrorist attack
and infection caused by routine causes. They must rely on a
series of sequential, inefficient actions that delay a prompt
response.
In a bioterrorist attack, delayed diagnosis allows
contagion to spread. Health care providers need a way to
determine immediately whether a person has been exposed to a
bioterrorist agent or a naturally-occurring infection. One
possible solution is Project Zebra. Project Zebra was developed
by a consortium of some of the country's leading scientists and
industrial entities to establish a diagnostic test to enable
medical personnel to distinguish between infections caused by
bio-threat agents from those routinely found in patients.
I should note that it is called Project Zebra because
physicians in training are traditionally taught that the most
common diseases occur most commonly; that when you hear hoof
beats, think of horses, not zebras, is the medical terminology.
The dilemma in bio-defense is, of course, how to detect
that one zebra, the rare bio-weapons pathogen, amidst the
medically common germs that cause most infectious diseases.
Well, Project Zebra would improve the ability to detect and
respond to bioterrorist attacks. Early detection would mean
faster diagnosis, and faster diagnosis would save lives,
optimize the treatment selection, and enable the rapid triage
of at-risk populations, which would reassure the worried and
thereby reduce risk of panic.
The Subcommittee today will hear from four experts. First
is Dr. Paul Keim, who is the Director of Pathogen Genomics at
TGen and the Cowden Endowed Chair in Microbiology at Northern
Arizona University. He has been recognized as one of our top
microbiological researchers with his election to the American
Academy of Microbiology. During the 2001 anthrax letter
attacks, Dr. Keim served the country by diverting his
laboratory and personal efforts to the DNA analysis of the
anthrax strain from the letters, and his work resulted in one
of the most tangible forensics leads in the anthrax
investigation. Dr. Keim's laboratory has a database of 450
unique types of anthrax, based on the world's largest
collection of anthrax strains that exist anywhere in the world.
Dr. Harvey Meislin is the head of the University of Arizona
Department of Emergency Medicine and is a professor at the
University of Arizona College of Medicine. He is president of
the American Board of Medical Specialties and received his
bachelor of science degree in chemistry from Purdue and his
medical degree from Indiana University.
Dr. David Relman is associate professor of medicine and
microbiology and immunology at Stanford University School of
Medicine, and Chief of Infectious Diseases at the Veterans
Administration Palo Alto Health Care System in Palo Alto,
California. He has published over 140 peer-reviewed articles,
reviews, editorials and book chapters on pathogen discovery and
bacterial pathogenesis.
He received the Senior Scholar Award in Global Infectious
Diseases from the Ellison Medical Foundation in 2002 and the
Squibb Award from the Infectious Diseases Society of America in
2001. Dr. Relman received his bachelor of science degree in
biology from the Massachusetts Institute of Technology and his
medical degree from Harvard Medical School.
Finally, Dr. Jeffrey Trent is president and scientific
director of the recently formed Translational Genomics Research
Institute, or TGen, in Phoenix, Arizona. He was formerly the
scientific director of the National Human Genome Institute at
the National Institutes of Health, and also served as chief of
its Cancer Genetics Branch. Dr. Trent received his
undergraduate degree from Indiana University and his master's
of science and Ph.D. degrees in genetics from the University of
Arizona.
We have a distinguished panel of witnesses before us today
and I am interested in examining with them how to make the
Nation safer through a medically-based bio-attack detection and
warning system which could detect and monitor infections for
biological attacks and quickly communicate the results across
the country.
Rather than attempting at great cost to set up sensors
across the Nation, which many believe would not be feasible,
Project Zebra could quickly determine whether symptoms of
patients presenting themselves to emergency rooms were the
result of normal diseases or from biological agents.
In conclusion, the Secretary of Homeland Security, Tom
Ridge, recently said the potential catastrophic consequences
that the use of a biological weapon could have on our country
obviously makes it a critical, vital area of homeland security
concerns.
The Deputy Secretary of Defense recently said, and I am
quoting here, ``The American people must appreciate the
magnitude of the danger that we face from possible biological
terrorism. The threat is real. It is deadly serious. As
horrible as it was to have thousands of innocent Americans
killed on our own territory on that tragic day, that is nothing
compared to what terrorists could do with biological weapons
that we know they have been actively seeking. In many ways,
biological weapons may be ideally suited for the methods and
purposes of terrorists. A mass attack with anthrax or some
other biological agent could bring about civilian casualties
and catastrophic damage to our economy on a scale far beyond
even that which we experienced on September 11, as devastating
as that was.''
Well, these comments are chilling, but they drastically
point to the need for technology such as the one being
developed by Project Zebra that will help the Nation detect and
respond to a bioterrorism attack. I am very pleased to have the
witnesses before us today.
With that, let me turn to the co-chair of our Subcommittee,
Senator Dianne Feinstein.
STATEMENT OF HON. DIANNE FEINSTEIN, A U.S. SENATOR FROM THE
STATE OF CALIFORNIA
Senator Feinstein. Thanks very much, Mr. Chairman, and I
won't take very much time. I want to thank you for the hearing
and thank our witnesses. I will put my statement in the record,
if that is all right with you.
I remember our earlier hearings on bioterrorism, the fact
that we had about 36 deadly pathogens; that anthrax existed in
22,000 places in the United States; that we had a very lax
system with respect to the handling of these deadly pathogens,
if you recall, and some of our findings were placed in the
bioterrorism bill. What I am really interested in today is to
see whether Project Zebra would have applicability to all of
the deadly pathogens or just some of them, what the time line
is, and how deep and broad the project can take us in this
arena.
So I look forward to hearing the witnesses and I will put
my statement in the record.
[The prepared statement of Senator Feinstein appears as a
submission for the record.]
Chairman Kyl. Thank you. Those are great questions that I
hope we can get answered.
Let's go in this order from my right: Dr. Keim, and then
Dr. Meislin, Dr. Relman, and then Dr. Trent.
STATEMENT OF PAUL S. KEIM, REGENTS PROFESSOR OF BIOLOGY AND
COWDEN ENDOWED CHAIR IN MICROBIOLOGY, NORTHERN ARIZONA
UNIVERSITY, FLAGSTAFF, ARIZONA
Mr. Keim. Mr. Chairman and Senator Feinstein, thank you
very much for holding this hearing. It is very humbling to be
here in this great institution and we really greatly appreciate
your efforts for the defense of this country.
I have submitted an extensive written record, but in my
oral comments today I would like to revisit some of the
forensic analysis that I have performed over the last couple of
years on anthrax, in particular, and try to show how we can see
the threats coming out of this, as well as to see the promise
for diagnostics in the health care arena and the clinical
arena.
Unfortunately, bioterrorism is all too familiar to the U.S.
Senate. It has now become perhaps the most notorious bio-crime
ever committed in this country. Technology developed in my
laboratory has played a prominent role in this investigation.
But because it is an ongoing investigation and someday I hope
to actually be testifying at a criminal proceeding against the
perpetrator, I will be limited in what I can say about the
actual case in this particular forum.
However, I can tell you that the first victim of the
anthrax attack who died in Florida, in fact, died of a type of
anthrax that was commonly found in laboratories around this
country, and indeed around the world. This result was
accomplished by using highly precise DNA fingerprinting
technology developed in my laboratory.
In addition, we were able to determine the entire genetic
composition of this particular type of anthrax. So it was
proven beyond a doubt that the anthrax involved in this attack
was of a particular type. So, again, this is highly precise
diagnostic capability which at least now is only available in
the forensic arena.
Prior to 2001, this technology had been developed for other
uses. For example, we analyzed the military accident that
occurred in Sverdlosck, which was at that time part of the
Soviet Union. Sverdlosck is a city now known as Yekaterinburg
in the Ural Mountains. There was a production facility for
anthrax spores that the Soviets maintained there called
Compound 19.
Some time in 1979, they released a cloud of spores that
wafted off across the civilian population that was adjacent to
this facility. We don't know how or why this occurred, but we
do know that over 60 people died in this accident. Physicians,
pathologists in particular, were able to smuggle out portions
of these people's necropsy samples which we analyzed and were
able to demonstrate that, in fact, that cloud of spores was a
mixture of anthrax types. Exactly how or why they were doing
this isn't clear, but again the precision of genomic analysis
allowed us to figure this out.
In 1993, the doomsday cult Aum Shinrikyo released a spray
of anthrax across a suburb, Kameido, a suburb of Tokyo. If you
look closely here, you can actually see a cloud of anthrax
wafting out. Tokyo being one of the densest populated regions
of the world, of course, was very susceptible to this type of
attack. In spite of this, though, no one died.
Our analysis of the spores that were in this cloud later
revealed the reason why this attack had failed and it had to do
with the type of anthrax that the Aum Shinrikyo cult was using.
In fact, they were using a vaccine strain that was non-lethal,
and so their efforts to carry out this biological attack failed
for that reason. Again, an example of our ability to precisely
identify using forensic techniques.
Now, the Aum Shinrikyo doomsday cult has really set up a
paradigm or a model for all sorts of terrorists around the
world. We know that the Aum Shinrikyo were interested in
chemical attacks. They carried out the sarin gas attack two
years later in the Tokyo subway.
In addition to this anthrax attack, they have carried out
several other biological attacks. And while they were a long
way from creating a nuclear weapon, they were very interested
in radiological and nuclear devices to carry out their
terrorism.
We can't really predict what the next bioterrorism or
terrorist event will be because there are so many different
possibilities. But one thing we can be sure of is that they
will, in fact, be trying to harm American citizens, impacting
their health. My esteemed colleagues will, in fact, cover
chemical, biological and radiological challenges, and the
diagnostic capabilities that we hope to employ to help counter
this problem.
Finally, I would just like to summarize by saying our
studies of bacterial genomes has led to these highly precise
methods that have been used for forensic analysis. These same
types of methods are very applicable for many different
pathogens. As you mentioned, there are many, many different
types of germs, viruses and bacteria that can be used in
biological attacks.
These same approaches are either available or very close to
being available for all of them and could, in fact, move from
the forensic arena, where we have put a great deal of effort in
the last two years, into the clinical arena without all that
much trouble.
So with that, I would yield the floor to my esteemed
colleagues' testimony and I would be glad to answer any
questions.
[The prepared statement of Mr. Keim appears as a submission
for the record.]
Chairman Kyl. Thank you, Dr. Keim.
Dr. Meislin.
STATEMENT OF HARVEY W. MEISLIN, PROFESSOR AND CHAIR, DEPARTMENT
OF EMERGENCY MEDICINE, UNIVERSITY OF ARIZONA HEALTH SCIENCE
CENTER, TUCSON, ARIZONA
Dr. Meislin. Good morning, Senator Kyl, Senator Feinstein.
Thank you for the opportunity to appear before you and discuss
the challenges facing our medical system in light of the
potential for terrorist attacks.
My name is Harvey Meislin. I am chairman of the Department
of Emergency Medicine at the University of Arizona Health
Science Center. I also have the privilege of being the
president of the American Board of Medical Specialties, the
organization that represents all 24 medical specialty boards in
the United States.
Today in the United States, the first physician point of
care for acute medical injuries and illnesses 24/7 is the local
ER. ER care has become an essential community service,
providing front-line health care for acute trauma, medical
illnesses, local disasters, and even terrorist attacks.
The ER safety net not only delivers medical care, but
coordinates disaster planning, emergency medical services,
poisoning and infectious disease management and public health
surveillance. ERs across the country, however, are in crisis
and our safety net is collapsing. Today, about one in every
three U.S. citizens receives care in an emergency department
annually--over 114 million visits. About 10 percent of our
population accesses the 911 system and takes an ambulance ride
every year.
In spite of this, over the last decade we have seen the
closing of over 1,100 emergency departments in the country. ERs
today are overcrowded, understaffed, have almost no surge
capacity to handle mass casualties, yet still remain the front-
line medical safety net for communities throughout this
country.
The staff in emergency departments lacks the diagnostic
tools, the education and the therapeutic resources to care for
victims of a terrorist attack. Emergency physicians and nurses
have existing training requirements that already strain the
system, but contain almost nothing regarding chemical, biologic
or radiologic attacks.
I can tell you that most physicians charged with caring for
the acutely ill and injured in our country had little knowledge
about the diagnosis and the management of anthrax before the
fall of 2001. Likewise, physicians knew almost nothing about
sarin and nerve gases prior to the Tokyo subway attack of 1995.
And the knowledge gained from these isolated events is fading,
as most physicians feel they will never have to care for
patients exposed to these toxic materials.
Importantly, and why we are here today, there is a
disconnect between what is happening at the basic science
research level and the application of this new knowledge to the
front lines of medical care. The gap between scientific
discovery and what is applied at the bedside widens everyday.
As you will hear from my colleagues, techniques and skills
that are currently being investigated at the basic research
level have the ability to identify normal versus abnormal
pathogens based upon either their genomic expression or the
human response to these pathogens. Yet, few of these
innovations have made their way to the front lines of medical
care in the ERs or the pre-hospital care system, where critical
life-and-death decisions are made every single day.
Medical aspects of an effective bio-defense system require
education, prevention and intervention. In the area of
education, just as we have trained our Nation's communities to
respond to cardiac events through the American Heart
Association's advanced cardiac life support course, and trauma
events from the American College of Surgeons' advanced trauma
life support course, we need to do the same to provide
practitioners with the knowledge and skills to manage victims
exposed to hazardous materials and toxic terrorism events.
The advantage of having one interdisciplinary program
focusing on the medical management of such patients is that it
has use in situations that occur in every community, every day
during peace time, while preparing medical professionals for
toxic terrorism and bioterrorism events.
We should promote a standard interdisciplinary program such
as the Advanced Hazmat Life Support program sponsored by the
American Academy of Clinical Toxicology and the Arizona
Emergency Medicine Research Center that are specifically
designed to teach physicians, nurses and other medical
personnel in the medical management of patients exposed to
hazardous material events, including toxic terrorism.
In the area of early alert and warning, we should create an
emergency room surveillance system. We need to know what others
are experiencing and keep a surveillance database both as an
intervention and prevention strategy. Local, regional and
national information should be shared to aid not only in
diagnosis and treatment, but in other areas such as quarantine,
public health, patient privacy and crowd control. Telemedicine
capabilities across the Nation would enhance medical care on
the front lines, especially in our rural areas.
In the area of rapid medical diagnosis and treatment, we
need rapid, high-performance diagnosis devices throughout all
major communities and risk-prone areas. Research is needed to
quickly and accurately identify pathogens at the bedside. In
the event of a bioattack, we cannot wait two or three days for
a culture result to come back. We need diagnostic tools that
rapidly and accurately identify natural and weaponized
biopathogens.
Clinicians on the front line of medicine and in our local
ERs must work closely with the researchers who are on the
cutting edge of science and who can identify the genomic
expression of a toxin and the body's response to such poison.
Likewise, these researchers need to work with the clinicians,
especially in an environment as complex as an emergency room.
Diagnostic devices need to be simple to the user and
specific to the pathogen. These devices must be able to
identify a broad array of offending pathogens--viruses,
bacterial, funguses--and differentiate the routine from the
rare and alert us when pathogens are weaponized.
In summary, today the front lines of medicine simply are
not prepared to diagnose and respond to a common virus while
concurrently ruling out a bioterrorist event or an emerging but
potentially lethal pathogen. Another vulnerability of our
system is the very uniqueness of the events under
consideration. We all hope that a bioterrorist attack will
never happen. Yet, in some ways the very fact that it is rare
makes its successful implementation more likely.
Today, we train individuals after an event occurs, and by
the time that information is needed again, the training is
stale and personnel often have moved on. Tomorrow, we can truly
obtain a war dividend. The same tools, training and reporting
systems that can be developed to diagnose the pathogen have the
capability to improve the care of patients everyday, in every
hospital, and in every medical office throughout the country.
They can reduce patient costs, as well as time away from work
and school.
Of even more importance, everyday use of such tools and
reporting assures that when the unexpected does occur, the same
tools and the same procedures will be available because they
have become routine and of proven value to individuals in the
health care system.
As you will hear from my colleagues, the science and
technology necessary to accomplish this goals is within our
grasp. This is not just an academic exercise. We can develop
these tools and achieve a level of practicality that will be
valued everyday by the individuals treated in the health care
system.
Mr. Chairman, I thank you for allowing me the privilege to
participate in this important hearing. I hope you will be able
to develop a process whereby researchers and clinicians will
work together to develop educational programs, medical devices
and diagnostic tools that will help the citizens in our country
in our war on terror as well as in everyday life.
Thank you.
[The prepared statement of Dr. Meislin appears as a
submission for the record.]
Chairman Kyl. Thank you, Dr. Meislin.
Dr. Relman.
STATEMENT OF DAVID A. RELMAN, ASSOCIATE PROFESSOR OF
MICROBIOLOGY AND IMMUNOLOGY, AND OF MEDICINE, STANFORD
UNIVERSITY, PALO ALTO, CALIFORNIA
Dr. Relman. Good morning, Chairman Kyl and Senator
Feinstein. Thank you for providing me and others at this table
the opportunity to address you on a new and rapidly developing
area of science that may revolutionize the way we can detect
and manage diseases caused by emerging and unanticipated
infectious agents.
I am an infectious disease clinician and a researcher at
Stanford University whose interests are in the discovery of
novel disease-causing agents and the methods that we need for
that purpose. I am also a member of the board of directors of
the Infectious Diseases Society of America.
In the late 19th century, we first acquired the ability to
detect and identify disease-causing bacteria. It is now 100
years later and we have a surprising inability to recognize and
diagnose infectious diseases. More than half of all patients
who have an infectious disease remain poorly or undiagnosed at
the time they come to medical care.
There are many reasons for this unsatisfactory state of
affairs and we can discuss those later, if you wish. But
suffice it to say that the consequences for this poor
capability in the diagnosis of infectious diseases are
profound. We are faced as clinicians with the unfortunate need
to use antibiotics in an empiric manner without an accurate
diagnosis. The consequence of this action is to promote the
development and spread of antibiotic-resistant bacteria, as
well as provide sub-optimal care for patients.
The best clinicians are known for their ability to listen
carefully to the patient and extract useful clues. We now have
a means for listening more carefully to patients than we have
ever been able to do with the use of certain kinds of
technology and insight that we have gained. This insight has
been made possible by the deciphering of the human genome
sequence.
One of the tools that has arisen from the human genome
project effort is a tool that I show you here called the DNA
chip or DNA microarray. On these arrays, there are many spots,
each of which corresponds in some cases to each of our
different 30,000 human genes.
Surprisingly, it turns out that our human genome and our
genes are not static entities; they are actually alive and
dynamic. And by that I mean they have the means to respond to
environmental stimuli. Different stimuli promote different
responses among these different genes and we can monitor that
activity, that response, on a device like this.
The challenge, therefore, is to learn how to read these
patterns in order to recognize what the stimulus was that
provoked this particular kind of profile. This kind of analysis
has begun already and is most well developed in the area of
cancer, as you will hear from Dr. Trent.
In the area of human gene expression profiling for
infectious diseases, the process is still in its infancy, but
the results appear to be encouraging. It appears that we can
glean from these patterns previously unrecognized features of
different individuals both in states of health and in states of
disease, such as infectious disease. In fact, we can sometimes
glean features that had not been recognizable among a group of
otherwise homogeneous humans. So you can see here a computer
has divided a group of individuals into two classes based upon
features that hadn't been recognized prior.
What is needed at this point? First of all, we need a much
more extensive set of data from many different kinds of
infection, naturally-occurring infection, so that we can
recognize different untoward events one from another in
different individuals over time. The promise is that this
approach will allow us to recognize disease at the earliest
possible moment, even before an individual is aware that an
untoward event has taken place.
In addition, we need standardized methods and tools. We
need automated methods and miniaturized devices that might
bring down the cost of this technology and make it much more
affordable to implement across the board in the health care
delivery system.
The future looks quite promising, but the challenges are
quite large. The promise is that, as I say, we will be able to
recognize infection at the earliest possible moment when we can
distinguish the so-called worried well from the truly sick and
allocate in appropriate fashion what might be scarce resources.
The potential coverage across the threat space for this
kind of device is immense and could cover all of the different
kinds of both naturally-occurring and deliberately-released
agents that one can imagine. In the future, we might also
imagine that individuals might be monitored on a daily basis
for their state of health so that we can recognize these events
at an early point in time.
In conclusion, we stand on the verge of acquiring novel
capabilities. These capabilities have been brought about by
technology and science that has only recently come into play.
These developments need to be brought to the hands of the
clinicians who have an immense challenge in front of them. We
think we know how to approach this challenge today, but a great
deal more work is going to be necessary both to answer
unanswered questions as well as to promote maturation of this
technology.
I would be pleased to answer any questions.
[The prepared statement of Dr. Relman appears as a
submission for the record.]
Chairman Kyl. Thank you, Dr. Relman.
Dr. Trent.
STATEMENT OF JEFFREY TRENT, PRESIDENT AND SCIENTIFIC DIRECTOR,
TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, PHOENIX, ARIZONA
Mr. Trent. Thank you very much, Chairman Kyl and Senator
Feinstein. My name is Jeff Trent. I am the president and
scientific director of TGen, in Phoenix, Arizona. Prior to my
move to Arizona 18 months ago, I served for a decade as the
scientific director of the National Human Genome Research
Institute at the National Institutes of Health in Bethesda. I
really am delighted to have the opportunity to speak with you
today.
You have heard about dangers posed by biological outbreaks
and the fact that modern technology, including the technology
you just heard about from Dr. Relman, could be part of a
process toward addressing shortcomings in early detection and
treatment capabilities. I would like to discuss very briefly
two other elements for your consideration.
The first is the critical need for supporting
competitively-reviewed approaches to implement comprehensive
and effective end-to-end solutions. The second is to provide
you with just very brief information about collaborative work
that is beginning to suggest that the activities of genes, the
living nature of genes that Dr. Relman just mentioned, may, in
fact, help serve as a bio marker for radiation exposure in the
same way that they are also useful in being a monitor of
exposure to pathogens.
While our focus must appropriately be on biological attacks
that threaten our safety, the fears of possible dirty bomb
detonation or similar situations have clearly spurred interest
in the research community nationally and internationally in the
search for bio markers that could, in fact, be useful for
rapidly assessing radiation exposure and large potentially
exposed populations.
So for nearly 20 years, I have worked to create and utilize
tools and techniques that identify these genetic signatures for
diseases, as mentioned, such as breast cancer and leukemia and
melanoma and others. But while at the NIH, I also had the
opportunity to work on killer viruses such as HIV, HTLV, and
with investigators at Fort Detrick on the Ebola virus as well.
But it is important for this Subcommittee to be aware of
similar progress, albeit preliminary, that is beginning to give
us hope that radiation-associated gene response signatures
could, in fact, be incorporated into a biomonitoring approach
similar to that just described for bio-threat agents.
My first slide just shows an example, as Dr. Relman showed
you. In this case, the stimulus is radiation, and using gamma
radiation similar to that that is found in x-rays and in work
that has been done in concert with investigators at the
National Cancer Institute headed by Dr. Al Fornace, we have
begun to look at very low doses of radiation and to look for
consistent sets of genes that may be modified in response to
radiation exposure.
If one could identify a set of genes by such techniques,
one could incorporate these into the aforementioned rapid
assays that would utilize nano technology, protein and gene
expression analysis, perhaps be utilized again on easily
biopsied tissue like blood, and which could become part of a
profile that could be an indicator not just of exposure, but
perhaps absolute dose of radiation as well.
The next slide that I have just gives you examples of
preliminary information using very low doses of radiation, and
the point is really just to, as Dr. Relman mentioned, begin to
put in place a feeling that we need to sort this information.
What this slide really tries to depict is that if one looks at
even low doses of radiation--in this case, we were looking at
radiation in the area of 0.2 Gray, a measurement tool for
looking at radiation response.
The experience of the military that is the triage point
looking to detect for 0.2 Gray or above, to give you just a
feeling, a single chest x-ray would give you approximately one-
ten thousandth of a Gray, or 0.0001 Gray. An upper GI, if you
have had a barium enema, gives you about 0.1 percent. So what
we have begun looking at is low-dose exposure, moving it up to
the higher dose to be able to look at consistent changes that
could be useful in this type of setting.
We have also join forces with the investigators at the DOD-
funded National Functional Genomics Center at the H. Lee
Moffitt Cancer Center in Tampa, Florida, to investigate protein
markers for being able to look at this. Here, these
investigators are looking at cancer patients being treated with
radiation to oblate their bone marrow for bone marrow
transplant. We are looking at those cases to be able to look at
radiation response moving forward as well.
The point is just that we may be able to utilize diagnostic
testing to identify, in addition to bio-threat, radiation-
associated genetic signatures. I remain convinced that the most
important thing I can emphasize today is the need for
competitively-selected end-to-end solutions that do push
forward this early detection focusing on the reality that early
detection will be a key to saving lives, optimizing treatment,
triaging at-risk populations--again, the worried well that you
have heard about--and being able to help in many regards, and
that this would include identification of these molecular
signatures, diagnostic platforms, decision support systems and
information architecture.
So I thank you very much for the ability to be able to put
forth at least as one part of a solution the mobilization of
incident activity that could be utilized in a national
stockpile, as well as for a key piece in early detection.
Thank you.
[The prepared statement of Mr. Trent appears as a
submission for the record.]
Chairman Kyl. Thank you, Dr. Trent.
Senator Feinstein may have to attend another hearing which
is already underway. Therefore, I am going to ask her to ask
the first set of questions and then I will follow that.
Senator Feinstein.
Senator Feinstein. Thanks very much, Mr. Chairman. Thank
you all very, very much for your testimony.
I wanted to ask you a question about Project Zebra. I have
a difficult time understanding it because assuming you have
these 36-or-so deadly pathogens, and assuming that once these
pathogens hit someone the likelihood is that they will die, and
assuming that once one hits they hit any number--hundreds,
thousands, tens of thousands--of people to be effective, I
don't understand how a clinical response in terms of a clinical
diagnosis is very helpful because it seems to me it is too
late.
It seems to me that the sniffer technique of trying to
detect the chemical before it emerges, if you can--and that may
not be possible either--is the most realistic in terms of being
able to evacuate an area and actually save lives.
Could you comment, please?
Mr. Keim. Perhaps one of the clinicians should respond
first and then I will follow.
Senator Feinstein. This is directed toward Project Zebra,
whoever is the advocate for that.
Dr. Relman. I would be happy to provide a short response,
Senator Feinstein. We, I think, would propose that this generic
kind of effort be seen as a complement to other efforts, as
well. But it remains true that for a number of these threat
agents, if one were able to detect exposure at an early time it
might be possible to intervene and save lives with certain
kinds of therapies and preventative measures.
Senator Feinstein. For all of the deadly pathogens? I mean,
anthrax, yes, but others?
Dr. Relman. We believe that for at least a good number of
others, there either are now or will be some means of
intervening. That is our hope.
Senator Feinstein. How many others and which others?
Dr. Relman. Currently, I would say it is about half we have
something we can do for now. The other aspect of this is that
whether or not we can save all those who have been exposed, we
could certainly at the same time distinguish those who have
been exposed from those who haven't and direct these limited
resources toward an attempt to help and ameliorate disease in
the small number that have actually been exposed.
Senator Feinstein. I would like to ask this question. For
those of you who work with deadly pathogens, have you noticed a
change in the procedures for handling those pathogens, a
tightening up, and if so, what are they?
Mr. Keim. I am probably the best qualified to answer that
question.
Senator Feinstein. Senator Kyl mentioned that you have
large amounts of anthrax.
Mr. Keim. Let me say right from the beginning that, in
fact, we have very good security before September 11. But after
September 11, we voluntarily increased our security
tremendously. And, again, I won't go into details about that
security in this forum, but I can tell you that we increased
our security perhaps five-fold.
Senator Feinstein. Have you heard from the Department of
Health and Human Services?
Mr. Keim. Definitely. People who work in this field live in
our backyard now, and so I would say that at least in my
personal experience the Centers for Disease Control, the
Department of Agriculture and the Department of Transportation
have stepped up their monitoring. Certainly, they have required
compliance. And it has been, again, my experience that the
laboratories have again voluntarily complied and met these
standards.
Senator Feinstein. Just one point. The Department of Health
and Human Services on March 25 presented what is called a
summary report on select agent security at universities, and
let me just quote it. ``In general, our reports disclose
serious weaknesses that compromise the security of select
agents at all universities we reviewed. Physical security
weaknesses at all 11 universities left select agents vulnerable
to theft or loss, thus elevating the risk of public exposure,''
and it goes on.
Mr. Keim. I am familiar with that report. I will assure you
that one of those eleven was not in Arizona. That was
disheartening, actually, to hear that report. Our personal
experience is, and the reaction of the inspectors who have
visited our laboratory have agreed that we, in fact, have
excellent security.
Senator Feinstein. I am really concerned about this because
it was brought to my attention. Someone walked into a
university, took a letterhead, went and filled it out, sent it
to a mail order house and bought plague. That kind of thing has
to stop, and we thought that by really activating HHS to move
in and set the rules and regulations for the position, for the
transfer and for the movement of these pathogens that we
wouldn't have a report like this. So it is very disappointing
to me.
Did somebody else want to comment? Yes, Dr. Relman.
Dr. Relman. I would just add that I think we all share your
concern equally. We can tell you that the level of sensitivity
within the academic community has risen immensely. We all now
live and breathe this kind of concern, and I think it is only
with that kind of sensitivity that we will be able to recognize
perhaps those among us or those who seek to collaborate with us
that aim to do harm.
One other brief comment. I have been involved in work with
the CDC on the use of smallpox virus in monkeys at CDC and I
can tell you that the security there and the sensitivity to
security surrounding that particular agent is now quite
overwhelming and quite impressive.
Senator Feinstein. I guess that is it for me, Mr. Chairman.
Thank you very much.
Chairman Kyl. Okay, thank you, Senator Feinstein.
Let me get right to the heart of one of the points Senator
Feinstein had raised earlier, both the breadth of the potential
here for detection of pathogens and also the time within which
this might be accomplished. I think at least one of you talked
about the breadth being almost pervasive.
The question is how close would we be to developing a
technique by which this could actually be implemented. I know
that may depend to some extent on how much support there is in
the community generally and perhaps with NIH, and so on. But
can you give us some idea of how soon this might be expected to
evolve?
Mr. Keim. There are different degrees of implementation, of
course, and it is my belief that devices that could, in fact,
be monitoring the host response could be available within a
couple of years. How discerning they will be we don't know at
this point, but I think that a device that provides the best
available science to clinicians needs to be developed and put
into the clinical setting so that as the science becomes
better, we can adapt those devices to provide whatever the best
science is.
Again, that means that we have to be able to have people
working on the devices. We have to have people working on the
science, the host response, as well as getting clinicians
engaged with the basic scientists in a fashion that is going to
make it effective.
Our hope and what we believe will happen down the road is
very grand, but we need to start modestly and get something in
place so that we can start to build upon that. And, again, a
device that can deliver the best science that is available is
what we need to be striving for.
Chairman Kyl. Now, Dr. Relman, you testified that perhaps
on the order of about half of the pathogens out there we could
deal with, if we detected them early enough, in a way that may
help patients if we could prioritize our treatment.
So part of this, as I understand it, is to differentiate
and appreciate that we don't have to deal with everybody that
presents themselves to an emergency room to identify those that
really specifically do need care and then focus our treatment
on them; that that would maximize our ability to respond to a
crisis.
One of the ways that we are trying to do this already is
through something called Bioshield, which is to create
stockpiles of certain kinds of medicines to deal with outbreaks
or potentially a bio-terror attack, and I gather to not only
develop those but also to have them stockpiled for response.
In what way would the kind of detection techniques that you
are talking about here enhance the ability to prioritize and to
develop treatments that could be quickly available anyplace in
the country?
Let me ask it another way. I am presuming that it wouldn't
be possible to have every single antidote or treatment for
every single potential pathogen in every emergency room in the
country; that there has got to be some regionalization and
quick response to get the material to the right place, or else
it would simply be cost-prohibitive.
How would the kind of work that you are talking about here
this morning enable us to better do that prioritization and
therefore have a reasonable way of dealing with a potential
attack rather than simply having to have everything in every
location?
Dr. Meislin.
Dr. Meislin. Senator, I think you need to look at these
pathogens as a myriad of things. Some are very quick. Nerve
gases are quick; they are a matter of minutes to hours. Bio-
pathogens often are a matter of hours to days, and then there
are others such as radiologic effects which are months to
years.
I think if you want to prioritize, you really need to look
at the life-and-death threats of pathogens. You also have to
realize that many times the presentations of these are not
unique. Headache, sore throat, stiff neck, ill feelings are
common every single day in every single emergency department.
How would one physician differentiate the walking wounded from
the severely attacked? We need to have those skills.
The diagnostic devices have the ability to give us the day-
to-day information. Is this a virus, is this a bacteria, is
this a bad one, is this the routine one, versus are you
exposed, is this a pathogen? You relate that to the
stockpiling. You have to know what it is you are treating, what
the speed of it is and then get the antidotes and get
medication. So it is a whole process.
The reality of just having stockpiling will only serve you
well if you know what you are dealing with and you know the
numbers you are dealing with, and you are kind of dealing with
the end result, not the front end of it. At least my premise
here is that we need to know the front end. We need from the
presentation either as a community health disaster or as
individual by individual what is going on. We need the
diagnostic tools. They have the ability for routine care, they
have the ability in the event of a bioterrorist attack.
Chairman Kyl. And you said in your testimony that we can't
wait two or three days in the case of a bio-attack. What is the
prospect, then, for having a diagnostic capability in every
emergency room in the country so that we wouldn't be waiting
two or three days for the lab results to come back?
Dr. Meislin. I believe you heard from Dr. Keim, Dr. Trent
and Dr. Relman here that we have technology and research that
is probably a few years away. I think once there is a device,
the device can be anywhere. I think the device can be
miniaturized, that devices can be able to put either in
communities or in local emergency departments, if indeed they
are specific enough to work.
I don't think the issue of having it in every emergency
department is a problem. Every emergency department has
diagnostic tools, laboratories, x-rays. We have all of these
devices now. If there is such a diagnostic tool that can be
developed and implemented, I don't think the problem is getting
it to local emergency departments. I believe the problem is
really getting a device that has the sensitivity and the
specificity to tell us what we need to know.
Chairman Kyl. Does anybody else want to comment on that?
Dr. Trent.
Dr. Trent. I echo your earlier comment that one of the ways
that this will permeate the infrastructure and be able to
participate in the incident management is for the Government to
aggressively champion this as indeed one of the important
elements, as Dr. Relman mentioned, of a comprehensive approach
that includes, of course, fixed-point sensoring, but also
recognizes that history tells us that in the case of bio-threat
agents such as the ones Dr. Keim mentioned, it may not be
possible to detect in every feasible instance every example of
attack and that there could be the presentation of sick and
dying people that we have to deal with and we have to triage.
But I would also agree that there is a pre-symptomatic
value to these types of aspects as well; that this is part of
the important component for developing tools that would perhaps
give us that canary-in-the-coal-mine sentinel approach for
being able to look at that. And Dr. Relman's work, I think, is
an example of that and trying to recognize that the harboring
of some of these signatures can be maintained in our biologic
system and can be recognized over time.
Chairman Kyl. One of the things that I think would help the
Congress direct resources would be a better appreciation of the
potential for an attack of this kind. If it is a very rare or a
longshot kind of thing, then that might give us time, we would
think. But if it is much more likely that terrorists are
actually working on these kinds of agents, then that might
cause us to accelerate our efforts.
Dr. Keim, let me ask you in a general way--I don't want to
get into anything classified here, but in a general way do you
have any experience that suggests that terrorists are indeed
working on, in your case, different strains of anthrax that
could be used? Put that into perspective for us.
Mr. Keim. I think the best way to put it in perspective is
to look at what has happened historically. We have had
biological attacks in this country before the September-October
2001. There was a bioterrorism attack in Oregon by a radical
cult. There have been disgruntled workers who have poisoned
their coworkers. Indeed, we probably experience what I would
call bio-crimes almost on a weekly basis in this country
involving intentional infection by HIV.
So it isn't like it hasn't happened. It has been very
present. Unfortunately, the anthrax letters show how effective
it can be, and so I think that there is no doubt that this is
going to happen again. Putting a probability or a date on it
would be impossible.
It is important, I think, to follow up with what Dr.
Meislin mentioned that time is of essence here, and also that
the personnel that are involved in doing this have to be doing
it on a regular basis. In the case of a medical diagnostic
device, this will offer such a dividend to physicians and to
health care that it will be used and utilized on a daily,
hourly, probably moment-by-moment basis in emergency rooms and
in clinics across the country. Physicians will know how to use
it. If we can engineer a value-added or a war dividend into
these devices at the same time that we are monitoring for these
exotic diseases like anthrax, it will be used and it will be
ready to go when the event occurs.
Chairman Kyl. Dr. Relman.
Dr. Relman. I would just add a few comments in support or
what Dr. Keim has just said. In December of this past year, Dr.
Ben Pietro from the Defense Intelligence Agency and I published
a paper in the journal Science describing and providing direct
evidence that Al Qaeda has, in fact, been interested in trying
to acquire B. anthracis, a virulent anthrax bacteria, as well
as other agents. This is public information and further
documents associated with this article are available through
the Freedom of Information Act. So I would be happy to make
that available to you and others as you see fit.
But I think you would have to say that if you were a
betting person, the most likely event we face in the near
future of a major probable impact is avian flu, and what we are
talking about today would be equally useful to the clinician
trying to sort avian flu from those with many other
identically-appearing infectious and non-infectious problems.
Chairman Kyl. And just for the uninitiated here, what is so
bad about avian flu?
Dr. Relman. Avian flu is a new variant of influenza that
has already emerged into the animal populations of Southeast
Asia and may, in fact, represent the next world pandemic,
worldwide epidemic, of flu to hit human beings on the scale of
1918, so a potentially catastrophic event.
Chairman Kyl. In other words, it can kill you?
Dr. Relman. This kills about two-thirds of the humans it
has infected so far. It has simply failed to acquire the
ability to transmit from person to person easily, but everyone
believes it will acquire that ability quite soon.
Chairman Kyl. So having this kind of diagnostic capability
would be important for both naturally-occurring as well as man-
inducted pathogens?
Dr. Relman. Absolutely.
Chairman Kyl. One of the questions deals with this
complementary relationship between sensors and this kind of
diagnostic technique. I would like to have any of you who could
discuss that in a little bit more detail. I think there is a
sense that sensors might be an efficient way to test in a
particular confined area at a particular point, maybe not so
much all over the United States. But also could you comment on
what the technology is with respect to what it could sense and
how important that is, versus the kind of technique that you
are talking about here?
Dr. Keim.
Mr. Keim. I think the point that we made before that these
are not mutually exclusive technologies is very important.
Decisions that will have to be made by the U.S. Government and
public health officials will be how much coverage do you want
and you are willing to pay for when it comes to environmental
detectors. Do you want to just protect large events in
Washington, D.C., and major cities? Are you going to try to
protect the western plains of Kansas, the Sonoran Desert? I
think the answer is no to many of those questions, because the
price tag will be exorbitant.
The one thing we do know is that when people get sick, they
show up in emergency rooms and that type of diagnostic
technology will be complementary and will be used on a regular
basis. If there is an event or if there is not an event, it
will be helping out this country.
Chairman Kyl. Yes, Dr. Relman.
Dr. Relman. The other thing to add is that we now know from
the routine use of these environmental detectors that there are
occasional positives during times when we don't believe we are
under deliberate attack. One of the complementary advantages
and values of a human diagnostic chip is its ability to help us
interpret the results of the biosensors.
You detect an anthrax spore in a room here in the Senate
office building and the human response element can tell you
whether, in fact, there are any humans here who are telling you
that they have been exposed to something serious and untoward
and are about to become ill.
Chairman Kyl. Dr. Meislin.
Dr. Meislin. Sensors have the ability to detect the
environment, or devices. Take it down to the individual. Again,
let me take it into my world. It is three in the morning, and I
gave you an example in my testimony, but a young college
student who has just returned home from Hong Kong on an
educational experience comes into the emergency department with
some headache and neck stiffness and a little bit of fever and
some nausea and some vomiting.
The physician there says, well, it looks like meningitis.
Typically, today, there is a viral meningitis and there is a
bacterial meningitis. But you know SARS is coming back this
year into Hong Kong and maybe it is something there, and
perhaps the environmental monitoring detected something in the
air. Something was going on. Maybe it is the evolution of the
avian virus coming in here.
So what is a clinician to do at three in the morning? Do I
quarantine the individual? Do I quarantine her dormitory? Do I
put her in isolation? Do I do what we call the shotgun
approach? I treat her with anti-virals, I treat her with
vaccines, I treat her with antibiotics. I don't know what is
going on. I isolate her, with a cost probably in the hundreds
of thousands of dollars and thousands of man-hours and
disruptions of everybody, versus a device that can say, well,
she probably has hoof beats, not zebras, because we have the
ability to test what is going on at the human level, at the
individual level, and I can take a specimen from a bodily fluid
and I can test it and I can say it looks like it is the normal.
Perhaps the end result of this case is I treat her and I
send her home in a couple of hours, and her hospital bill is a
couple hundred dollars instead of a couple of hundred thousand
dollars and we don't have to worry about a community crisis. So
I think you need to take the environmental sensors from kind of
a 3,000-foot down to the device which is at the local emergency
department treating the human beings that are coming in day in
and day out with potential exposures.
Chairman Kyl. Let me ask Dr. Trent, in point of fact if you
have sensors at, let's say, something like the Super Bowl and
it detects something, obviously you still have to figure out
who has been infected and exactly what it is that they have
been infected with in order to know how to treat them.
So how does the sensor help with that latter point, and
isn't therefore this kind of what we mean by the complementary
nature of these two things--and in view of the fact that there
is very little time, a point that a couple of you have made, in
the case of some of these agents, obviously you want to get to
it as quickly as you can. How would something like Project
Zebra assist in that element of this?
Mr. Trent. Well, I think again the triaging of what we
continue to say is the worried well or those that may have been
exposed but are yet pre-symptomatic is an area in which we have
great hope, but again, as Dr. Relman mentioned, little data.
But without any question, as I mentioned, whether it is
radiation exposure or work from Dr. Relman and others in terms
of pathogen exposure, there are early signatures from the host,
from an easily biopsied tissue like blood that could at least,
we believe, be part of a triaging process for those that are
pre-symptomatic.
There are going to have to be areas put in place to triage
individuals so that if a sensor does come up, as you said, with
exposure at a mass event, how one triages that within the
normal community setting of the emergency room is very
difficult. One could imagine that this type of approach could
at least be one measurement tool that would be useful in the
armamentarium that the physician would use in concert with
their own good judgment and the other abilities they have to
make these assessments.
Chairman Kyl. So let me just hypothesize for a minute. Dr.
Keim, you talked about some different kinds of anthrax strains,
some of which were really dangerous and some of which were not
that dangerous. So you have got a sensor at, let's say, the
Super Bowl and it picks up the fact that there is something in
the air and maybe it is sophisticated enough to say it looks
like anthrax. I am not sure that they are that sophisticated or
not, but let's say they are.
Now, to have any effect at all, the news immediately has to
go out to everybody in, let's say, the Phoenix area, where we
are going to have a Super Bowl in a couple of years, that
sensors have just detected something really bad in the air.
What is the likely effect on all of the emergency rooms in the
entire three-million population area around Phoenix, and what
happens if you don't have the kind of capability we are talking
about here?
You have got the sensors and everybody worries that they
have been infected, obviously, because you don't have any idea
how far it has spread. You can't withhold the information. The
whole point of the sensors is to let people know that they had
better see whether there is something wrong with them.
Everybody that has got a sniffle is going to be panicked to
death, and even those who don't are going to worry. So now you
have got three million people trying to get into an emergency
room.
What is the advantage of having the kind of thing we are
talking about here, over what physicians currently do to try to
differentiate and diagnose and triage?
Dr. Meislin. Senator, I am sure you probably know the
condition of the emergency departments in Phoenix, Arizona.
They are overcrowded. Ambulances go on divert for hours,
sometimes days at a time. People wait long periods of time, and
yet the volume still is increasing. Let's add on to that
another few hundred thousand people wanting to seek care in the
emergency department. The system is overwhelmed.
Let's assume that there is a bad pathogen that has been
detected, and what happens is the normal human response is they
will go to the hospital emergency department. They are not
going to wait for an ambulance to take them, they are not going
to wait for crowd control. They are worried about themselves
and their family and they respond.
The potential to contaminate the hospital is very real,
thereby literally taking that hospital off line because it is
now a contaminated environment. The ability to have something
like Dr. Trent was talking about in the triage, in the sorting
of the patient prior to entry into the medical system, just as
we are now doing with the Federal response level, which is
decontamination--we are learning how to decontaminate people
before they get into the facility in large numbers.
If you add this type of device to that triage process, so
there is a decontamination and there is a testing for exposure,
then at that point you are kind of narrowing into the funnel in
here and out would shoot the people who really have been
exposed. And those that need the hospital services now would be
decontaminated and now they can enter the health care facility
and now they can be treated. So not only on line diagnosis, but
part of the triage for a mass casualty event of a biopathogen.
Chairman Kyl. Well, is the advantage here that, A, you
could do it very quickly, and, B, you could it much more
precisely and therefore target whatever relief is appropriate
in each case? That is kind of what I am hearing, that some kind
of device that quickly tests would be far quicker and therefore
more efficient to triaging hundreds of thousands of people than
current techniques. Is that correct?
Dr. Meislin. Yes. We really have no current techniques. I
mean, we have nothing down at the level of the hospital at this
point in time. But you are absolutely right on both counts. It
has the ability on the one-to-one level; it has the ability in
a mass casualty event to triage multiple people. So you don't
overwhelm health care facilities. You are allowed to be
selective with respect to who is contaminated.
Chairman Kyl. So this is not a matter of either/or; that is
to say either sensors or a quick and efficient and
comprehensive way of triaging and diagnosing. This truly is
complementary.
Would that be a fair statement, Dr. Keim?
Mr. Keim. Yes. If I could just add that the forensic
analysis and the highly precise identification methods that we
have been developing are obviously going to be very important
for this diagnostic device. Likewise, those same techniques are
moving into the detector arena and providing a type of
specificity as things are being detected. There is no doubt
that the detector devices can recognize anthrax. In fact, in
the future they will be able to detect exactly what type of
anthrax and whether they are virulent or not.
Chairman Kyl. Let me, if I could, just walk through a
hypothetical attack with anthrax. And before I do that, let me
ask you this: There have been a lot of strains of anthrax
collected around the world, including some from sources that
may have something to do with terrorism. Let's say you are an
organization that has produced an anthrax strain and you have
had to move on.
How difficult is it to reconstitute that strain and produce
it for some possible terrorist kind of attack, number one? And,
number two, walk through the process by which you would deal
with that after it is first detected today and then with the
kind of diagnostic capability that we are talking about
developing here.
Mr. Keim. Well, the good news is I don't actually know how
to make anthrax into a weapon. It is not something that we
studied in graduate school. So, in fact, that expertise is not
commonly available in U.S. laboratories now, given that the
U.S. stopped doing this type of production back in the 1960s.
It is a little bit tough for me to answer that question, in
fact, since I don't work in public health.
Harvey, would you--
Chairman Kyl. Let me just go back to the question of--I
wasn't really referring to you making anthrax as much as I was
a terrorist who might have had the capability. Do you need a
big laboratory to do this? Do you need special vacuum chambers
or something like that?
Mr. Keim. I can talk about it in general. Anthrax, in fact,
is a surprisingly safe organism to work with in the laboratory.
There have been very few cases of laboratory infection with
this pathogen. In fact, historically it was an important
pathogen for developing the scientific theory of infectious
diseases partially because scientists could work with it
safely. The vaccines are pretty effective and there is
antibiotic treatment. So it is only considered what we would
call a Class II pathogen on a scale from I to IV.
Likewise, terrorists would have that same advantage in
being able to work with it without killing themselves. Smallpox
and some other things might be more dangerous, in fact. Anthrax
is available in many, many parts of the world, especially in
the developing world where it is a common disease. Even in this
country, we have scores of cases of animals dying of anthrax
every year. So you have to think that as a source it would be
possible for terrorists to get a hold of it. Again, then the
routine handling would be relatively safe. Scaling up and
turning it into a weapon is more difficult for me to say since,
again, it is not something that I know very much about.
Chairman Kyl. But the way that you would ordinarily deal
with it--if it came into an emergency room, what would the
process be?
Dr. Relman. I am an infectious disease clinician, so I too
deal with this kind of scenario. If someone comes into the room
right now with this as a possibility, after a routine history
and physical the kinds of things you would do today are draw
blood and send it off for a culture, which would take probably
24 to 48 hours to give you a result. You would send off
additional blood for antibody detection, which would again take
days to detect and after exposure might not even be present--
that is, the antibodies--until weeks later.
You might do a chest x-ray looking for the tell-tale signs
of inhalational anthrax, but those signs only show up days into
the clinical illness at a time point when there is very little
you can do. So all of these routine, currently available
approaches give you interesting information, but in general
well past the point when you can intervene and help the person.
Chairman Kyl. Dr. Meislin.
Dr. Meislin. I think the core answer to your question is
unless we thought about it, we wouldn't do anything; we
wouldn't know. Has any physician seen anthrax other than in
these situations where there is an attack or a lab event?
Anthrax pneumonia looks like other pneumonias. The presentation
of signs and symptoms of these pathogens look like other common
things. We don't think about it.
This gets back to the zebra thing. You know, when you hear
hoof beats, you think of horses and you don't think of zebras
because common things occur commonly. So the reality is we
would probably not do anything; in many cases, probably just
send the patient back into the environment.
So one of the other advantages of these medical devices is
that they become passive to the user. In other words, you put
in your specimen and your specimen looks for things that you
aren't thinking about. It looks for the common, it looks for
the rare, it looks for the weaponized, and it gives you the
answer without you even thinking about it, because I can
guarantee you there is nobody in an emergency department today
in this country, if someone comes in with pneumonia, that is
thinking of anthrax. It just isn't happening.
Chairman Kyl. I haven't let you talk enough about the
benefits to the development of these diagnostic capabilities
here with respect to non-terrorist incidents. I mean,
obviously, if you have got this kind of capability, it is just
enormously helpful--and I presume there are great cost savings
associated with the ability to detect with a great deal of
certainty precisely what is going on in somebody's body when
they are not feeling well. Maybe we should spend just a second
talking about that aspect of this.
And then the last question I am going to ask you really is
what do you think we need to do and what can the Government do
to assist in the research and development here. This is basic
research that we are doing that we hope to be able to apply at
some point, but what can we do?
But first of all, I think we would be remiss if we didn't
focus just a little bit on the broader public health benefits
to the development of this kind of technique. Whoever would
like to speak to that, please do.
Dr. Meislin.
Dr. Meislin. Well, let me address it, and this probably
goes into Dr. Relman's world, but the simple ability to tell a
virus versus a bacteria. Think of the thousands of times a day
across the country people go to their physician's office or to
an emergency department with a sore throat or with ``I have got
a little fever and I have got some aches,'' or ``I have a
little nausea and vomiting,'' thousands and thousands of times
a day.
The ability of the physician to understand what is going
on--is it just a virus versus a bacteria, knowing that if it is
a virus, I am not going to give you antibiotics? Think of the
effect, then, of the amount of antibiotic usage, the lack of
resistance to the antibiotics we have today, which is a huge
problem we have where we are trying to develop more antibiotics
at a huge cost to our society.
The ability to reassure patients of what is going on and
the length of their illness and what they should expect is
huge. The advantage to day-to-day medicine is just phenomenal.
I think it would be a huge cost saving. I think it would
advantage emergency departments everywhere because probably 30
to 40 percent of these types of patients present to emergency
departments. This would be a huge benefit to American medicine
just on an everyday, routine thing. And then if you want to be
more specific, the ability to tell which virus or which
bacteria, to know which sensitivities to which drugs, is just a
phenomenal benefit to everybody.
Chairman Kyl. So in one sense, the tremendous burden that
the emergency rooms have now, the challenge that is presented
to us from a public health standpoint of figuring out how to
better deal with this, could actually be alleviated to some
extent by having this kind of technique available to more
efficiently do the job that emergency rooms today are not as
well equipped to handle.
Would that be a fair statement, Dr. Meislin?
Dr. Meislin. Senator, I think you are talking probably 30
percent, maybe even more of emergency department visits would
be aided with devices like this, of people who either don't
have to come or people who could come and be treated very
quickly and then go home.
Chairman Kyl. Dr. Relman.
Dr. Relman. Even if the only thing that such a device could
do would be to distinguish those who feel terrible and have a
low-grade fever but who can go home, because we know that 48
hours from now they are not going to be sick, from those who
feel identically and cannot be distinguished from the former by
any physician but who need to be in a hospital and stay, that
ability to distinguish between those two groups of people who
today we cannot distinguish between--that ability alone would
provide incredible savings in terms of our health care
resources.
Chairman Kyl. In this sense, then, is it not true that the
human body itself is a sensor and if you have this technique,
you can much more efficiently and quickly and with better
results, then, use that sensor to determine what the
appropriate course of action is?
Dr. Relman. Exactly, and I think as I was saying, the best
old-time doctors are those that know how to look at somebody
and somehow intuit what is going on, whether it is serious or
not. We are always taught you can look at a patient and
sometimes tell if they are sick or not. Well, the truly gifted
might be able to do that, but the average doc can't quite do
that, and this is what we are hoping this device could do.
Chairman Kyl. Dr. Trent, did you have something on that?
Mr. Trent. Well, just that again I believe absolutely that
the Government can play a major role, and has done so very
effectively in the past through the competitive process, and
that is the area that we strongly support. But the end-to-end
solutions of combing molecular signatures that we have talked
about with the diagnostic platform technologies that we have
talked about with a national information architecture and
decision support system and looking at that as a unified
program is really a critical component for trying to have this
be effectively introduced and effectively bring value.
So I strongly believe that the addition of, as you said,
the body as a sensor should be part of the competitive platform
that is considered by the Government in trying to initiate our
ability to hopefully result in a critical needs and biodefense,
but also, as you have heard, improve public health and safety.
Chairman Kyl. If we just look at this in terms of cost and
forget for a moment the wellness that results from this, but
just looking at the cost, is there a way to quantify the cost
of our current system and the kinds of cost savings that could
result if we could develop and use this technology? Maybe that
is a question that you could think about it and maybe if you
could supply an answer for the record after you think about it
a little bit, that would be very helpful, or to even give us a
way of trying to calculate that cost it would be very helpful.
Let me conclude with this. It is clear to me that all the
way from the huge burden that we have in running a Government
Medicare system--I mean, that is something that the Federal
Government is directly responsible for--to our veterans care
programs, our support for the States in their Medicaid programs
and our general research through NIH and others that attempt to
help with public health all over the country--you combine that
with the benefits from an antiterrorism standpoint and you have
got a potential here that clearly should attract the attention
of the United States Government in terms of what it can do to
promote this kind of research.
So my last question is--and you were actually getting to
this in a couple of the answers, Dr. Trent--what are the best
ways for us to look at this as members of the Senate to be able
to support this kind of activity, again appreciating that it is
not a substitute for anything else, but could be very
complementary to other things that are already being supported?
Mr. Trent. Well, again, I think you just said it extremely
well. I think that the unification of interests across the
various elements of the Government is, I think, being focused
appropriately on this type of effort. So on this panel are
individuals that work with CDC, that work with NIH, that work
with the defense community and a number others.
I think that the type of coordinated programs that again
rely on competitive winnowing of responses to ensure the
excellence in science and opportunities is critical across this
entire spectrum of response that we need to put into place. So
I believe that it can't be as simple as saying that the body as
a sensor belongs to NIH and the sensor technology belongs to
CDC.
I think that really those integrated components that bring
all of those together and focus on that are really very
essential. And having lived within one small element for a
decade of the Federal Government, I think those opportunities
you have to broaden the discourse between groups is important
in many regards, and I think that is one area that you could
play a role.
Chairman Kyl. Thank you.
Dr. Keim.
Mr. Keim. I would just add that this is an enormous task to
put together a large program like this and it is going to
require components from different types of entities. On the one
hand, we are going to need large science, and that is where
agencies bring together--you know, this is like NASA putting
somebody on the moon. You bring together people who can put
together a nationwide program.
At the same time, we can't ignore the fact that a lot of
the innovation is going to come from small, what we call
principal investigator-driven laboratories, where you will see
innovative science going on, where you are getting graduate
students trained. So we have to have kind of a union with that.
On top of all of that, we have to have some type of a
commercial engine involved with this, companies that can
actually power the implementation of this, because ultimately
it is going to be delivered not by the Government; it is going
to be delivered by some U.S. or international consortium of
companies. So the problem is multi-faceted and we can't ignore
any of these. Otherwise, it won't work.
Chairman Kyl. Does anybody else have anything to add?
Again, we will keep the record open for a week for
questions, and there probably will be some. And anything else
you would like to supplement the record with we would be happy
to get.
I might just say one thing. Senator Feinstein was
addressing a question that had come up in hearings that we had
held many, many months ago about the vulnerability of our
system. I realize that none of you are in a position to answer
those questions and I would just indicate that one way or
another we will try to address that question probably with
people at the Department of Homeland Security. I am sure you
will be interested in the results of that, as well, and we will
get that information back to you. If you have anything else you
can add to that, fine, but I know that is not your area of
responsibility.
We are literally five minutes ahead of schedule here and I
want to thank all of you for keeping to the time constraints
that we set out and for very concisely but clearly and, in my
view, in a very helpful way not only bringing attention to the
problem and the challenges, but offering a very constructive
and potentially very beneficial way of addressing not just the
public health problem, but the problem of a potential terrorist
attack.
We will certainly share the results of this hearing with my
colleagues. We will write up a summary and get it to everyone.
Anything else over the course of time that you would like to
present to us that would help us to continue to appreciate how
this is evolving I would invite you to submit to us. So thank
you again very much for testimony.
If there is nothing else, I will declare this hearing
adjourned.
[Whereupon, at 10:57 a.m., the Subcommittee was adjourned.]
[Submissions for the record follow.]
[GRAPHIC] [TIFF OMITTED] T5240.001
[GRAPHIC] [TIFF OMITTED] T5240.002
[GRAPHIC] [TIFF OMITTED] T5240.003
[GRAPHIC] [TIFF OMITTED] T5240.004
[GRAPHIC] [TIFF OMITTED] T5240.005
[GRAPHIC] [TIFF OMITTED] T5240.006
[GRAPHIC] [TIFF OMITTED] T5240.007
[GRAPHIC] [TIFF OMITTED] T5240.008
[GRAPHIC] [TIFF OMITTED] T5240.009
[GRAPHIC] [TIFF OMITTED] T5240.010
[GRAPHIC] [TIFF OMITTED] T5240.011
[GRAPHIC] [TIFF OMITTED] T5240.012
[GRAPHIC] [TIFF OMITTED] T5240.013
[GRAPHIC] [TIFF OMITTED] T5240.014
[GRAPHIC] [TIFF OMITTED] T5240.015
[GRAPHIC] [TIFF OMITTED] T5240.016
[GRAPHIC] [TIFF OMITTED] T5240.017
[GRAPHIC] [TIFF OMITTED] T5240.018
[GRAPHIC] [TIFF OMITTED] T5240.019
[GRAPHIC] [TIFF OMITTED] T5240.020
[GRAPHIC] [TIFF OMITTED] T5240.021
[GRAPHIC] [TIFF OMITTED] T5240.022
[GRAPHIC] [TIFF OMITTED] T5240.023
[GRAPHIC] [TIFF OMITTED] T5240.024
[GRAPHIC] [TIFF OMITTED] T5240.025
[GRAPHIC] [TIFF OMITTED] T5240.026
[GRAPHIC] [TIFF OMITTED] T5240.027
[GRAPHIC] [TIFF OMITTED] T5240.028
[GRAPHIC] [TIFF OMITTED] T5240.029
[GRAPHIC] [TIFF OMITTED] T5240.030
[GRAPHIC] [TIFF OMITTED] T5240.031
[GRAPHIC] [TIFF OMITTED] T5240.032
[GRAPHIC] [TIFF OMITTED] T5240.033
[GRAPHIC] [TIFF OMITTED] T5240.034