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.