June 6, 2003
Mr. Chairman and Members of the Committee, thank you for giving me the opportunity to discuss the comprehensive and accelerated process for developing medical countermeasures against bioterrorist threats. As you know, the National Institutes of Health (NIH), particularly the National Institute of Allergy and Infectious Diseases (NIAID), of which I am Deputy Director, is engaged in a vigorous effort to ensure homeland security and protect the American people against potential agents of bioterrorism as well as emerging and re-emerging infectious diseases.
The destruction of the World Trade Center, the attack on the Pentagon, and the anthrax attacks in the fall of 2001 starkly exposed the vulnerability of the United States to acts of terrorism. At the NIH, and particularly at the NIAID, these events triggered the development of an aggressive, broadly based research program designed to provide the American people with vaccines and therapeutics against a range of bioterrorist threats.
Integral to this effort is the enactment of Project BioShield, which will increase the authority and flexibility of NIH to expedite research toward the development of critical medical countermeasures for biodefense. Project BioShield would also establish a secure funding source for the purchase of critical medical countermeasures, and would give the Food and Drug Administration (FDA) an Emergency Use Authorization for these countermeasures. Thus, the accelerated research and development program of the NIH, and the NIAID in particular, would work in concert with Project BioShield to provide the American people with safe and effective vaccines and therapeutics to protect them against a range of biological threats.
Today, I will describe to you: (1) how the NIAID has set its research priorities to develop vaccines and therapeutics against bioterrorist threats; (2) why NIAID has identified certain biological agents as its top research priorities; and (3) what NIAID is doing to ensure that medical countermeasures - particularly vaccines and therapeutics - are developed as rapidly as possible to protect homeland security.
For years, civilian agencies such as the NIH, the FDA, the Centers for Disease Control and Prevention (CDC), as well as the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in the Department of Defense (DoD), have addressed the threat of bioterrorism. The research has been directed at viruses, bacteria, and bacterial toxins that could emerge or re-emerge spontaneously in nature, or that could be intentionally released as biological weapons into human populations. However, the anthrax attacks of 2001 revealed significant gaps in our overall preparedness against bioterrorism, and gave a new sense of urgency to our biodefense research efforts.
We realized quickly that it was no longer adequate to do business as usual. A primary goal of the NIH has always been to support research efforts that generate new knowledge about disease and to translate these findings into vaccines, therapeutics, and diagnostics that protect public health. But, to develop safe and effective products for biodefense as quickly as possible, we needed to intensify and accelerate this process. Thus, we sought creative ways in which to modify NIH's traditional process of research and development, while continuing to preserve the excellence that is a hallmark of NIH research. The NIAID biodefense research program is directed primarily toward the needs of civilian populations, although interventions emerging from it may logically also have application in military settings.
How has NIAID set its research priorities to develop vaccines and therapeutics against bioterrorist threats?
Bioterrorism is defined as the intentional use of microorganisms that cause human disease, or of toxins derived from them, to harm individual people or to elicit widespread fear or intimidation of society.
The NIAID set its research priorities for defense against bioterrorism through a comprehensive and systematic process. Since February of 2002, we have convened four multi-institutional panels of scientific experts, and developed a strategic plan and strategic research agendas based on their recommendations. Based on advice from the Blue Ribbon Panel on Bioterrorism and Its Implications for Biomedical Research, we developed the NIAID Strategic Plan for Biodefense Research and the NIAID Research Agenda for CDC Category A Agents. The Strategic Plan emphasizes: 1) basic research on microbes and host defenses; and 2) targeted, milestone-driven development of drugs, vaccines, other interventions, and diagnostics. The NIAID Biodefense Research Agenda emphasizes the short-term, intermediate, and long-term goals for research on Category A agents, a group of microbes and toxins identified by the CDC as the most dangerous. These include anthrax, smallpox, plague, botulism, tularemia, and hemorrhagic fevers caused by viruses such as Ebola.
Thus, the initial focus of our biodefense research effort has been to develop new and improved vaccines, therapeutics, and diagnostics against Category A agents. An essential component of this program is enhancing the Nation's capability to conduct research on these agents. This requires that additional high-containment research facilities, known as BioSafety Level-3 (BSL-3) and BSL-4 laboratories, be constructed and made accessible to government-supported scientists. Also required to fulfill the goals of our research program are other specialized research resources such as centers for sequencing the genomes of these microbes, and skilled scientists and technicians who are trained to handle dangerous microbes and toxins.
In addition to research on Category A agents, NIAID is also spearheading efforts to develop new and improved vaccines, therapeutics, and diagnostics for Category B and C agents. Again, based on the recommendations of a blue ribbon panel, we developed the NIAID Biodefense Research Agenda for Category B and C Priority Pathogens. These agents include a diverse array of viruses, bacteria, and bacterial toxins that are carried by insects, livestock, or other vectors; can be inhaled; or are spread through contaminated food and water. They include the bacteria that cause typhus and cholera, and viruses such as West Nile virus, which is carried by mosquitoes, and tick-borne encephalitis virus. As is the case for the Category A agents, NIAID research on Category B and C agents is designed to understand the biology of the microbe and the host response to the microbe, and to use that knowledge as the basis for developing safe and effective vaccines and other medical countermeasures.
Why has NIAID identified certain biological agents as its top research priorities?
I have already indicated that the NIAID biodefense program emphasizes research on Category A agents: anthrax, smallpox, plague, botulism, tularemia, Ebola and other hemorrhagic fever viruses. Why are these viruses, bacteria, and toxins considered the most dangerous potential agents of bioterrorism? Many other microbes, such as those that cause measles, mumps, or even AIDS, cause serious illness but are not on the Category A list. Simply put, the high-priority Category A agents include organisms that pose a risk to national security because they:
Category B agents are considered to have the second highest priority in terms of their bioterrorist threat potential. These agents are moderately easy to disseminate, result in moderate morbidity rates and low mortality rates, and require specific enhancements of our diagnostic capacity and enhanced disease surveillance. Category C agents have the next highest priority. They include emerging pathogens that could be engineered for mass dissemination in the future because of their availability, ease of production and dissemination, and potential for high morbidity and mortality rates and major health impact.
What is NIAID doing to ensure that vaccines and therapeutics are developed as rapidly as possible to protect homeland security?
The process by which NIAID is developing safe and effective countermeasures for biodefense is complex and multifaceted. I would like to describe, in general terms, how we develop vaccines. I will relate this process to the specific development of vaccines and therapeutics for biodefense.
In general, the NIAID has three broad goals in vaccine research:
To achieve these goals, NIAID supports basic research to understand the biology of the microbes that cause disease and to determine how humans and other animals respond to infection with these microbes. Key to our understanding of microbial biology is identifying the nucleic acid sequence of their genomes. With this information in hand, we will be better poised to identify molecular targets to use in the design of vaccines or therapeutics. Recently, for example, two teams of NIAID-funded researchers at The Institute for Genomic Research in Rockville, MD, reported the complete genetic sequence of the strain of Bacillus anthracis used in the 2001 anthrax mail attacks, and the complete genomic sequence of the Q-fever pathogen and Category B agent, Coxiella burnetii.
In addition to understanding how a microbe causes disease, it is also important to understand how animals and humans respond to microbial infection. NIAID supports research on innate and adaptive immune responses in a range of animal models and in humans. We also are working to understand how certain pathogens evade immune surveillance and use this information to design ways to trigger a protective immune response. We are investigating new immunostimulatory agents that boost the effectiveness of vaccines. Additionally, we need to understand how immune responses vary in different individuals according to age, general health status, genetic makeup, and treatment with immunosuppressive drugs.
Developing new and improved vaccines and therapeutics also requires a strong clinical infrastructure. NIAID supports Vaccine and Treatment Evaluation Units, which conduct human clinical trials to determine the safety and efficacy of candidate vaccines for infectious diseases, including several caused by Category A, B, and C agents. This network has served as a national resource for the independent evaluation of vaccines since 1992.
Another primary objective of the NIAID biodefense research program is to attract the long-term interest and support of academia and industry in the efforts needed to develop effective bioterrorism countermeasures. NIAID's biodefense research program facilitates the involvement of academic scientists through the use of all available funding mechanisms, including the development of a network of Regional Centers of Excellence for research on bioterrorism and emerging and re-emerging infectious diseases.
Key to the development of safe and effective medical countermeasures for biodefense are collaborations with private industry. Since the Fall of 2001, we have strengthened and expanded our interactions with the private sector, including biotechnology companies and pharmaceutical manufacturers. Many biodefense products will not provide sufficient incentives for industry to develop on their own, because a profitable market for these products cannot be guaranteed. Therefore, NIAID has developed public-private partnerships to overcome these obstacles. Also, the passage of Project BioShield, which would authorize the purchase of biodefense countermeasures, would provide a much-needed incentive to participate in this effort.
Our biodefense strategic plan and research agenda has required an expansion of investigator-initiated and Institute-initiated grants and contracts. In Fiscal Years 2002 and 2003, NIAID developed a total of 46 biodefense initiatives to stimulate research: 30 are new initiatives and 16 are significant expansions. During this same time period, NIAID has seen a 30 percent increase in the number of grant applications; the vast majority of these are in response to our biodefense initiatives.
Still another important element in our biodefense research program is an enhancement of Intramural research. Of note, the NIAID Vaccine Research Center, is working on the development of new and improved vaccines against a range of bioterrorist threats, including the Ebola virus, as well as a next-generation vaccine against smallpox.
Related to our biodefense preparedness research program is a more recent, NIH-wide effort to develop effective countermeasures against chemical and nuclear/radiological weapons. We recognize the NIH may not necessarily have a predominant role in developing countermeasures for these threats, although we must still be prepared for any eventuality. Dr. Elias Zerhouni, the director of NIH, has established the NIH Biodefense Research Coordinating Committee to facilitate and coordinate the development of a research agenda and to implement R&D programs that address relevant aspects of chemical and nuclear/radiological threats. Dr. Anthony S. Fauci, the director of NIAID, serves as committee chairman.
That concludes my testimony. I would be happy to answer any questions you may have.
Last Revised: June 10, 2003