Before the Committee
on Appropriations, Subcommittee on Labor,
HHS, Education and Related Agencies
United States Senate
S. Fauci, M.D.
Institute of Allergy and Infectious Diseases, National
Institutes of Health
of Health and Human Services
For Release on
at 9:00 am
Thursday, November 29, 2001
and Members of the Subcommittee, thank you for inviting
me here today to provide an update on the current bioterrorism
research activities of the National Institutes of Health
(NIH) and our plans for the future. Any program that will
effectively counter bioterrorism out of necessity would
be a comprehensive program involving multiple government
agencies, local and state health departments, and private
industry. An important component of such a comprehensive
effort is biomedical research. The role of the NIH in
the overall government effort against bioterrorism is
to conduct and support such research.
The NIH bioterrorism research program
is spearheaded by the National Institute of Allergy and
Infectious Diseases (NIAID) and encompasses four broad
areas: basic research, diagnostics, vaccines and therapeutics.
I would like to briefly describe our research in these
broad areas as well as summarize several specific NIAID-supported
smallpox and anthrax studies.
Research into the basic biology and
disease-causing mechanisms of pathogens underpins efforts
to develop interventions against agents of bioterrorism.
NIH supports research to better understand the factors
that influence a pathogen's virulence and invasiveness,
as well as those that determine antibiotic resistance.
NIH also supports research on the host/pathogen interactions.
Knowledge from basic research findings is crucial to the
development of preventative and therapeutic strategies.
One of the most important basic research
tools that has evolved in recent years is the ability
to rapidly sequence the entire genomes of microbial pathogens,
including potential agents of bioterrorism. Some agents,
such as smallpox and other orthopoxviruses related to
smallpox, have already been sequenced; the sequences of
others, such as Bacillus anthracis
(the anthrax bacterium) and other bacteria relevant to
bioterrorism are in progress and close
to completion. The fruits of genomics research, coupled
with other biochemical and microbiological information,
are expected to facilitate the achievement of critical
new goals, including the discovery of new targets for
drugs and vaccines. In particular, comparative genomics
(comparing the sequences of different strains of particular
organisms) will be an important component of future research,
helping us to understand what makes a particular organism
either harmful or benign.
NIH also supports research leading
to the development of new and improved diagnostics. The
goal of this research is to establish methods for the
rapid, sensitive, and specific identification of natural
and bioengineered microbes as well as the determination
of the microbe's sensitivity to drug therapy. These scientific
advances will allow health care workers to diagnose and
treat patients more accurately and quickly.
NIH-supported researchers are developing
vaccines that are effective against many infectious agents,
including those considered to be bioterrorism threats,
with the intention of developing products that are safe
and effective in civilian populations of varying ages
and health status. Vaccines against pathogens are being
developed using both traditional and novel technologies.
Some novel technologies include the development of "DNA
vaccines", various vector vaccines, and innovative systems
for the rapid creation of vaccines against unfamiliar
or genetically altered pathogens; these technologies are
in various stages of development.
NIH therapeutics research focuses
on the development of new antimicrobials and antitoxins,
as well as the screening of existing antimicrobial agents
to determine whether they have activity against organisms
that might be employed by bioterrorists. Knowledge gained
from basic and applied research is helping to identify
additional targets for medications against agents of bioterrorism.
The design of therapeutic drugs active against known drug-resistant
variants of microbes, and the development of broad-spectrum
agents are also important NIH research priorities.
Together, these efforts create the
strong foundation from which the NIH carries out bioterrorism
research activities. Two cogent examples of this multifaceted
research approach are the specific NIH projects in the
areas of smallpox and anthrax.
is considered one of the most dangerous, potential biological
weapons because it is easily transmitted from person-to-person,
and very few people carry full immunity to the virus.
Historically, the mortality of smallpox infection has
been approximately 30 percent; those patients who recover
frequently have disfiguring scars.
research on smallpox focuses primarily on extending existing
vaccine stocks to increase the number of available doses,
and developing new vaccines and treatments for the entire
population, as well as diagnostic tools to detect the
At present, the approximately 15 million
doses of the traditionally employed and highly effective
"Dryvax" vaccine that have been stored since production
stopped in 1983 would not be enough to respond to a national
smallpox epidemic. In response to this shortage, NIAID
initiated a study last year to determine the feasibility
of expanding the use of the existing stores of the Dryvax
vaccine by dilution. In this study, investigators examined
and compared the skin and immune system responses of normal
unimmunized adult volunteers who were given undiluted
Dryvax vaccine, a 1:10 dilution (10 percent) of vaccine
or a 1:100 dilution (1 percent) of vaccine. The results
showed that the full-strength vaccine had maintained its
potency, and that 70 percent of people who received a
single dose of the 10-percent diluted vaccine developed
a sore followed by a scab at the injection site and antibodies
in their blood, strongly suggesting protection. The 1:100
dilution had an unacceptably low take rate.
Based on these findings, a larger
study is underway to determine the best strategy for optimal
use of available vaccine. This study, which will enroll
up to 684 people, is evaluating three different doses
(undiluted, 1:5, 1:10) of Dryvax. Researchers will study
the ability of the various vaccine formulations to stimulate
a scab, or "take," at the vaccination site and to produce
neutralizing antibodies in the blood. If participants
have not developed a scab in seven to nine days after
vaccination, they will be revaccinated with the same vaccine
dose they received the first time. By that strategy, researchers
hope to learn which vaccine dose given in a single injection
elicits the desirable response among the largest number
of people and whether "boosters" can increase the take
rate on a population basis.
also designing clinical protocols for testing of Dryvax
in previously immunized adults and in children. At the
same time, we are investigating the newer cell culture
based smallpox vaccines as well as alternative vaccination
strategies with the goal of designing safer and more effective
also supports long-established contracts that conduct
in vitro and in vivo screening of known
antiviral compounds to determine if they are effective
against viruses that are similar to smallpox (vaccinia
virus and cowpox virus). Compounds with promising in
vitro activity are further evaluated in animal models
of orthopoxvirus infection by both United States Army
Medical Research Institute of Infectious Diseases (USAMRIID)
and NIAID-supported investigators. To date, NIAID and
USAMRIID have screened approximately 500 compounds. The
drug cidofovir has been shown in multiple test systems
to have activity against all orthopoxviruses tested in
vitro and in vivo. NIAID submitted an Investigational
New Drug (IND) application for use of this drug as a backup
to vaccinia immune globulin (VIG) in our dilutional vaccine
studies and possibly for the emergency treatment of smallpox
should a bioterrorism attack occur.
collaborative activity that will accelerate the development
of new treatments and vaccines for smallpox is the recent
establishment of the "Orthopoxvirus Genomics and Bioinformatics
Resource Center." NIAID, the Defense Advanced Research
Projects Agency (DARPA), the Centers for Disease Control
and Prevention (CDC), USAMRIID and the American Type Culture
Collection have all contributed toward this Center, which
will conduct sequence and functional comparisons of genes
to provide insights for the selection of targets for the
design of antivirals and vaccines.
With regard to anthrax research, NIAID
has been collaborating with the Department of Defense
(DOD) to support the development of the next generation
of anthrax vaccines that may be more appropriate than
the current anthrax vaccine for use in the civilian population.
At present, we are currently planning Phase 1 safety and
immunogenicity trial for the USAMRIID recombinant protective
antigen (rPA), one of the leading anthrax vaccine candidates.
In addition, NIAID is utilizing its vaccine production
and support contractor, Science Applications International
Corporation (SAIC) to facilitate and expedite the development
of additional rPA vaccines.
NIAID is also exploring rapid diagnosis
of anthrax and the utility of available antimicrobial
or antitoxin therapies. Together with the Food and Drug
Administration (FDA), CDC, and USAMRIID, NIH is working
to prioritize and accelerate testing of existing antimicrobials
for use against anthrax. Last month, NIAID-supported investigators
published two studies in the scientific journal Nature
that help to explain how anthrax toxin destroys cells.
In the first study, researchers have identified the site
on the cell that binds the anthrax toxin and have developed
a compound that may disable it. Another group of investigators
has characterized the structure of a major component of
the anthrax toxin. The information gained through these
studies will likely hasten the development of new drugs
to treat anthrax.
In addition, the NIAID, through an
Inter-Agency Agreement with the Office of Naval Research,
has provided funds to help complete work on sequencing
the genome of B. anthracis. The information derived
from this genome-sequencing project should be of great
value in developing rapid diagnostic tests, as well as
new vaccines and antibiotics therapies against mutant
strains of B. anthracis.
Although the focus of national attention
has been on smallpox and anthrax, we must not overlook
other organisms of bioterrorism, including agents that
cause plague, tularemia, botulism, and viral hemorrhagic
fevers. NIH-supported research is yielding insights in
these areas. For example, intramural investigators at
NIAID's Dale and Betty Bumpers Vaccine Research Center
have developed a DNA vaccine that has protected monkeys
from infection with Ebola virus; this vaccine could soon
enter human trials.
Together with our many research partners,
NIH has made substantial progress in the research effort
that is critical to our Nation's fight against emerging
diseases, including those that are intentionally released
as agents of terrorism. In addition to previously mentioned
collaborations with other government agencies, NIAID maintains
important partnerships with industry that are essential
to the development of new technologies and treatments
in the arena of infectious diseases.
Much remains to be accomplished, however, and the challenges
posed by bioterrorism will require a sustained commitment
over the years to come. Within the next few weeks, NIH
will announce new initiatives for funding in Fiscal Year
2002 to provide the academic and industrial research communities
with an opportunity to propose studies targeting new approaches
to research on agents of bioterrorism. For example, we
will unveil an initiative entitled "Partnerships for Novel
Therapeutic, Diagnostic and Vector Control Strategies
in Infectious Diseases," which will involve substantive
involvement by a private sector partner and focus on areas
that are currently not a high priority or that may be
too financially risky for industry to pursue alone, but
are likely to have a high impact on public health. The
submission, review, and funding of these proposals will
be expedited in order to facilitate the rapid advance
of these important research endeavors. This information
is being made available to the public and the research
community through our website.
With a strong research base, talented
investigators throughout the country, and the availability
of powerful new research tools, we fully expect that our
basic and applied research programs will provide the essential
elements that will greatly enhance our defenses against
those who attempt to harm us with bioterrorism.
That concludes my testimony. I would be happy to respond
to any questions that you might have.
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revised: November 30, 2001