Mr. Chairman and Members of the Committee, thank you for the opportunity
to discuss the research activities of the National Institutes of Health
(NIH) that promise to help us better understand and counter the global
outbreak of Severe Acute Respiratory Syndrome, or SARS. I am pleased
to share this table with Dr. Julie Gerberding, the Director of our sister
agency, the Centers for Disease Control and Prevention (CDC), which
has done such an extraordinary job in responding to the evolving epidemic.
As Dr. Gerberding will discuss in some detail, SARS rapidly has moved
across the globe, becoming a worldwide health emergency that has resulted
in quarantines, travel warnings, and mounting economic damage. The global
tally of SARS cases has grown to more than 2,300 cases in only six weeks
since the apparent emergence of the disease. At this early stage of
the epidemic, it is impossible to predict whether SARS will become an
ongoing, major global health threat, or if the epidemic will spontaneously
burn out or be contained by public health measures. However, we must
be prepared for the worst-case scenario.
Dr. Gerberding and her CDC team, together with the World Health Organization
(WHO) and others, have done a magnificent job in identifying and tracking
this epidemic, illuminating the etiology and clinical features of SARS,
and providing the world with information about the epidemic in real
time. Complementing the efforts of the CDC and WHO, the National Institute
of Allergy and Infectious Diseases (NIAID), a component of NIH, also
has a significant role in the efforts against SARS, notably by rapidly
addressing the issues of vaccine development, drug screening, and clinical research.
As with Lyme disease, Hepatitis C, HIV/AIDS, Ebola, West Nile virus
and a host of diseases, the SARS outbreak has reminded us that the emergence
or reemergence of infectious diseases is a constant threat. As has been
the case with other emerging diseases, we anticipate that the strong
NIAID research base in disciplines such as microbiology, immunology
and infectious diseases will facilitate the development of interventions
such as diagnostics, therapies, and vaccines to help counter SARS.
As described by CDC and WHO, evidence is mounting, although not yet
definitive, that SARS is caused by a novel coronavirus that may have
crossed species from an animal to humans. This hypothesis is based on
the detection and isolation of coronaviruses from unrelated patients
from different countries, and on the finding that several SARS patients
have mounted an immunological response to coronavirus as they proceeded
from the acute illness to the recovery or convalescent stage. While
some questions remain for example, there is some evidence that a second
virus may contribute to the pathogenesis of SARS -- the strong evidence
for a causative role for a coronavirus justifies the ongoing development
of diagnostic tools, therapies and vaccines that target coronaviruses.
Coronaviruses are best known as one of the causes of the common cold,
which is generally a very benign condition, very rarely resulting in
life-threatening disease. The coronavirus that has been shown to be
associated with SARS is a new type of coronavirus that has not been
previously identified.
I would note that no evidence of genetic tampering of the virus implicated
in SARS has been detected, based on analyses of the mounting genomic
sequence data of the samples from SARS patients examined so far. As
even more extensive genomic sequence data become available for the SARS
virus, it will be possible to further distinguish natural origin from
the possibility that the SARS agent was created in a laboratory or even
as a bioweapon. Until then, we will keep our minds open to these possibilities,
however remote.
NIAID Research on SARS
NIAID maintains a longstanding commitment to conducting and supporting
research on emerging infectious diseases, such as SARS, with the goal
of improving global health. In carrying out its global health research
mission, the Institute supports a myriad of activities, including intramural
and extramural research, and collaborations with international agencies
and organizations. Since the first SARS reports, NIAID has worked rapidly
to identify opportunities for accelerating or expanding research to
improve the diagnosis, treatment, and prevention of SARS. These areas
include: Surveillance and epidemiology NIAID supports a long-standing
program for surveillance of influenza viruses in Hong Kong, led by Dr.
Robert Webster of St. Jude Childrens Research Hospital in Memphis. Dr.
Webster and his team in Hong Kong have collaborated with WHO, CDC and
others in helping to illuminate the SARS outbreaks in Asia. In addition,
at the request of WHO, NIAID assigned a staff epidemiologist to provide
epidemiologic and logistical assistance during the early stages of the epidemic.
Diagnostics
As discussed by Dr. Gerberding, significant progress has been made
by the CDC in developing a diagnostic test for SARS. As part of these
efforts, NIAID-sponsored researchers in Hong Kong also devised a diagnostic
test based on PCR technology as well as a diagnostic tool using the
immunofluorescence assay technique. In other research, the NIAID-funded
Respiratory Pathogens Research Unit (RPRU) at Baylor College of Medicine
has developed methods to detect known human coronaviruses using cell
culture and molecular diagnostic tools and can also assess the host
immune response to known coronavirus infections. In 2003 will expand
this capacity for research on emerging acute viral respiratory diseases,
including pandemic influenza and Vaccine Research.
As the SARS epidemic continues, it will be necessary to consider a
broad spectrum of vaccine approaches, as well as immunotherapy. NIAID
is supporting the rapid development of vaccines to prevent SARS through
both our extramural and intramural programs, including the NIAID Vaccine
Research Center. Initially, these efforts are focusing on the development
of an inactivated (or killed) virus vaccine. However, other approaches
will soon follow, including novel approaches such as vector-based and
recombinant vaccines, DNA-based vaccines and live attenuated vaccines,
as more knowledge about the cause of SARS and its etiology becomes available.
NIAID scientists have received samples of the SARS coronavirus from
CDC and have initiated efforts to develop a vaccine. Fortuitously, vaccines
against common veterinary coronaviruses are routinely used to prevent
serious diseases in young animals, such as a vaccine given to pigs to
prevent serious enteric coronavirus disease. These models could prove
useful as we develop vaccines to protect humans.
To further accelerate SARS vaccine research and development efforts,
NIAID is initiating contracts with companies, institutions and other
organizations who have relevant technologies, cell lines and containment
facilities; supporting the development of reagents needed for vaccine
development; and developing animal models such as mice and relevant
species of monkeys.
Therapeutics Research
As the nation began its focus on SARS, NIAID responded rapidly to a
request from CDC to evaluate candidate antiviral therapeutic agents
through a collaborative antiviral drug-screening project at the U.S.
Army Medical Research Institute of Infectious Diseases (USAMRIID). NIAID
also has initiated discussions with the pharmaceutical industry about
candidate antiviral drugs, and is reviewing a proposal for a clinical
trial of antiviral therapy to be conducted by investigators of the NIAID
Collaborative Antiviral Study Group and the NIH Clinical Center.
Clinical Research
Clinicians treating SARS patients have not yet identified treatment
strategies that consistently improve prognosis, beyond good intensive
and supportive care. Antibiotics do not work, a fact that is consistent
with SARS being a viral disease. However, some improvement has been
noted in certain patients treated with a combination of ribavirin and
corticosteroids, which are given together in an effort to simultaneously
block viral replication and modify the immune system reaction to the virus.
At the NIH Clinical Center in Bethesda, MD, and through the NIAID Collaborative
Antiviral Study Group, NIH is preparing to admit SARS patients for evaluation
and treatment, should this become necessary. This will be an opportunity
to evaluate the efficacy of antiviral and immune-based therapies in
patients with SARS. We also plan to evaluate approaches to improve management
of patients with severe forms of the disease, including the passive
transfer of antibodies from SARS patients who have recovered from the disease.
In addition to ensuring state-of-the-art treatment of potential patients,
our clinical experts will be able to study the clinical characteristics
of patients with SARS. We are particularly interested in answering key
questions about the disease mechanisms of SARS. For example, are acute
respiratory distress and mortality entirely caused by the presence of
virus, or could it be that the response of the immune system is causing
the severe outcomes in some patients? This is a central question to
address because it may open up an avenue for treatment in addition to
antiviral drugs.
Basic Research
NIAID currently is supporting 18 grants on coronavirus research. Also,
the study of patients, as well as specimens in NIAID laboratories, will
facilitate studies of the natural history of the SARS agent and its
potential animal reservoir, and help to illuminate the risk factors
and epidemiology of SARS. NIAID will support and conduct basic research
studies on the pathogenesis of the disease and viral replication mechanisms,
in order to identify targets for antiviral drugs, diagnostic tests and
vaccines. Finally, the Institute will support and conduct genomic sequencing,
proteomics and informatics of coronaviruses.
Of note, an existing NIAID animal model of a virus infection that causes
a disease in mice very similar to SARS has been identified. The relevance
of this animal model will be evaluated and may prove an important tool
for defining treatment approaches to SARS that involve modulation of
the immune system.
Infrastructure
A central concern when working with the SARS virus or SARS patients
is the availability of facilities with the required safety level for
the clinicians and staff, as well as for the community. Our ongoing
plans to develop high-level containment facilities will facilitate SARS
research, as well as planned studies of potential bioterror agents and
other emerging diseases.
Conclusion
Mr. Chairman, thank you again for allowing me to discuss our efforts
to address SARS. Despite ongoing research efforts and early successes,
we still have much to learn about the disease. As you have heard, NIAID-sponsored
coronavirus research, studies of other viral diseases, and clinical
research already have provided results that are relevant to our quest
for tools to detect, treat and prevent SARS. In the weeks and months
ahead, NIH will continue to collaborate with our sister agencies the
CDC and the Food and Drug Administration, as well as other relevant
agencies to accelerate and expand our research aimed at improving the
diagnosis, prevention, and treatment of SARS.
I would be pleased to answer your questions.