NATIONAL INSTITUTES OF HEALTH

The National Institutes of Health (NIH) is the biomedical research agency of the U.S. federal government. Located in Bethesda, Maryland, a suburb of Washington, DC, the NIH funds intramural (federal employee) scientists and extramural (outside the federal government) researchers across the country. Eighty percent of the NIH budget goes to grants to outside universities and laboratories. Research conducted at the NIH or with NIH funds leads to a more complete understanding of human health and to developing preventions, cures, and therapies for disease. At the same time, the agency has been forced to address and respond to ethical questions regarding research subjects, research topics, and scientific conflicts of interest.

From the Marine Hospital Service to the Hygiene Laboratory

In 1798 President John Adams signed legislation that started the United States on a long road of funding health-related activities by creating a Marine Hospital Service (MHS), an agency that would fund hospitals in ports to care for military personnel when they fell sick at sea. However the U.S. government did not support health-related research for much of the nineteenth century.

Widespread acceptance of the germ theory in the 1870s led to an increase in the number of American scientists doing research on disease. The basic idea that one specific germ caused one specific disease led to an explosion of new studies on microbes, immunity, and vaccines. Scientists began to trace diseases back to a particular vector such as water, milk, insects, or healthy human carriers. The government began to organize and enforce quarantines to curb epidemics—and such measures worked. Scientists soon identified the bacteria that caused diphtheria, tuberculosis, typhoid fever, anthrax, and malaria.

In the 1880s, the government decided to expand the role of the MHS to include bacteriological research. A laboratory was set up at the MHS facilities in Staten Island, New York, and Joseph Kinyoun was appointed to run it, since he was one of the few MHS officers who had studied the new science of bacteriology. Kinyoun called his facility a laboratory of hygiene and it soon became known as the Hygienic Laboratory. Kinyoun's first paper described his methods for making a positive diagnosis of cholera using his microscope and bacteriological methods.

In 1891 the laboratory moved to a more prestigious government location: near the U.S. Capitol Building in Washington, DC. Kinyoun and his associates began to manufacture vaccines and antitoxins (known collectively as biologics) for diphtheria, rabies, and smallpox. After a tragedy caused by contaminated diphtheria antitoxin in St. Louis, Congress passed the 1902 Biologics Control Act, putting the Hygienic Laboratory in control of regulating biologics for the entire country.

In 1902 Congress expanded the Marine Hospital Service to the broader Public Health and Marine Hospital Service and reorganized the laboratory. The four new divisions were Pathology and Bacteriology, Zoology, Chemistry, and Pharmacology. Ph.D.s were hired alongside the M.D.s, introducing new scientific techniques and expertise. In 1912 the name Marine Hospital Service was dropped entirely. Activities of the newly conceived laboratory included exploring noncontagious diseases and conducting studies of dairies, pollution, and water filtration systems to identify causes for disease. Scientists showed that their research could assist public health officials in preventing epidemics and keeping the public safe.

Epidemiology became an important function of the Hygienic Laboratory in the early twentieth century. Scientists would be dispatched to a location where there was an outbreak of a disease such as yellow fever or typhoid. They would investigate the cause of the disease by finding the vector that passed it along or identifying problems of diet or pollution. Joseph Goldberger, for example, traveled across the South for many years doing studies on populations with outbreaks of pellagra. By closely observing the people who had the disease, experimenting with different diets, and exhaustively searching for possible causes among the populations of small towns, institutions, orphanages, and prisons, he correctly identified the disease as a dietary deficiency, rather than a contagious disease. Goldberger's discovery eventually led to the elimination of pellagra as a dangerous disease that once plagued an entire region.

The staff of the Hygienic Laboratory grew. Rocky Mountain spotted fever studies spawned a new outpost in Montana to better study the insect vector in that region. While the Pathology and Bacteriology division researched diseases such as typhoid fever, the Zoology division studied a new species of hookworm known to cause disease and the Chemistry division studied the role of stomach acid and the chemistry of blood. The Pharmacology division studied toxicity of alcohols and the effect of certain drugs on blood pressure.

NIH: 1930s to 1950s

In 1930 Congress approved more funding for a new building and expanded the role of the Hygienic Laboratory—renamed the National Institute of Health by Senator Joseph Ransdell—to fund scientists in new fields such as the study of chemicals used in warfare. As the Great Depression further eroded private support of scientific research, scientists increasingly looked for help from the federal government. The Ransdell Act of 1930 ushered in a new era of expanded government support for scientific research.

Cancer became the first disease to generate enough public panic to build support for legislation funding scientific research. In 1937 every senator in Congress cosponsored a bill creating the National Cancer Institute (NCI), which would (in 1944) become a subset of the NIH. The 1937 bill was important for another reason: It authorized the NCI to award grants and fellowships to outside scientists conducting research. This granting (extramural) program would become a fundamental part of the NIH's work.

With more responsibilities came the demand for more space. In 1935 the government accepted a gift of land from suburban estate owners Luke and Helen Wilson. The original plan was to use the land for the growing number of animals used in research, but by 1941 all the scientists had packed up their laboratories and joined the animals in a newly built complex of six brick buildings.

During World War II NIH scientists studied many problems among workers in the war-related industries in the United States. For example, they studied the levels of toxicity incurred by people working in industries such as synthetic rubber, ships, tanks, munitions, and airplanes. Disease research focused on malaria, yellow fever, and typhus, all of which proved devastating to the troops abroad. NIH scientists also studied the oxygen needs of pilots at certain altitudes.

In 1944 Surgeon General Thomas Parran and NIH Director Rolla Dyer helped pass a new law, the Public Health Service (PHS) Act, which revitalized the NIH. The act authorized more granting authority to the NIH and also allowed for spending on clinical research. Additionally the NIH was required to prepare public materials to inform the general public about its research and how that research affected people's health.

The next decades were a period of rapid growth for the NIH. Based on the success of the National Cancer Institute, many of the new institutes focused on the study and cure of certain diseases. During World War II many recruits were deemed unfit for service due to poor mental health or poor dental health, leading to the creation of new institutes to ease the effect of these problems in the population. These included the National Heart Institute, the National Institute on Mental Health, and the National Institute of Dental Research.

In 1953 the promise of clinical research was realized in the NIH Clinical Center, then the largest research hospital in the world with 540 beds. The special design of the Clinical Center ensured that the scientists and physicians kept in close contact while studying the effects of certain drugs or therapies on patients. Doctors referred many of the patients to the Clinical Center from all over the country. Other patients were normal volunteers, whose participation in studies produced baseline information about how healthy people reacted to proposed therapies. This data could then be compared with that from ill patients.

The clinical center was opened in the shadow of Nazi medical experiments. Its initial ethics rules, guided by the Nuremburg code, mandated informed consent from the human subjects of research and instituted an internal review process. In 1974, after the abuses of the Tuskegee syphilis study were made public, congressional action required the creation of Institutional Review Boards (IRBs) to oversee human research projects and an office of protection from research risks at NIH to oversee the IRBs.

In the decades after World War II, the proliferation of institutes—most of them still linked to a particular disease or body part—brought hundreds and then thousands of scientists, laboratory technicians, and support staff to the Bethesda campus, which also grew to accommodate more buildings.

NIH: 1960s to 2000s

Virus research was one major area of study at the NIH in the 1950s and 1960s. Developing new ways to grow and identify viruses, scientists identified dozens of new virus strains, leading to better and more effective ideas for curbing outbreaks.

One major line of research that has carried through in dozens of NIH laboratories in the second half of the twentieth century is genetics. In the late 1950s and early 1960s, scientists working with Marshall Nirenberg deciphered the genetic code. Building on this basic research, researchers in the 1960s and early 1970s learned how to cut and recombine DNA. In the 1980s the Human Genome Project was launched with the goal of charting the human genome, a goal that was reached in 2003 by scientists at the National Human Genome Research Institute. NIH scientists have also been leaders in experimental clinical research such as gene therapy.

In the 1970s, fields such as genetics research advanced rapidly because of new molecular biology techniques and instrumentation. The scientific competition that resulted also led to misconduct by some scientists. Beginning in the early 1980s, NIH led investigations into this issue. It also sponsored studies on how to ensure research integrity and programs to incorporate ethics training in the graduate education of scientists.

Research on chronic disease has been a mainstay of NIH research, from the earliest days of cancer and heart research to diseases such as diabetes, arthritis, and drug and alcohol addiction. A long-term NIH-funded study in Framingham, Massachusetts, provided evidence about heart health that has led to major education campaigns about the importance of exercise, low-fat eating, and smoking cessation. Dental research led to the mass fluoridation of water as it was shown to reduce the number of dental caries in children. In the 1980s infectious disease again took center stage when NIH researchers began studying AIDS.

In the 1990s the NIH continued to expand. New institutes funded studies of the aging population and the effects of nursing on patient care. Thousands of NIH scientists conduct research on the main campus in Bethesda, and at outposts such as the National Institute of Environmental Health Research in North Carolina and the Rocky Mountain Laboratory in Montana. In 1998 Congress voted to double the NIH budget over five years, and this money funded scientists all over the country and even around the world.

The NIH is proud to claim five Nobel Prize winners who did their major work on the Bethesda campus. In addition, dozens of members of the National Academy of Sciences have worked at the NIH. Over 100 scientists based at other institutions won the Nobel Prize based on research conducted with NIH funding in fields as varied as chemistry, physiology, medicine, and economics.

Several centers founded in the 1980s and 1990s complement the basic science at the NIH. For example, the Center on Research in Women's Health tracks the inclusion of women in clinical trials of drugs and disease therapies, and the Office of Technology Transfer encourages partnerships between scientists and industry. The National Center on Minority Health and Health Disparities monitors the NIH and works to eliminate health disparities. The National Center for Research Resources helps link scientists with the resources they need to make their projects work. These and other components of the NIH help ensure that the mandate to inform and protect the public from disease is carried out.

Ethics and Politics

In 1977, the NIH added a bioethicist to its staff. In 1995, bioethics was expanded to an entire program that supports training of new bioethicists and conducts research that seeks to inform public policy in health research. Though many argue that disease knows no politics, the NIH has had to deal with many issues that have divided bioethicists and the agency's supporters along political lines. Certain choices about which diseases to study and which patients to admit (such as AIDS patients in the 1980s) aroused controversy. Stem cell research worried many Americans and Congress members in the late 1990s and at the turn of the twenty-first century. New allegations in 2003 about NIH scientists accepting funding from pharmaceutical companies led to congressional calls for stricter rules about consulting and stock ownership. The regulations, similar to those imposed on scientists at regulartory agencies, sharply curtailed participation by NIH scientists on boards, committees, and participation in professional associations as well as their ownership of health-related stocks. In 2005, the new rules led to intense debate among NIH staff and scientists, who feared that they would result in driving top people away from federal service. Though for the most part scientists can work quietly in their laboratories without worrying about politics, institute directors must testify before Congress about how they are spending taxpayers' money. In 2005 with 27 institutes and centers and an annual budget of $27.9 billion, the NIH would be barely recognizable to Joseph Kinyoun, its first director.

SARAH A. LEAVITT

SEE ALSO Complementary and Alternative Medicine;Health and Disease;National Academies;Research Integrity.

BIBLIOGRAPHY

Harden, Victoria A. (1986). Inventing the NIH: Federal Biomedical Research Policy, 1887–1937. Baltimore: Johns Hopkins University Press. This volume describes the research conducted at the Hygeinic Laboratory and the expansion of its research program in the early-twentieth century before the NIH moved to Bethesda.

Kraut, Alan M. (2003). Goldberger's War: The Life and Work of a Public Health Crusader. New York: Hill and Wang. This engaging work explores the epidemiological work of Dr. Joseph Goldberger, a PHS scientist who solved the mystery of the cause of pellagra in the early twentieth century. The book outlines the policies and research goals of the early Hygeinic Laboratory scientists in Washington, DC.

Park, Buhm Soon. (2003). "The Development of the Intramural Research Program at the National Institutes of Health After World War II." Perspectives in Biology and Medicine 46(3): 383–402. This article outlines the research plans of the NIH as it grew astronomically in the decades after World War II. New goals are examined, the work of particular scientists is explored, and the overall mission of the NIH in this period is explained.

Hannaway, Caroline; Victoria Harden; and John Parascandola, eds. (1995). AIDS and the Public Debate: Historical and Contemporary Perspectives. Amsterdam and Washington, DC: IOS Press. This edited volume includes an essay by former Surgeon General C. Everett Koop in which he describes his positions on AIDS-related sexual education topics in the 1980s. The volume is an important addition to the story of how U.S. scientific and medical communities responded to the AIDS epidemic and how the NIH was influential in the early years of research and clinical studies.

INTERNET RESOURCE

National Institutes of Health. Available from www.history.nih.gov. This web site links visitors to a brief illustrated history of the NIH, along with more specialized web exhibits on certain research initiatives, such as genetics research, particular individual scientists such as Martin Rodbell and Marshall Nirenberg, and particular scientific achievements at the NIH. The site also provides bibliographies, copies of unpublished and out-of-print sources on NIH history, and much more.

NATIONAL INSTITUTES OF HEALTH

The National Institutes of Health (NIH) is the principal federal agency that supports and conducts biomedical research on the prevention and treatment of disease. It is the center of biomedical research in the United States and the foremost medical research enterprise in the world, with a budget in 2001 of $20.3 billion. An agency of the U.S. Public Health Service, it is a part of the U.S. Department of Health and Human Services. There are twenty-seven institutes and centers that comprise the National Institutes of Health, and the research supported by these institutes ranges from basic molecular and genomic biology to translational and applied studies involving individuals and large populations. Training for careers in biomedical research is also an important part of the NIH mission, as is the dissemination of information from this research to the public, to health providers, and to scientists.

HISTORY OF NIH

The history of NIH reflects an interweaving of the disciplines of public health, medicine, and basic biology, with a changing emphasis among these areas as health science progressed. The NIH had its origins in the Laboratory of Hygiene, which was created in 1887 to research cholera and other infectious diseases. The laboratory was an out-growth of the Marine Hospital Service created in 1798 and, in turn, became the Public Health Service in 1912. Early activities focused on infectious and communicable diseases brought to the United States on incoming ships, and on the prevention of epidemics of yellow fever and cholera. In 1914, Dr. Joseph Goldberger described his findings that pellagra was a nutritional deficiency disease, rather than an infectious disease, and could be prevented by appropriate diet. This discovery marked a shift from infectious disease investigation. Research on the importance of nutrition in disease causation was fostered by this discovery, and the essential nature of vitamins in health followed.

The modern era of NIH began in 1930 with the redesignation of the Hygienic Laboratory as the National Institute of Health. In 1935, 45 acres of land in Bethesda, Maryland, were donated for the use of the National Institute of Health. Additional gifts of land were made and the buildings and grounds on the current site and were dedicated in 1940.

The National Cancer Institute Act was passed in 1938, and the first awards for research fellowships were made the following year. Laboratories at NIH were important in improving prevention and medical care during World War II. The contributions of science to the war effort provided a compelling rationale for the remarkable investment in biomedical research that followed during the second half of the twentieth century.

The Public Health Service Act of 1944 provided the legislative authority for post–World War II research programs and made the National Cancer Institute a part of NIH. In 1948, the National Heart Institute was authorized, and the name of NIH officially became the National Institutes of Health. The research emphasis shifted to investigation of basic biology and biochemistry and the disorders of biology that lead to disease. Prevention and treatment of diseases have been based largely on understanding the fundamental alterations in biology following World War II. Support for research conducted at colleges and universities also increased with an expanding budget. Other institutes and centers have been authorized and totaled twenty-seven in 2001. A clinical center on the Bethesda campus was dedicated in 1953 as the principal on-campus or intramural resource for clinical research. This facility combines patient facilities (inpatient and outpatient) with laboratories to foster integration of research from patient to laboratory.

During the second half of the twentieth century, the breadth and complexity of biomedical research activities conducted at NIH and supported at non-NIH sites increased. From 1950 onward, research emphasis shifted to chronic diseases, which had assumed epidemic proportions in the United States and other industrialized countries. Basic levels of molecular biology and genomics were increasingly probed. This led to an important benchmark at the turn of the millennium—the publication of the human genome map. Information on the inherited susceptibility and the interplay between genetic and environmental factors will eventually provide insights that will be translated into practical research.

Studies of large populations, like the Framingham Heart Study, have also been initiated by NIH to delineate risks for disease. Similarly, large interventional trials have tested effective means of preventing and managing these risks. These investigations were an outgrowth of an improved understanding of disease causation and the need to extend these findings to patients and populations. The growth of knowledge has been exponential, and the investment in biomedical research has produced a remarkable return to the public in improved health and increased longevity. Political support for the NIH budget has been consistent and bipartisan, reflecting broad public-interest support and confidence in the benefits of health research.

SUPPORT OF RESEARCH

Research activities are conducted in the laboratories of NIH by intramural scientists and are further supported through extramural grants and contracts at 2,570 academic and research facilities in the United States and worldwide. The NIH laboratories and clinical facilities are located principally in Bethesda, Maryland, with additional laboratories located elsewhere in Maryland and in Montana. Intramural research accounts for only about 10 percent of the budget of NIH. The overwhelming majority of funds thus support research being conducted at extramural sites. These extramural research studies are supported by grants and contracts awarded to nonfederal scientists working in universities, medical schools, hospitals, and research institutions. In 2000, there were over 37,000 grants and contracts supporting research and over 16,000 grants supporting research training.

Both intramural and extramural research undergoes rigorous scientific review before being funded, and oversight continues during the course of the work. Investigators who want to conduct research prepare an application describing the proposed work. This application can be initiated by the investigator, or it can be submitted in response to an NIH-initiated solicitation. Grants and contracts to non-NIH institutions and scientists are awarded after review and evaluation by panels of scientists expert in the particular research area for which support is requested. These proposals are reviewed and scored for scientific merit and relevance.

The initial scientific review by scientific peers is followed with review by an advisory council of senior scientists representing the institute or center involved, and this council is charged with over-seeing the development of a balanced portfolio of sponsored research. The grants and contracts are funded by the institutes and centers from funds appropriated to them by Congress. This review by panels of nongovernmental scientific peers (the peer-review system) has been fundamental to the evaluation and support of meritorious research and to sound investment of public funds in research. The process of peer review is now used by many other governmental and nongovernmental organizations in the United States and internationally. The researchers report on progress during the conduct of the project and, importantly, report their results in journals and meetings, making the findings available to other investigators and to the public.

ORGANIZATION AND SCOPE OF NIH RESEARCH

The NIH supports and conducts research at all levels of scientific inquiry, from molecular biology through clinical research on individuals, to the study of large groups and communities. Support for training is provided at the levels of predoctoral, postdoctoral, and established investigators. Training is supported for all levels of scientific study. The institutes and centers typically support research and research training related to a specific condition (e.g., cancer, heart disease) or phase of life (e.g., child health and human development, aging) or for cross-cutting issues (e.g., health disparities, complementary and alternative medicine). Some centers are engaged in scientific review or support of research resources.

The development of the institutes has followed the evolution of public and Congressional interest in diseases and health issues. There is now a belief that research should be the foundation for health policy, medical care, and public health action. The orientation by condition or phase of life has derived from public and Congressional advocacy related to medical and public health issues. One strength of this organizational structure is the integration of basic scientists with clinical researchers in the investigation of diseases.

This vertical integration allows scientists to unite basic biology with clinical and public health science and to promote a translation of scientific advances to human clinical studies. This integration occurs in both intramural and extramural research programs, and both clinical and public health applications benefit from this orientation. Clinical research flourishes with the integration of basic research, and this has influenced medical training and specialty emphasis. Each institute or center supports the full spectrum of research, with a few exceptions.

The vertical organizational structure of the NIH requires special efforts to integrate research across the institutes at each scientific level—a horizontal integration. The commonalities of basic biologic mechanisms compel collaboration among scientists who might be studying, for example, the biology mechanisms involved in cancer or heart disease. Similarly, there are joint risks for conditions such as cancer and heart disease and this requires collaborative study of the risks to exposed populations. During the 1990s, the institutes emphasized cross-institute and trans-NIH research to afford an integration of populational research across institutes. To foster this integration, several programmatic offices within the Office of the NIH Director have been developed. The Office of Disease Prevention and the Office of Behavioral and Social Sciences Research are examples. These offices work with the institutes to develop crosscutting research in the areas of prevention and behavioral research, respectively, and to coordinate activities with other federal agencies and the private sector.

Examples of the vertical and horizontal integrations illustrate how this structure advances knowledge. The mapping of the human genome and discovery of specific genes related to particular diseases afford an opportunity to identify individuals at risk for disease and to develop approaches that might modify this risk and prevent disease. Importantly, the interplay between genetic and environmental risk can be determined and appropriate interventions developed. Variations of BRCA-1 and BRCA-2 genes were found in studies of families having a high risk of breast cancer, for example. Subsequent population studies have disclosed the prevalence and penetrance of these genes in more general populations and have provided realistic estimates of when to screen for the genetic variation. The abnormality encoded by these genes is being investigated and could lead to behavioral interventions to modify the risk of breast cancer.

Prevention research exemplifies cross-institute collaboration. Several personal and environmental risks affect development of more than one disease, and there may be beneficial as well as adverse effects. The use of hormonal replacement by menopausal women can have beneficial effects on cardiovascular disease, osteoporosis, and mental acuity, in addition to the aesthetic effects for which they are commonly taken. However, this therapy also poses risks for breast cancer and cancer of the uterus. To quantify the benefits and risks of hormonal replacement therapy for this range of clinical conditions, a large clinical trial is in progress utilizing the scientific expertise of several institutes and dependant on scientists at academic institutions with a range of specialty expertise in the conditions being studied. The planning, conduct, and monitoring of this large trial has required the participation of epidemiologists, biostatisticians, clinical trialists, and community organizers.

A description of the institutes and offices, their missions, and recent accomplishments are available at the NIH web site at http://www.nih.gov/. A list of all currently funded grants and contracts is available at http://www-commons.cit.nih.gov/crisp/, including an abstract describing the research project or program. A special web site containing all NIH-supported clinical trials is available at http://clinicaltrials.gov/. This site provides information to patients and referring physicians regarding available clinical trials.

William R. Harlan

(see also: Centers for Disease Control and Prevention; Healthy People 2010 )

Bibliography

Mullan, F. (1989). Plagues and Politics: The Story of the United States Public Health Service. New York: Basic Books.

National Institutes of Health. NIH Almanac. Washington, DC: U.S. Department of Health and Human Services. Published annually. Available online at http://www.nih.gov/about/almanac/index.html.

Shorter, E. (1987). The Health Century. New York: Doubleday.

Swain, D. C. (1962). "The Rise of a Research Empire: NIH, 1930–1950." Science 138:1233–1237.

National Institutes of Health (NIH)

The U.S. National Institutes of Health (NIH) are charged with the vital mission of uncovering new knowledge that will lead to better health for everyone. To carry out this ambitious task, the NIH has become the largest agency for biomedical research in the world. It consists of twenty-seven separate institutes and centers and has a multibillion-dollar budget. However, it did not start out this way.

History of the National Institutes of Health

In 1887, the NIH began in Staten Island, New York, as a one-room federal laboratory within the Marine Hospital Service (MHS). At the time, it was called the Laboratory of Hygiene . The MHS was responsible for preventing the spread of infectious disease in the United States. For example, the staff at the MHS examined passengers on arriving ships for signs of communicable diseases such as cholera and yellow fever. By 1891, the federal government required the MHS to take on the additional responsibilities of developing and testing vaccines . That year, the service was relocated to Washington, D.C., and renamed the Hygienic Laboratory.

In 1902, Congress passed the Biologics Control Act to regulate vaccines sold in the U.S. This resulted in the Hygienic Laboratory adding divisions in chemistry, pharmacology, and zoology, all on a meager annual budget of $50,000. After ten years, this enterprise, now called the U.S. Public Health Service (PHS), was further authorized to study chronic diseases (e.g., heart disease , diabetes , and cancer ) and infectious diseases (e.g., tuberculosis , influenza, and malaria ). Despite working with limited funds, its investigators made several remarkable medical discoveries during this period. For example, in 1920, Joseph Goldberger discovered that pellagra, a skin disease widely considered to be infectious, was in fact the result of a vitamin deficiency that could be prevented by proper nutrition .

In 1930, the Hygienic Laboratory became the National Institutes of Health (NIH), and by 1938 the unit had moved to a privately donated estate in Bethesda, Maryland. Today, this is the primary home of the National Institutes of Health.

Pursuing the Mission of NIH

The activities of the NIH are overseen by the Public Health Service, which, in turn, is directed by the U.S. Department of Health and Human Services. However, the mission, goal, and activities of NIH distinguish it as a unique federation of biomedical research institutes. In pursuit of its broader mission, the specific goal of the NIH is to acquire biomedical knowledge that will enable researchers and practitioners to prevent, control, detect, and treat disease and disability. To achieve this goal, the NIH directs a number of programs and activities, including: (1) conducting research at the facility; (2) supporting scientific explorations of investigators in other settings (e.g., universities, medical schools, clinical centers) nationwide and internationally; (3) providing training for researchers; and (4) fostering the dissemination of medical information. The Office of the Director (OD) sets policy for planning, managing, and coordinating these programs and activities.

Within the OD is the Office of Legislative Policy and Analysis (OLPA). OLPA is responsible for making sure that the results of all of this research inform public policy and public health laws. To this end, the OLPA supervises legislative analysis and policy development, and also acts as a liaison between the NIH and Congress. As a result of the OLPA's participation in congressional hearings, for example, the Dietary Supplement Health and Education Act (DSHEA) was authorized in 1993. Consequently, the NIH established the Office of Dietary Supplements to conduct and coordinate research relating to dietary supplements and their impact on the health of the public.

The Institutes and Centers

To support its mission, the NIH has developed into a broad and complex federation consisting of a total of twenty institutes and seven centers. Each institute and center has its own medical or public health focus with well-defined priorities. For example, some institutes concentrate on a particular disease area (e.g., cancer, diabetes) whereas others support biomedical research (e.g., promoting diversity, providing medical resources).

One of the NIH's institutes is the famous U.S. National Library of Medicine (NLM), the world's largest medical library, holding nearly six million items, such as books, professional journals (e.g., Science and Nature ), and photographs. A plethora of resources and search engines, including PubMed and MEDLINEplus, provide access to these materials through the World Wide Web.

In general, the institutes' research priorities are shaped by two things: (1) epidemiological assessments (i.e., studies of the distribution and determinants of diseases and injuries in populations), and (2) political pressure. In some cases, political concerns have affected plans for specific research directions regardless of the results of epidemiological assessments. For example, a wide variety of research supports the idea that stem cells (undifferentiated cells taken from human embryos) have great potential to reduce the burden of illness (stem cells can be used to create other body cells, such as blood cells, or to regenerate tissue, bone, and muscle). However, despite the potential value of these applications, political concerns have threatened to end funding for this kind of research. On August, 9, 2001, President George W. Bush announced his decision to allow federal funds to support research on existing human embryonic stem cell lines under certain limited conditions.

Human Subjects: Protection and Ethics

Because much of the research supported by the NIH is conducted on human subjects, the NIH has several offices and programs in place to protect participants and address bioethical research issues. For example, to protect the rights and welfare of human subjects, the NIH has established at least fourteen separate Institutional Review Boards (IRBs). IRB committee members must review, and approve, all human-subject research activities prior to, and throughout, a study. Each principal investigator (the scientist in charge of directing a research project) must prove to the IRB that all of their human subjects provided informed consent before participating in study procedures. In addition, researchers must ensure the privacy of their participants is protected and their data are kept confidential.

Accomplishments of the NIH

The NIH supports thousands of research projects every year. A small sample of the accomplishments from 2003 includes the following:

• The Human Genome Project—an ambitious international effort to identify the 30,000 genes in human DNA and determine the sequences of the three billion chemical base pairs that make up human DNA—was completed two years ahead of schedule. The data was made freely available to scientists around the world.
• New guidelines were published for the prevention, detection, and treatment of high blood pressure.
• A new Ebola vaccine proved successful in monkeys, with human trials to follow.
• The drug letrozol was shown to reduce recurrence of breast cancer.
• The serotonin transporter gene was discovered to influence the onset and severity of depression.
• Research showed that heart attack symptoms in women differ from those in men, which may help women and doctors identify the onset of an attack earlier.
• Scientists found that the levels of two proteins, beta-amyloid and tau, distinguish Alzheimer's patients from controls. This discovery may lead to the development of predictive and diagnostic tools.
• Combined estrogen and progestin therapy was found to increase the risk of dementia.
• Scientists discovered that a greater than usual number of copies of the a-synuclein gene may cause Parkinson's disease.
• A new West Nile Virus vaccine was shown to be effective in monkeys.
• An international research team found that using cloth to filter water in poor countries reduced the incidence of cholera by half.

—Paula Kepos

In addition to offices that protect research participants, the NIH contains a number of offices that address ethical concerns and appraise the potential social consequences of scientific pursuits. For example, the Office of Science Policy (OSP) advises the NIH director on policy issues that affect the research community. In addition, OSP coordinates the Trans-NIH Bioethics Committee (T-NBC), composed of scientists, ethicists, and IRB members. This group is explicitly responsible for developing policies and considering the ethical, legal, and social implications of NIH-funded research.

Funding Research Projects

The NIH's important role in health and medical research and training is reflected in a yearly budget of 23 billion dollars (as of fiscal year 2002), a sum generated almost entirely through taxes. Today, the NIH uses these funds to support over thirty thousand research projects conducted on the main campus (intramural) and away from campus (extramural) at universities, medical schools, and independent research institutions.

Although the intramural research conducted at the NIH is important, nearly 80 percent of the NIH's budget is spent on extramural grants to investigators and research institutions throughout the nation and the world. The grants program seeks to stimulate the discovery of biomedical knowledge by encouraging qualified scientists to participate in particular types of research. In addition, research grants and contracts guarantee that facilities, equipment, and human resources are available to conduct research.

Research and Biomedical Advances

Nationwide and internationally, over fifty thousand researchers have been awarded grants to conduct their studies away from NIH's main campus. Together, these researchers have made more scientific breakthroughs than could be listed in this book. Some noteworthy examples, however, include: (1) the discovery that antiretroviral drugs could prevent transmission of the HIV virus from mother to infant, (2) demonstrating that weight loss and restriction of dietary salt reduce the need for blood pressure-lowering drugs, (3) confirming that tight control of blood glucose (sugar) may help people living with diabetes prevent complications such as blindness, and (4) identifying leptin (a product of the "obesity " gene) and suggesting how it might be used to combat obesity in humans. A number of extramural investigators have also been honored with the Nobel Prize for their significant contributions to biomedical science. For example, the 1985 Nobel Prize in Physiology or Medicine was awarded jointly to Drs. Michael S. Brown and Joseph L. Goldstein for their discoveries concerning the regulation of cholesterol metabolism and its role in heart disease.

In addition to this work, research scientists, physicians, dentists, veterinarians, and nurses conduct more than two thousand intramural projects on the NIH campus. Several of these investigators have also received international attention for their discoveries. Currently, three Nobel laureates work at the NIH: Dr. Marshall W. Nirenberg (honored in 1968 for finding the key to cracking the genetic code), Dr. Julius Axelrod (honored in 1970 for discoveries concerning chemical transmitters in the nervous system ), and Dr. D. Carleton Gajdusek (honored in 1976 for identifying the cause of kuru, a fatal infectious disease that affects the nervous system). Today, intramural researchers continue to work on projects that will, ultimately, improve the health of the public.

Since its humble beginning as a one-room laboratory of hygiene, the NIH has become the largest biomedical research enterprise in the world. This well-funded public program has enabled scientists to make tremendous strides in preventing, controlling, detecting, and treating disease. Still, there are enduring questions for researchers at each of the twenty-seven institutes and centers to tackle, such as ways to prevent and treat cancer, heart disease, blindness, arthritis , diabetes, Alzheimer's disease, depression , drug misuse, and AIDS. To pursue these and other issues, every year the NIH posts hundreds of requests for proposals (RFPs), encouraging scientists to submit grant proposals on different topics. At the beginning of the twenty-first century, the NIH is especially interested in supporting research that will improve the health of infants and children, women, older adults, and minorities. Future projects will help scientists, practitioners, and educators better understand how biological processes, behaviors, and lifestyle practices impact health and disease. For example, more will certainly be learned about nutrition-related illnesses and how diet influences gene expression . By directing research in these areas, the NIH is leading the way to better health for everyone.

see also Goldberger, Joseph.

Jessica Schulman

Bibliography

Brown, Michael S., and Goldstein, Joseph L. (1984). "How LDL Receptors Influence Cholesterol and Atherosclerosis." Scientific American 251:52–60.

Pittenger, Mark F.; Mackay, Alastair, M.; Beck, Stephen C.; Jaiswal, Rama K.; Douglas, Robin; Mosca, Joseph D.; Moorman, Mark A.; Simonetti, Donald W.; Craig, Stewart; and Marshak, Daniel R. (1999). "Multilineage Potential of Adult Human Mesenchymal Stem Cells." Science 284:143–147.

Roe, Daphne A. (1973). A Plague of Corn: A Social History of Pellagra. New York: Cornell University Press.

Starr, Paul (1982). The Social Transformation of American Medicine. Washington, DC: Basic Books.

Internet Resources

National Institutes of Health (2001). "Press Release: FY 2002 President's Budget." Available from <http://www4.od.nih.gov/officeofbudget/press2002.pdf>

National Institutes of Health, Stetton Museum of Medical Research. "Historical Resources." Available from <http://history.nih.gov>

NATIONAL INSTITUTES OF HEALTH

NATIONAL INSTITUTES OF HEALTH (NIH), established at the Marine Hospital, Staten Island, N.Y., in 1887 as the Laboratory of Hygiene, for research on cholera and other infectious diseases. In 1891 it was renamed the Hygienic Laboratory and moved to Washington, D.C., and in 1930, as a result of the Ransdell Act, it became the National Institute of Health. In 1937 it incorporated the National Cancer Institute, and the following year Congress authorized the construction of new, larger laboratory facilities and the transfer of the National Institute of Health (NIH) to Bethesda, Md. Legislation in 1948 established a National Heart Institute and changed the name of the National Institute of Health to National Institutes of Health.

An agency of the Department of Health, Education and Welfare since that department's establishment in 1953, NIH has the mission of improving the health of all Americans. To achieve this goal it conducts biomedical research; provides grants to individuals, organizations, and institutions for research, training, and medical education; assists in the improvement and construction of library facilities and resources; and supports programs in biomedical communications. From its beginnings in a one-room laboratory, NIH has developed into a large research center. The NIH campus consists of over 300 acres and includes laboratories, libraries, and clinical facilities for highly sophisticated research into the biomedical sciences. NIH also has annual lectures, honors, exhibits, and symposia.

Its intramural program supports research in NIH laboratories on the Bethesda, Md., campus, and its extramural program distributes grants to university investigators across the United States and makes collaborative arrangements with researchers in other countries. The NIH annual budget in the early 1990s was more than $8 billion, and personnel on the Bethesda campus numbered more than 16,000. In 1993 Congress directed the NIH to include more women in research designs and analysis instead of continuing to concentrate on studies involving only men. By 1994 the NIH consisted of seventeen institutes (Aging; Alcohol Abuse and Alcoholism; Allergy and Infectious Diseases; Arthritis and Musculoskeletal and Skin Diseases; Cancer; Child Health and Human Development; Deafness and Other Communication Disorders; Dental Research; Diabetes and Digestive and Kidney Diseases; Drug Abuse; Environmental Health Sciences; Eye; General Medical Sciences; Heart, Lung, and Blood; Mental Health; Neurological Disorders and Stroke; and Nursing Research); two divisions (Computer Research and Technology and Research Grants); four centers (Center for Research Resources; John E. Fogarty International Center; National Center for Human Genome Research; and Warren Grant Magnuson Clinical Center); three offices (Women's Health; Alternative Medicine; and Minority Health); the National Library of Medicine; and the Children's Inn at NIH. The NIH also funds three field units (the Gerontology Research Center in Baltimore, Md.; the Rocky Mountain Laboratories in Hamilton, Mont.; and the NIH Animal Center in Poolesville, Md.). NIH has joined with other agencies to advance biomedical research. In one of the larger projects, NIH and the Howard Hughes Medical Institute launched a multimillion-dollar cooperative program to encourage physicians to enter research.

BIBLIOGRAPHY

Ahrens, Edward H., Jr. The Crisis in Clinical Research: Overcoming Institutional Obstacles. New York: Oxford University Press, 1992.

Kelley, William N., et al. Emerging Policies for Biomedical Research. Washington, D.C.: Association of Academic Health Centers, 1993.

National Institutes of Health (U.S.) Division of Public Information. NIH Almanac. Bethesda, Md.: U.S. Department of Health, Education and Welfare, Public Health Service, National Institutes of Health, 1975.

———. NIH Almanac. Bethesda, Md.: U.S. Department of Health, Education and Welfare, Public Health Service, National Institutes of Health, 1992.

Reagan, Michael D. The Accidental System: Health Care Policy in America. Boulder, Colo.: Westview Press, 1999.

ManfredWaserman/c. w.

See alsoClinical Research ; Health and Human Services, Department of ; Hygiene ; Laboratories ; Medical Research .