Mr. Chairman and members of the Committee, thank you for the opportunity to participate in this hearing. Before sharing my views, some comments about my background may be helpful. My name is Gail Cassell.I am a microbiologist currently serving as Vice President for Scientific Affairs and Distinguished Research Scholar in Infectious Diseases, Eli Lilly and Company.Prior to my arrival at Lilly five years ago, I was the Charles H. McCauley Professor and Chairman of the Department of Microbiology of the University of Alabama Schools of Medicine and Dentistry, Birmingham, Alabama.My background is that of a research scientist in infectious diseases working in laboratories of both industry and a research-intensive university as well that of a Director of large training programs for pre- and postdoctoral students in molecular genetics, virology, and immunology.I have served on the Advisory Committee of the Director of the National Institutes of Health (NIH) and on the Advisory Council of the National Institute of Allergy and Infectious Diseases of the NIH and as Chair of the Board of Scientific Councilor's of the National Centers for Disease Control and Prevention (CDC).I am currently a member of the Director's Advisory Committee of the CDC.Over the years, I have participated in reviews of the biomedical research programs (including bioweapons defense research) in the Department of Defense.Of particular relevance to the discussions today, I have been actively involved in issues related to biodefense for over the past decade, as a past President of the American Society for Microbiology (ASM), Chair of the Public and Scientific Affairs Board of the ASM and a member of ASM's Task Force on Biological Weapons.I served as Co-chair of the committee that reversed the decision to destroy the U.S. stocks of smallpox and as a member of the Advisory Committee to establish the first unit in the U.S. military to address a bioweapons attack on U.S. soil.In addition, I continue to serve on a number of committees in the National Academy of Sciences (NAS) dealing with bioweapons, including a Russian research advisory committee. Most recently I served on the Bioweapons Subcommittee of the NAS Committee on Science and Technology for Countering Terrorism.
The events of September 11, and the anthrax incidents which followed, have proven the vulnerability of the United States to terrorism and the complexities of preparedness.The need to strengthen planning, coordination, implementation and oversight of homeland security is obvious.The establishment of a new federal Department of Homeland Security, at a cabinet level, can potentially achieve greater efficiency, effectiveness and accountability regarding many aspects of terrorism.However, there are unique characteristics of bioterrorism that deserve special consideration and suggest the need to address them in a manner differently from that proposed by the Administration's Bill.These characteristics include:(1) inadequacy of existing countermeasures and urgent requirement for interdisciplinary research; (2) indistinguishable features of bioterrorism and naturally occurring infectious diseases; and (3) the nature and extent of the bioterrorism threat and the need to balance public safety and legitimate research in regulation and oversight measures.
1. Inadequacy of existing countermeasures and urgent requirement for interdisciplinary research
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 constant surveillance, accurate diagnostics to identify threats as early as possible, and continuous innovation to provide 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 new antibiotics, antivirals, diagnostics and vaccines.The research and development of technologies for biodefense should be synergistic and not duplicative.
The diversity of existing biological weapons and the ever-increasing possibilities preclude simple therapeutic countermeasures to bioterrorism.Furthermore, response possibilities are limited even for known threats.Although there are 13 viruses on the current select agent list, there is only one antiviral, which is for smallpox and must be administered intravenously.There are no truly broad-spectrum antivirals, and only a limited number of antivirals for routine pathogens like influenza, herpes, hepatitis B, and HIV.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 three decades. The Russians are known to have constructed antibiotic resistant bioweapons.In short, our antibiotic armamentarium is limited, and there is growing concern about an increase in resistance to existing antibiotics.It seems clear that no public health response to bioterrorism is likely to prove effective without addressing the overall problem of antimicrobial resistance and the challenges of drug discovery and development.Finally, the best deterrent against the use of a biological weapon of mass destruction may be a constant stream of new, innovative antibiotics, antivirals, and vaccines.Knowledge of such commitment and successful developments would surely dissuade the efforts of our enemies in such an arena.
Development of these 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, antivirals, and immunomodulators.Equally important will be to benefit from knowledge gained in previous failures in countermeasure development efforts.Given the long lead-time necessary for development of vaccines and drugs (average 8-10 yrs), achieving timelines and goals are critical.
The magnitude of the challenge to develop effective countermeasures is great.Success will require involvement of the very best scientific, medical, and pharmaceutical 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 expertise of and existing infrastructure for product development that resides in the pharmaceutical industry.Engaging the full spectrum of private industry, i.e., from the smallest biotech to the largest pharmaceutical companies, in the search for solutions to infectious diseases, will not only greatly raise the chances of success, it can also significantly lower the total cost to taxpayers, augmenting public appropriations with private capital investment.Thus, it is critical to recruit these organizations into the biodefense effort and assure effective alignment between government, academia and industry.
The NIH recognizes that significant advances occur when they are often unforeseen.These advances expand the experimental possibilities and open new pathways for research.It must be recognized that not all research problems are equally approachable no matter how urgent and important to public health.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 that will yield solutions.NIH/NIAID is unrivaled in its track record of bringing together the brightest 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 which 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.They can quickly mobilize the research community.Last fall, the NIAID conducted a study to show that existing stocks of smallpox vaccine could be diluted at least 5-fold to provide immediate protection to a larger number of individuals should the need arise.Within three months 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.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 and immunology 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 recommend that the Department of Health and Human Services (HHS) continue to be responsible for the prioritization, direction, and conduct of federal research efforts related to development of countermeasures for bioterrorism.
Although the Administration's Bill recognizes the necessity that HHS conduct the research and development programs related to infectious diseases, Section 303(a)(2) of the Bill provides that DHS, in consultation with HHS, shall have final authority to establish the research and development program, including the setting of 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 non-scientific, non-public health based agency.To create the appropriate scientific infrastructure in DHS would result in loss of momentum and unpredictability of new and ongoing research programs within HHS.There is no time to "re-invent the wheel" rather we should capitalize on the solid infrastructure that already exists in 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 merit review.
In summary, a scientific health agency, HHS, rather than the non-scientific, 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 into the research agenda.This could be accomplished by appointment of an Assistant Secretarythat would have dual reporting to HHS and DHS and to work closely with NIH/NIAID.The desired outcome would be mutually agreed upon research priorities that address threatening biological agents.
2. Indistinguishable features of bioterrorism and naturally occurring infectious diseases
While bioterrorism poses grave threats, the human race has been ravaged by infectious diseases throughout its history.The emergence of new infectious diseases (notably HIVAIDS) has decimated entire societies, while infectious agents such as influenza can turn unexpectedly virulent, e.g. the 1918 influenza pandemic killed tens of millions of people.In this broader context of emergent and resurgent infectious disease, the victims of a bioterrorist attack pose an indistinguishable set of public health challenges from any number of foreseeable natural outbreaks.Since well over 30 previously unknown infectious agents (including several new hemorrhagic fever viruses and new highly virulent strains of streptococci) have been identified since 1973, it is imperative that our public health infrastructure and surveillance systems be structured to recognize both naturally occurring and intentionally released infectious agents.CDC shouldhave this responsibility.Section 505(a)(2) of the Administration's Bill requires DHS to carry out these functions under agreement with HHS.A separate public health system for biodefense should not be created.The primary duty and authority should remain with CDC, which has the existing knowledge, experience, and expertise.Again, an Assistant Secretary with dual reporting to HHS and DHS could coordinate planning and development of programs and lend technical assistance.Working closely with the CDC Director mutually agreed upon public health priorities for bioterrorism preparedness and response could be achieved in an efficient manner.
3. The nature and extent of the bioterrorism threat and the need to balance public safety and legitimate research in regulation and oversight measuresBiological weapons have varied characteristics.High potency, substantial accessibility, and relatively easy delivery characterize the most fearsome agents.Humans, animals, and plants are potential targets for bioterrorism.Many of these agents-bacteria, viruses, and toxins-occur naturally in the environment.Thus the agents and much of the technology required to produce them are available for civilian or military use in many countries.Regulation and oversight measures for work with infectious agents must be balanced so as not to impede legitimate research, diagnosis, and treatment of these naturally occurring infectious agents.I recognize that there is public concern 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.The response taken should be carefully weighed and it should be balanced to avoid over regulation and intrusive schemes that could interfere with the flow of research activities in academia and industry.Any resulting harm to research could deprive society of the benefits of research advances. Scientific research must not be discouraged by unreasonable restrictions.To do so would not serve the public interest.
In reviewing the possible risks and options for responses, we should consider emulating the process used in overseeing recombinant DNA research.This experience is an example of where a technical problem was recognized and a balanced analysis and an appropriate mechanism were set in place for overseeing activities.The NIH Recombinant DNA Advisory Committee developed a rational approach to regulatory oversight of recombinant DNA.The NIH Guidelines were developed by a committee of experts and an oversight regime was designed with an understanding of the issues and risks.We should use the same model to construct a reasonable method that will not impede research or result in unnecessary costs.Institutions must take a proactive role in assuring that hazardous agents are brought into or shipped from their facilities and used in compliance with applicable regulations.The most effective approach to adequate oversight and record keeping is for institutions to monitor possession, transfer and use of select agents.Placing responsibility at the level of individual institutions for compliance with Title II of HR 3448 will be the least inhibitory to research.
It is important to coordinate programs related to human, animal, and plant agents because some of the threats for each are the same.Section 302(a) of the Administration's Bill transfers to DHS the selectagent registration and enforcement programs of HHS.However, it does not transfer the select agent registration and enforcement programs ofthe Department of Agriculture to the DHS.Subtitle C of the Public Health Security and Bioterrorism Preparedness Act of 2002 mandated coordination of activities of HHS and the Secretary of Agriculture regarding "overlap agents"-that is, agents that appear on the separate lists prepared by HHS and Agriculture.Title II of that legislation expands the current select registration program to include mandatory registration of possession of select agents.Mr. Chairman, the Energy and Commerce Committee is to be congratulated for their role in this important legislation.Indeed, integration of the select agent registration program will undoubtedly result in a more efficient registration process thereby expediting registration.
Coordination among agencies that have regulations for infectious substances is important. Better compliance can be achieved if regulations are clear and coherent, streamlined and integrated, based on real risks, and effectively communicated to individual researchers.Emphasis must be placed on education, guidance and dissemination of information to research investigators, who must clearly understand their role and responsibilities.Institutional Biosafety Committees can be strengthened and there should be qualifications and training for institutional biosafety officers.Laboratory scientists and safety managers in institutions must have input into the rule-making procedures and work to assure that regulations are realistically applied with minimal intrusiveness.
The core elements of a regulatory regime are already in place in 42 Code of Federal Regulations Part 72 and in the Biosafety and Microbiological and Biomedical Laboratories (BMBL) Manual.Appendix F includes guidelines for Laboratory Security and Emergency Response for Microbiological and Biomedical Laboratories.Although it is currently nonspecific, it is a reasonable basis for the development of biosecurity requirements.It should be possible for HHS to modify its current regulatory regime to govern registration for possession and build on the BMBL guidance to provide for threat and risk based regulations.Security for select agents should be based upon risk levels.
HHS has the best scientific and institutional knowledge to provide oversight of select agent registration and to develop rational enforcement programs.The scientific communities, both in universities and in the private sector, are accustomed to self-regulation in use of radioactive materials, chemicals, and infectious agents.This service is provided by institutional Biosafety Offices.Likewise, review of protocols and inspection and accreditation of facilities are the norm for use of laboratory animals in research.Again, implementation of regulations related to select agents is reminiscent of the oversight put in place with the advent of recombinant DNA technology.In short, once the regulations have been established, implementation can be achieved through use of a system modeled after Biosafety Office Programs already in existence.
I believe the program for select agents should remain within HHS.To transfer it to DHS will result in a delay to implementation, which could considerably slow down implementation of the biodefense research agenda.More importantly, housing it within DHS could result in undue tension with the research community.For example, it is unclear whether the regulations to be put in place within the next 180 days will be changed taking on more of a criminal approach rather than one based upon scientific knowledge and insights into the biomedical research process utilizing infectious agents.The Administration's Bill states that interim regulations will be put in place thereby leaving freedom following the transfer of authority to DHS for other regulations to be drafted.
In summary, I support Title II and its protections for the legitimate and critical performance of research and diagnostic testing.Security for biological facilities is different from security for nuclear and chemical facilities and must take into account the unique aspects of work with biological agents.Inappropriate policy measures and regulations to prevent terrorists from acquiring pathogens could have unintended consequences for research aimed at developing the very countermeasures that could eventually remove agents from the select agent list.There needs to be a careful balancing of public concern about safety and security with the need to conduct legitimate research to protect the public.Because of the enactment of HR 3448, which again the Energy and Commerce Committee and this Subcommittee had direct responsibility, the United States is in a leadership position with regard to the establishment of reasonable controls on select agents.However, we should not have a false sense of security since no other country in the world has adopted similar legislation, which will be necessary.Ultimately, successful oversight will depend upon the integrity of the personnel who have access to select agents and on local institutional commitment.
Again, I appreciate having been given the opportunity to share my views and concerns with you.The inadequacy of our current public health infrastructure and existing biomedical defenses against a range of possible bioterrorist attacks has become clear.This inadequacy has, moreover, served to underscore the already well-documented need for better and more varied antimicrobials, vaccines, and other agents to detect, prevent or treat infectious diseases.One likely outcome from increased attention to bioterrorism threats will be the development of more comprehensive public health measures and countermeasures to threats posed by naturally occurring infectious diseases.I believe the recommendations I have made today provide the greatest chances for success.