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95–240 PDF 2004

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

(

(II)

COMMITTEE ON THE JUDICIARY 

ORRIN G. HATCH, Utah, Chairman 

CHARLES E. GRASSLEY, Iowa 

ARLEN SPECTER, Pennsylvania 

JON KYL, Arizona 

MIKE DEWINE, Ohio 

JEFF SESSIONS, Alabama 

LINDSEY O. GRAHAM, South Carolina 

LARRY E. CRAIG, Idaho 

SAXBY CHAMBLISS, Georgia 

JOHN CORNYN, Texas 

PATRICK J. LEAHY, Vermont 

EDWARD M. KENNEDY, Massachusetts 

JOSEPH R. BIDEN, JR., Delaware 

HERBERT KOHL, Wisconsin 

DIANNE FEINSTEIN, California 

RUSSELL D. FEINGOLD, Wisconsin 

CHARLES E. SCHUMER, New York 

RICHARD J. DURBIN, Illinois 

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 

ARLEN SPECTER, Pennsylvania 

MIKE DEWINE, Ohio 

JEFF SESSIONS, Alabama 

SAXBY CHAMBLISS, Georgia 

DIANNE FEINSTEIN, California 

EDWARD M. KENNEDY, Massachusetts 

JOSEPH R. BIDEN, JR., Delaware 

HERBERT KOHL, Wisconsin 

JOHN EDWARDS, North Carolina 

STEPHEN HIGGINS, Majority Chief Counsel 

DAVID HANTMAN, Democratic Chief Counsel 

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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

(1)

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, 

2

‘‘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 medicallybased 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 

3

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. 

4

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 

5

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. 

6

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. 

7

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 

8

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 diseaseVerDate 0ct 09 2002 08:51 Aug 12, 2004 Jkt 095240 PO 00000 Frm 00012 Fmt 6633 Sfmt 6633 S:\GPO\HEARINGS\95240.TXT SJUD4 PsN: CMORC
9

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 

10

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 endto-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 

11

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. 

12

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. 

13

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 

14

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. 

15

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 

16

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 divVerDate 0ct 09 2002 08:51 Aug 12, 2004 Jkt 095240 PO 00000 Frm 00020 Fmt 6633 Sfmt 6633 S:\GPO\HEARINGS\95240.TXT SJUD4 PsN: CMORC
17

idend 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 

18

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 

19

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. 

20

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 detecVerDate 0ct 09 2002 08:51 Aug 12, 2004 Jkt 095240 PO 00000 Frm 00024 Fmt 6633 Sfmt 6633 S:\GPO\HEARINGS\95240.TXT SJUD4 PsN: CMORC
21

tor 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 

22

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 

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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 lowgrade 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 oldtime 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?

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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 GovVerDate 0ct 09 2002 08:51 Aug 12, 2004 Jkt 095240 PO 00000 Frm 00028 Fmt 6633 Sfmt 6633 S:\GPO\HEARINGS\95240.TXT SJUD4 PsN: CMORC
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ernment, 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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