Pertussis Vaccine - Collaborations between NIH-supported scientists, vaccine manufacturers, and investigators around the world recently have resulted in a new class of vaccines for pertussis, or whooping cough, which each year claims 350,000 lives worldwide, primarily infants. The pertussis vaccine type that has been the "gold standard" for nearly 50 years is made from whole, killed pertussis-causing bacteria. It is extremely effective, but has been associated with adverse effects more frequently than any other vaccine in general use for infants. Many years of collaboration between NIH-supported basic scientists and the pharmaceutical industry have led to the development of so-called acellular pertussis vaccines that use only parts of pertussis bacteria instead of the whole organism. NIH-supported trials have demonstrated that three new acellular pertussis vaccines markedly reduce the frequency of side effects without diminishing the vaccines' effectiveness. Rotavirus Vaccine - NIH intramural scientists recently developed and patented the first vaccine against rotavirus, the cause of infections that annually result in an estimated 130 million cases of diarrhea in infants and children. Moderate to severe dehydration occurs in 18 million of these episodes, and more than 870,000 children world-wide die as a consequence. In the United States alone, rotaviral infections incur costs of $500 million annually in doctor visits and hospitalizations. The new vaccine protects against four different strains of human rotavirus. Clinical trials have shown the vaccine to safely achieve significant reductions in the incidence of rotavirus diarrhea. It is 80 percent protective against severe rotaviral disease and completely effective in preventing dehydrating illness. Routine childhood vaccination against rotavirus could quickly alleviate this major public health problem. Hemophilus influenzae type b Vaccine - The vaccine against Hemophilus influenzae type b (Hib) meningitis provides the means to completely eliminate this disease from the United States within the next few years. For years, this disease had devastated our children, affecting 15 to 20 thousand of them each year, almost as many as polio at its peak. Hib killed 10 percent and left one third deaf and another one third mentally retarded, making it this country's leading cause of acquired mental retardation. Fortunately, two NIH scientists were instrumental in developing a safe and effective vaccine which, together with three other licensed Hib vaccines, has reduced the incidence of Hib by 95 percent since their use began in 1988. With greater use across the country, we have the hope of completely eliminating Hib meningitis. societal benefits. For these reasons, prevention research is a high priority and spans the full range of biomedical and behavioral research. The latest technologies, such as protein engineering and recombinant vaccine development as well as social and behavioral sciences, are being put to good use in erecting effective barriers against disease and disability. Rising health care costs increase the importance of research to prevent disease and minimize the impact of illness and injury. New preventive strategies against disease involve investigations of emerging infections, as well as the prevention and treatment of drug and alcohol abuse. Vaccines against cancer and infectious diseases such as HIV, otitis media (earaches), herpes, chicken pox, pneumococcus, Shigella and Salmonella, are being studied. Prevention also entails the behavioral, genetic, and environmental aspects of risk assessment. The control of transmission of infectious disease by, for example, microbicide or behavioral changes, is an important aspect of prevention research. Prevention research across all stages of life includes reducing sudden infant death syndrome (SIDS) and early diagnosis of osteoporosis. In addition, bionutrition, including the genetic basis of eating disorders and pathological consequences of particular diets, has become an important area for study in prevention of disease. EMERGING INFECTIOUS DISEASES To ward off pathogenic microbes, we are critically dependent on research to identify infectious diseases and to provide improved drugs and new vaccines. Both basic and clinical research are key, as the speed with which we develop the new antibiotics, new vaccines, and effective treatments will depend upon our understanding of the human immune system and the ever-growing number of pathogens that threaten. human health. Research must also focus on the relationships and linkages among disease and climate, ecological change, population growth, and human behavior. Vaccines are our strongest form of preventive medicine. Scientists supported by the National Institutes of Health have developed new vaccines for pertussis, rotavirus, and Hemophilus influenzae type b. The latter vaccine provides the means to completely eliminate this disease from the United States in the next few years. Since Vice President Gore announced the President's policy directive on emerging infectious diseases (EID) in July 1996 (see vignette on Combatting Ebola Hemorrhagic Fever, Chapter 3), the National Science and Technology Council launched a number of new research initiatives. To expand EID research, for example, NIH has funded ten international EID training awards and provided funding to expand four ongoing research and training efforts related to EIDs. The VA and DOD are investing jointly in research on emerging pathogens. NASA is supporting an NIH effort to study emerging viral diseases using remote sensing, and the Centers for Disease Control and Prevention are cooperating with NIH on epidemiologic surveys. NIH also has initiated long-term programs to study hepatitis C, hantavirus, the infectious origins of gastric ulcers, and Lyme disease. NIH and DOD are cooperating on the synthesis and testing of a new drug against the Ebola virus. BETTER HEALTH THROUGH VACCINES New recombinant DNA tools, advanced gene transfer techniques, and monoclonal antibody production are greatly improving public vaccination efforts. Vaccines now in development will provide greater protection for our nation's children against a wide range of infections and will lead to reduced disease and lower health care costs. For example, development of a vaccine against otitis media is under way. Such a vaccine would benefit millions of American children who suffer from this often chronic disease, which is responsible for more than $3.5 billion worth of visits to doctors' offices, clinics, and emergency rooms annually. In response to a comprehensive evaluation of the NIH AIDS research program, NIH has established an AIDS Vaccine Research Committee, a highly distinguished group of outside advisors in immunology, virology, and vaccinology. The committee, chaired by Nobel Laureate David Baltimore, will address key scientific questions in vaccine development, including new vaccine designs, efforts to understand the mechanisms of protection in animal models, and potential new targets for vaccines. PREVENTING DISABILITY AMONG OLDER AMERICANS Preventive health care for older Americans has a high payoff. More than $108 billion is spent annually on longterm care for the elderly in the United States. Researchers are studying risk factors for disability, improving screening processes to identify at-risk populations, and designing and evaluating interventions specifically targeted to at-risk individuals. The research is paying off: •Three short tests of physical performance abilities can • Older persons with three selected risk factors • Research showed a 44 percent reduction in serious falls among older persons through the use of interventions focused on physical risk factors, such as bone fragility, muscle weakness, use of sedatives or multiple medications, and balance and walking problems. •Elderly patients who were cared for in a special hospital unit that focused on rehabilitation, prevention of disability, and preparation for the patient's return to home were significantly more able to perform basic activities of daily living and less likely to need institutionalized long-term care than individuals who these disorders have been difficult to discover. Research at the NIH Center for Inherited Disease Research will specialize in applying computer-based technology and robotics to conduct large-scale, rapid genetic analysis of these diseases, leading to the identification of the genes involved. Developments are currently under way to enable simultaneous analysis of thousands of DNA strands on a single silicon chip. These micro-machines greatly speed up research and lower its cost. CANCER GENETICS December 1996 marked the twenty-fifth anniversary of the war on cancer. Since 1971, scientists have discovered the causes of many cancers and have proven that cancer can be cured. Today, more than ten million of our family members, friends, neighbors and coworkers owe their lives to cancer research. Cancer survivors are alive today and enjoy a better quality of life because the years of research in prevention, diagnosis, and treatment methods have given doctors better information and more accurate tools. America's youth have received the greatest benefit from this country's investment in cancer research. For example, most cases of childhood leukemia are now curable. Death rates from children's cancers have declined by more than 62 percent. Cancer research has also brought about dramatic improvements in the survival rates for adults. The death rate for testicular cancer, for example, has declined 66 percent and five-year survival is now 95 percent. Today, most Hodgkin's disease patients can be cured. Gene-based therapies are one class of exciting new approaches under investigation in cancer treatment. These methods are designed to augment the immune system's response to cancer or to boost the effectiveness of chemotherapeutic agents. They may involve administration of genes for immune factors, either in the patient or in cells taken from the patient and then returned. Another method is to give the patient genes that will increase the tumor's sensitivity to an anticancer drug, thus reducing harmful side effects on normal cells. Yet another technique involves the use of drug-resistance genes that protect the vulnerable bone marrow from highly toxic chemotherapy. Important goals for the future include the development of better viral vectors for delivering genes to their intended target cells and regulating production of the introduced genes' protein products. A new project of the National Cancer Institute (NCI) provides another exciting example of the application of this technology to the understanding of disease. The Cancer Genome Anatomy Project seeks to define all the genes that play a critical role in the development of cancer. The project will develop high volume, cost effective technologies to analyze the molecular mechanics of cancer cells and put those technologies in the hands of clinical researchers. Coupling these technologies with clinical investigation will provide a better understanding of the basis of disease, as well its detection, diagnosis, prognosis, development of treatments, and selection of therapy. Breast Cancer In 1995, in the United States alone, 182,000 new cases of breast cancer were diagnosed. Forty-six thousand women died from the disease. Health care costs of breast cancer exceed $12 billion per year. In an extension of the exciting discovery in 1994 of a gene that confers susceptibility to breast and ovarian cancer, NIH scientists and collaborators discovered a specific mutation in the BRCA-1 gene in nearly 1 percent of samples of blood from women of Ashkenazi Jewish descent. This finding identifies a particular subgroup of the population that may benefit from genetic testing for the BRCA-1 mutation. Epidemiologists have hypothesized that this mutation may account for as much as 16 percent of breast and 39 percent of ovarian cancers among Ashkenazi Jewish women age 50 and under. Studies of families with inherited alterations of BRCA-1 suggest that more than half of the women who inherit mutations in BRCA-1 will be diagnosed with breast cancers by age 50, and more than 85 percent will have breast cancer by age 70. OBESITY In the United States, obesity is second only to tobacco as a risk factor for disease and accounts for about 300,000 deaths per year and an economic cost of $50-$100 billion. Obese individuals suffer increased risk for numerous chronic diseases, such as diabetes mellitus, cardiovascular disease, hypertension, gallbladder disease, and certain cancers. Fortunately, opportunities to attack obesity at the molecular level have multiplied. NIH-supported scientists have made important new discoveries regarding the obese (ob) gene, its protein product (leptin), its receptors, and its interactions with other regulators of energy expenditure and food intake. |