Hamburg, Vice President, Biological Programs, Nuclear Threat Initiative.

Thank you for being with us. This committee is holding an investigative hearing. When doing so, it is our practice to take testimony under oath. Do any of you have qualms about testifying under oath?

In that case, I should also inform you that pursuant to the rules of the committee and the House, that you are entitled to be represented by counsel. Do any of you wish to be represented by counsel?

Thank you. If you will stand and raise your right hand.

[Witnesses sworn.]

Mr. GREENWOOD. Thank you very much. You are under oath. Ms. Heinrich, you are recognized for 5 minutes.

TESTIMONY OF JANET HEINRICH, DIRECTOR, HEALTH CARE AND PUBLIC HEALTH ISSUES, GENERAL ACCOUNTING OFFICE; GAIL H. CASSELL, VICE PRESIDENT, SCIENTIFIC AFFAIRS, DISTINGUISHED LILLY RESEARCH SCHOLAR FOR INFECTIOUS DISEASES, ELI LILLY AND COMPANY; AND MARGARET A. HAMBURG, VICE PRESIDENT, BIOLOGICAL PROGRAMS, NUCLEAR THREAT INITIATIVE

Ms. HEINRICH. Mr. Chairman and members of the subcommittee, I appreciate the opportunity

Mr. GREENWOOD. I think your mike is not on yet.

Ms. HEINRICH. Is that better?

I appreciate the opportunity to be here today to discuss one component of the proposed creation of the Department of Homeland Security. My remarks will focus on the potential effects of reorganization of biomedical research under Title III.

The proposed department is tasked with developing national policy for and coordinating the Federal Government's civilian research and development efforts for all threats, biological, radiological and nuclear. The new department could improve coordination of the biomedical research efforts, most of which is sponsored or conducted at the National Institutes of Health. The President's proposal could help improve coordination by giving one person the responsibility for a single national research and development agenda. In the past, we have recommended the creation of a unified strategy to reduce duplication and leverage resources, and suggested that the plan be coordinated with Federal agencies performing research as well as State and local authorities. Such a plan would help to ensure that research gaps are filled, unproductive duplication is minimized, and that individual agency plans are consistent with the overall goals.

Interagency coordination will remain essential under the proposal. It should be noted that the legislation focuses on civilian efforts only. The new department will also need to coordinate with DOD because it also conducts biomedical research geared toward protecting service members, but applicable to the civilian population as well.

NIH and DOD currently collaborate on a number of projects, such as a shared data base to compare the sequences and functions

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of pox virus genes and testing of new vaccines. This coordination needs to continue.

It also includes four academic centers, CDC, USAMRID, DARPA, and American Type Culture Collection.

Despite these positive aspects of the proposal, we are concerned about the implications of the proposed transfer of control and priority setting for dual-purpose research. The President's proposal would transfer the responsibility for biomedical defense research to the new department, but the programs would continue to be carried out by NIH. These programs include a variety of efforts to understand basic biological mechanisms of infection and to develop and test rapid diagnostic tools, vaccines, and antibacterial and antiviral drugs.

The research on biologic agents that could be used by terrorists cannot be readily separated from research on emerging infectious diseases. For example, research being carried out on antiviral drugs for biodefense research is expected to be useful in the development of treatments for hepatitis C. Research to expand our knowledge of factors that play a role in determining antibiotic resistance, virulence and invasiveness, as well as factors influencing the severity of disease, are critical to emerging infectious diseases as well as biodefense research.

In addition, the proposal would allow the new department to direct, fund and conduct research on its own. This raises the potential for duplication of efforts, lack of efficiency, and an increased need for coordination with other departments that would continue to carry out relevant research. It is inefficient to build and duplicate the expertise and facilities that already exist in the current Federal laboratories that are needed to conduct this work.

In conclusion, better coordination of research efforts could reduce wasteful duplication and increase efficiency. We are concerned, however, with the President's proposal to transfer broad control of biomedical research to the new department. Although there is a need for a strategic plan for research, there is also a need for maintaining the synergy of biodefense, emerging infectious diseases, and basic biomedical research efforts.

The R&D funding and priority setting needs to be vested at the program level best positioned to understand the benefits of both the basic and applied research efforts. If disagreements arise over priorities for biomedical research, there may need to be a mechanism for resolution within the Office of the President or in the Congressional appropriations process.

Mr. Chairman, this concludes my remarks. I would be happy to answer any questions.

[The prepared statement of Janet Heinrich appears at the end of the hearing.]

Mr. GREENWOOD. Thank you, Ms. Heinrich.

Ms. Cassell.

TESTIMONY OF GAIL H. CASSELL

Ms. CASSELL. The establishment of a new Federal Department of Homeland Security can potentially achieve greater efficiency, effectiveness and accountability regarding many aspects of terrorism. However, there are unique characteristics of bioterrorism that de

serve special consideration and suggest the need to address them in a manner differently than that proposed by the administration's bill. I will limit my comments this morning to those that directly relate to research leading to countermeasures.

There is no simple counter to bioterrorism, no magic bullet. Instead, development of an integrated set of strategies is required. Such efforts must include preventing countries from acquiring bioweapons in the first instance, dismantling existing programs and capabilities where proliferation has already occurred, deterring the use of biological weapons and ultimately putting in place countermeasures that can rapidly detect and effectively defend against such use. It is the latter that requires special consideration with respect to the proposed role of DHS.

In the long term the only way to defend against bioterrorism is through a combination of of constant surveillance, accurate diagnostics to identify threats as early as possible, and availability of high quality vaccines and drugs that can be useful against any attacks that do occur. Research related to bioterrorism is inextricably linked to that of naturally occurring infectious agents and development of the new antibiotics, antivirals diagnostics and vaccines. Thus, the research and development of technologies for biodefense should be synergistic and duplicative.

The diversity of existing biological weapons and the ever increasing possibilities preclude simple therapeutic countermeasures to bioterrorism. Currently our countermeasures are very limited, even for known threats. This is a very important consideration. There are 13 viruses on the select agent list today, yet there is only one antiviral and this is for smallpox, and it must be administered intravenously. There are no truly broad spectrum antivirals. We have only a limited number of antivirals for a few naturally occurring viruses.

The situation is somewhat better, but still worrisome with respect to antibiotics. There has only been one new class of antibiotics developed in the past 30 years. The Russians are known to have constructed bioweapons resistant to current antibiotics. While there are currently 23 antibiotics in Phase I through III clinical trials today, there are few new classes and importantly no new broad spectrum antibiotics, only more quinolones like Cipro. In short, our antibiotic armamentarium is limited and there is growing concern about an increase in resistance to existing antibiotics, exemplified by two different bills introduced within the past few months.

An idea of the problem of resistance, in fact it's now known that the E. coli strains occurring, 90 percent of these are or 50 percent of these actually are resistant. Thus it seems clear that no public health response to bioterrorism is likely to prove effective without addressing the overall problem of existence and the technical challenges of drug discovery and development.

Development of effective countermeasures will depend on interdisciplinary research ranging from basic research into the mechanisms by which the agents cause disease, how the body responds, and how the agents are transmitted. This new knowledge then must be used to develop innovative vaccines, antibiotics, and antivirals and immunomodulators. Equally important will be to

benefit from knowledge gained in previous failures in development efforts. It is important to realize while development of a new bioweapon only takes months, development of a single new drug or vaccine on average, based on many years of experience, requires anywhere from 8 to 10 years. Thus, meeting time lines and research goals are vital to our defense given our current situation.

The magnitude of this challenge cannot be underestimated. Success will require involvement of the very best scientific and medical talent in government, academia and the private sector. Likewise, in order to achieve success in a timely manner the United States must be able to capitalize upon the existing infrastructure for product development. Engaging the full spectrum of private industry from the smallest biotech to the largest pharmaceutical companies in the search for solutions will not only greatly raise the chances of success, but also significantly lower the total cost to taxpayers, augmenting public appropriations with private capital investment. The NIH, specifically NIAID, is uniquely positioned to lead this effort. The NIH recognizes that significant advances occur when they often are unforeseen. These advances expand the experimental possibilities. It must be recognized that not all research problems are equally approachable no matter how urgent and important to public health. Development of countermeasures for bioweapons is not like designing a new tank. Research and development of countermeasures will be a long-term endeavor.

There is always uncertainty about where the most valuable discoveries can be made, but NIH is best placed to identify scientific opportunities and applications that are relevant to the most pressing issues. NIAID is unrivaled in its track record of bringing the right scientists and rigorous peer review and oversight of funded research. Indeed, many of the best investigators have already been funded by NIAID and have recently made major advances in determining the mechanism of action of the anthrax toxin and the molecular mechanism by with the Ebola virus induces death.

As evidenced by mechanisms put in place early in the AIDS epidemic, NIAID has a positive track record of working with the private sector from early phase discovery to clinical development. NIAID can quickly mobilize the entire research community. Last fall NIAID conducted a study to show that existing stocks of smallpox vaccine could be diluted at least fivefold to provide immediate protection to a larger number of individuals should the need arise. Within 3 months post-9/11 a comprehensive biodefense research agenda was developed with broad input from the scientific and medical communities, including those from industry. Over 20 initiatives already have been launched to expedite biodefense research by NIAID.

This impressive efficiency is in part based upon the synergy which is derived by driving the biodefense research in parallel with all other infectious disease research. Separation of these two efforts could result in failure due to missed opportunities, failure to apply the latest technologies or knowledge gained from the study of other infectious agents. Therefore, I strongly recommend that the Department of Health and Human Services continue to be responsible for the prioritization, direction, and conduct of Federal research efforts related to the development of countermeasures for bioterrorism.

Although the administration's bill recognizes the necessity that HHS conduct the research and development programs, the bill provides that DHS in consultation with HHS shall have final authority to establish the research and development program, including the setting of research priorities. The proposed transfer of program and funding authority in the administration's bill gives ultimate control of research spending and priorities to DHS, a nonscientific, non-public, health-based agency. I will submit that you cannot wisely set research priorities without being actively engaged in research and with wise medical input from the medical and scientific investigators.

The bottom line is that DHS could under the current administration's bill change priorities midstream and by budget allocations. To create the appropriate scientific and medical infrastructure in DHS would result in loss of momentum and unpredictability of new and ongoing research programs within HHS. There is no time to reinvent the wheel. Rather it should capitalize on the solid infrastructure that already exists in the infectious disease research in this country.

It is not clear which activities by the DHS would duplicate, supplant, or replace existing programs conducted by HHS and create increased and recurring costs. One of the most critical determinants of success in biodefense research will be support and oversight of excellent science based upon peer review and merit. As stated earlier, NIH-NIAID has an unparalleled track record of success based upon external peer review. A scientific health agency, HHS, rather than the nonscientific, non-public health DHS, should have the principal authority for developing and prioritizing scientific and health related programs.

The role of DHS should be to integrate threat analysis and vulnerability assessments and research agenda. This could be accomplished by appointment of an Assistant Secretary who would have dual reporting to HHS and DHS and to work closely with NIAID. The desired outcome would be mutually agreed upon research priorities that address threatening biological agents, whether they be intentionally released or naturally occurring.

Last, regulation and oversight measures for work with infectious agents must be balanced so as not to impede legitimate research, diagnosis, and treatment of naturally occurring infectious agents. I recognize that there's concern, and I share those concerns, about pathogenic microorganisms being used as biological weapons by nations or individuals. As these concerns are addressed, however, I urge that there be careful review of possible measures that might be taken to establish appropriate safety and enforcement measures. HHS has the best scientific and institutional knowledge to provide oversight of select agent registration and to develop rational enforcement programs.

Thus, I believe the program for select agents should remain within HHS at the CDC. To transfer it to DHS will result in a delayed implementation, which could considerably slow down implementation of the biodefense research agenda. And as currently structured, I would just point out that minimal regulations are being put in place now so there's opportunity to change those obviously by DHS further down the road. As a result of this, more impor