[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



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                       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.]

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