April 7, 2003
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 other "new" 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's Children's 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 NIAID will expand this capacity for research on emerging acute viral respiratory diseases, including pandemic influenza and SARS.
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, including interferons, 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.
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.
Last Revised: April 7, 2003