Introduction

The NIH traces its roots to 1887, when a one-room laboratory was created within the Marine Hospital Service (MHS), predecessor agency to the U.S. Public Health Service (PHS). The MHS had been established in 1798 to provide for the medical care of merchant seamen. One clerk in the Treasury Department collected twenty cents per month from the wages of each seaman to cover costs at a series of contract hospitals. In the 1880s, the MHS had been charged by Congress with examining passengers on arriving ships for clinical signs of infectious diseases, especially for the dreaded diseases cholera and yellow fever, in order to prevent epidemics. During the 1870s and 1880s, moreover, scientists in Europe presented compelling evidence that microscopic organisms were the causes of several infectious diseases. In 1884, for example, Koch described a comma-shaped bacterium as the cause of cholera.

Officials of the MHS followed these developments with great interest. In 1887, they authorized Joseph J. Kinyoun, a young MHS physician trained in the new bacteriological methods, to set up a one-room laboratory in the Marine Hospital at Stapleton, Staten Island, New York. Kinyoun called this facility a "laboratory of hygiene" in imitation of German facilities and to indicate that the laboratory's purpose was to serve the public's health. Within a few months, Kinyoun had identified the cholera bacillus in suspicious cases and used his Zeiss microscope to demonstrate it to his colleagues as confirmation of their clinical diagnoses. "As the symptoms . . . were by no means well defined," he wrote, "the examinations were confirmatory evidence of the value of bacteria cultivation as a means of positive diagnosis."

The move to Washington

In 1891, the Hygienic Laboratory, as it came to be called, was moved to Washington, D.C., near the U.S. Capitol. For the next decade, Kinyoun remained the sole full-time staff member. He inaugurated a training program in bacteriology for MHS officers and conducted numerous tests of water purity and air pollution for the District of Columbia and the Congress. In 1901, the laboratory was belatedly recognized in law when Congress authorized $35,000 for construction of a new building in which the laboratory could investigate "infectious and contagious diseases and matters pertaining to the public health." Occupied in 1904, this building was located at 25th and E Streets, N. W., in Washington, D.C. The founding legislation for the NIH, therefore, resides in a routine supplemental appropriations act. Many other scientific agencies of the federal government were also created via "money bills." Congress was not convinced that such bureaucracies would prove demonstratively useful, so it chose to preserve the option of divesting the government of them simply by not renewing their funding.

In 1902 two acts contributed significantly to the emergence of the Hygienic Laboratory as a center for research within the federal government. The first reorganized the MHS and renamed it the Public Health and Marine Hospital Service (PH-MHS), moving it toward its status as the chief U.S. public health agency. More importantly for the Hygienic Laboratory, the act launched a formal program of research by designating the pathological and bacteriological work as the Division of Pathology and Bacteriology and by creating three new components that represented the most fruitful areas for research at that time: the Divisions of Chemistry, Pharmacology, and Zoology. The importance of these new programs was underscored by the provision that the PH-MHS could hire scientist researchers with Ph.D.'s to head them. Up until this time, the professional staff had been limited to physicians.

Biologics

The Biologics Control Act was a second piece of legislation enacted in 1902 that had major consequences for the Hygienic Laboratory. It charged the laboratory with regulating the production of vaccines and antitoxins, thus making it a regulatory agency four years before passage of the better-known 1906 Pure Food and Drugs Act. The danger posed by biological products-technologies that had emerged from bacteriologic discoveries—resulted from their production in animals and their administration by injection. Diphtheria antitoxin, for example, was made by inoculating horses with increasingly concentrated doses of diphtheria bacteria, then bleeding the animals to obtain their blood serum, which was bottled as antitoxin. When injected into the body of a patient suffering from diphtheria, the antibodies in the horse serum neutralized the toxin causing the patient’s symptoms. Possibilities for contamination lurked at every stage of the antitoxin production process, and the amount of horse serum necessary to cure was initially undefined. In 1901, thirteen children in St. Louis died after receiving diphtheria antitoxin contaminated with tetanus spores. This tragedy spurred Congress into passing the Biologics Control Act. Between 1903 and 1907 standards were established and licenses issued to pharmaceutical firms for making smallpox and rabies vaccines, diphtheria and tetanus antitoxins, various other antibacterial antisera, thyroidectomized goat serum, and horse serum. The research required to set standards led investigators into new fields, such as immunology, in order to understand the sudden deaths that sometimes followed repeated injections of biologics prepared in foreign-protein media such as horse serum. (Note: In 1972, responsibility for regulation of biologics was transferred to the Food and Drug Administration.)

In 1912 another Service reorganization act shortened the name of the PH-MHS to Public Health Service (PHS). This brief act also authorized the laboratory to conduct research into non contagious diseases and into the pollution of streams and lakes in the United States. Under this law, PHS officer Joseph Goldberger in 1914 conducted an epidemiological study that identified the cause of the disease pellagra, a scourge of poor Southerners, as a dietary deficiency and brewers’ yeast as a cheap and widely available cure. Also, Earl B. Phelps, then director of the Division of Chemistry, described the behavior of oxygen in water that fostered better understanding of the effects of pollution in lakes and rivers.

WWI and the Ransdell Act of 1930

During World War I, the Public Health Service attended primarily to sanitation of areas around military bases in the U.S. The staff of the Hygienic Laboratory traced the cause of anthrax outbreaks among the troops to contaminated shaving brushes and discovered that the bunion pads widely used to cover smallpox vaccinations could harbor tetanus spores. In 1916, the director of the laboratory, Dr. George McCoy , hired the laboratory's first female bacteriologist, Dr. Ida Bengtson. When the 1918 influenza pandemic struck Washington, physicians from the laboratory were pressed into service treating patients in the District of Columbia because so many local doctors fell ill.

In 1930, the Ransdell Act changed the name of the Hygienic Laboratory to National Institute (singular) of Health (NIH) and authorized the establishment of fellowships for research into basic biological and medical problems. The roots of this act extended to 1918, when chemists who had worked with the Chemical Warfare Service in World War I sought to establish an institute in the private sector to apply fundamental knowledge in chemistry to problems of medicine. In 1926, after no philanthropic patron could be found to endow such an institute, the proponents joined with Louisiana Senator Joseph E. Ransdell to seek federal sponsorship. The truncated form in which the bill was finally enacted in 1930 reflected the harsh economic realities imposed by the Great Depression. Nonetheless, this legislation marked a change in the attitude of the U.S. scientific community toward public funding of medical research.

NCI

Seven years later, the National Cancer Institute (NCI) was created with sponsorship from every Senator in Congress. This unusual agreement among lawmakers revealed growing concern in the nation about cancer and foreshadowed the categorical-disease structure of NIH that has characterized the agency since that time. The NCI was authorized to award grants to nonfederal scientists for research on cancer and to fund fellowships at NCI for young researchers. Under the original legislation, NCI's administrative relationship to NIH was not specified. A research facility was constructed, however, as "Building 6" of a new NIH campus in Bethesda, Maryland, that was occupied between 1938 and 1941. In the 1944 PHS legislation, NCI was specifically designated as a component of NIH.

During World War II, the NIH focused almost entirely on war-related problems. At the outset, a Division of Public Health Methods worked with the Selective Service to analyze why 43 percent of potential inductees were unfit for general military service and 28 percent were unfit for any military service. The most common cause of rejection, it was found, was defective teeth. Many of those rejected also had syphilis. The Division of Industrial Hygiene collaborated with the Divisions of Pathology and Pharmacology to conduct research on hazardous substances and conditions to protect workers in war industries. The investigators examined new explosives, developed methods to determine the amount of lead or TNT in urine so that workers could be tested for undue exposure, and demonstrated the affinity of lead for bone tissue. Other investigators determined that the vapors of methyl, ethyl, isopropyl, and butyl alcohol were acutely toxic to workers. This work improved conditions of employment for more than 300,000 workers in defense industries.

World War II Research and the Grants Program

Vaccines and therapies to deal with tropical diseases were also critically important to the war effort. At the NIH's Rocky Mountain Laboratory in Hamilton, Montana, yellow fever and typhus vaccines were prepared for military forces. In Bethesda as well as through grants to investigators at universities a synthetic substitute for quinine was sought to treat malaria. The Division of Biologics investigated the fever-producing properties of bacteria which might appear as contaminants of plasma, serum albumin, or whole blood, and developed sampling techniques to avoid contamination. Research in the Division of Chemotherapy revealed that sodium deficiency was the critical element leading to death after burns or traumatic shock. This led to the widespread use of oral saline therapy as a first-aid measure on the battlefield. NIH and military physiologists collaborated on research into problems related to high altitude flying. They determined the altitude at which oxygen had to be administered to prevent pilots from blacking out and designed an apparatus to supply extra oxygen efficiently. They also studied the relation of pressure changes to bubble formation in liquids to address the problem of emboli forming in the blood of pilots. Other tests were made to evaluate the efficiency of flight clothing, especially electrically heated suits, and to determine the effect of altitude on visual acuity and the use of visual devices for improvement of night vision.

As the war drew to a close, PHS officials guided through Congress the 1944 Public Health Service Act, which defined the shape of medical research in the post-war world. Two provisions in particular had an impact on the NIH. First, in 1946 the successful grants program of the NCI was expanded to the entire NIH. From just over $4 million in 1947, the program grew to more than $100 million in 1957 and to $1 billion in 1974. The entire NIH budget expanded from $8 million in 1947 to more than $1 billion in 1966. Between 1955 and 1968, NIH Director James A. Shannon presided over the spectacular growth that is now fondly remembered as "the golden years" of NIH expansion.

New Institutes

Accompanying growth in the grants program was the proliferation of new categorical institutes. Between 1946 and 1949, voluntary health organizations motivated Congress to create institutes for research on mental health, dental diseases, and heart disease. In 1948, language in the National Heart Act also made the name of the umbrella organization plural: National Institutes of Health. The original divisions of the old National Institute of Health were divided into two newly created institutes: the National Microbiological Institute (NMI) and the Experimental Biology and Medicine Institute (EMBI). The tradition of using such academic medical names, however, was being transformed by the conviction that institutes named after diseases stood a better chance for being funded by Congress. In 1950, the EMBI was absorbed by the newly created National Institute of Arthritis and Metabolic Diseases. In 1955 the NMI similarly became part of the National Institute of Allergy and Infectious Diseases. By 1960 there were ten components. This number increased by 1970 to 15, and by 1998 the NIH had 27 institutes and centers.

In addition, specialized offices such as the Office of AIDS Research, were created but subsumed administratively under existing components.

The Clinical Center

The second key provision of the 1944 Public Health Service Act authorized the National Institute of Health to conduct clinical research. After the war, Congress provided funding to build a research hospital, now called the Warren Grant Magnuson Clinical Center, on the NIH campus in Bethesda. Opened in 1953 with 540 beds, the hospital was designed to bring research laboratories into close proximity with hospital wards in order to promote productive collaboration between laboratory scientists and clinicians. Special care was taken to communicate to local physicians that the Clinical Center dealt only with research and did not represent a move toward "socialized medicine," which was opposed by most physicians in the 1950s. The Clinical Center was also launched under the shadow of revelations about Nazi medical experiments during World War II, thus a medical board was charged with reviewing research protocols to ensure that participants would not be harmed. During the 1960s institutions receiving NIH grant awards were required to state the ethical principles guiding their research involving humans. In 1979, the oversight process was codified into written guidelines for research on human subjects. The NIH Office for Protection from Research Risks, utilizing a computerized tracking system, now monitors over 500 major institutions and more than 5,000 smaller institutions, community hospitals, and clinics where research is conducted.

Any research protocol raises ethical uses about the treatment of research subjects, whether human or animal. Since its inception in 1887, the NIH has maintained the necessity for animal research and simultaneously has insisted upon humane treatment. "Animals are to be used in the proper work of the laboratory," wrote Hygienic laboratory director Dr. Milton J. Rosenau in 1904, but anything which inflicts pain upon them will not under any circumstances be allowed." In 1963 the NIH issued a guide for the care and use of laboratory animals that has gone through many editions and is considered a standard reference for scientific institutions. During the early 1970s, an official policy regarding the humane use of animals introduced the concept of institutional animal care committees for those institutions receiving NIH funds. In 1975 members of "study sections," the scientific peers of grant applicants who judge the scientific potential of each application, were assigned the responsibility of considering animal welfare in proposed projects before funds were awarded. Since 1985, NIH officials have conducted unannounced site visits to spot-check animal facilities and laboratory research programs.

Expansion

Toward the end of the 1960s, the growth of NIH budgets slowed considerably, in part because of inflation in the U.S. economy and the advent of new programs such as Medicare and Medicaid that competed for congressional "health" funding. Tighter budgets also led to debate over the relative efficacy of unfettered basic research versus goal-directed applied research. In the early 1970s Congress authorized major initiatives against two chronic killers, cancer and heart disease. The National Cancer Act of 1971 created fifteen new research, training, and demonstration cancer centers. The following year the National Heart, Blood Vessel, Lung, and Blood Act mandated an expanded program against all aspects of heart disease, including high blood pressure, elevated cholesterol levels, stroke, and particular blood diseases such as sickle-cell anemia. The AIDS crisis of the 1980s similarly provided at first an opportunity for goal-directed research quickly to uncover an effective therapy or vaccine. When no quick solution was forthcoming, leaders of the research effort against AIDS began to emphasize study of basic immunological processes as the most efficient strategy to find an effective therapy or preventative.

Thorny social and ethical issues were also raised in the 1970s by the first recombinant DNA experiments. Dr. DeWitt Stetten, Jr., then the NIH Deputy Director for Science, chaired a national committee of scientists to develop guidelines for the new technology. Intramural investigators associated with the National Institute of Allergy and Infectious Diseases conducted biosafety studies which helped to demonstrate that recombinant DNA research did not pose great risk of unleashing deadly novel organisms. Since that time, research on the molecular level has transformed the way scientists study most diseases. In the late 1980s, NIH and the Department of Energy launched the Human Genome Project with the goal of mapping and sequencing the entire collection of human genes. The medical, ethical, and legal implications of this work continue to have profound effects on society.

National Institute of Health Centers

Research in medicine knows no international boundaries. Since its founding, the NIH has maintained close relations with many of its Western Hemisphere counterparts through the Pan American Sanitary Bureau, now called the Pan American Health Organization . In 1947, the first NIH grants were awarded to investigators in foreign universities, and in 1968, the creation of the John E. Fogarty International Center institutionalized coordination of international exchanges at NIH. The Fogarty Center also maintains liaisons with the World Health Organization and European medical research organizations. One branch of the center supports translation, documentation, and critical reviews of new health science information.

Worldwide biomedical communications are also fostered by the NIH's National Library of Medicine (NLM) . As the world's largest medical library, the NLM boasts a collection of more than 5.1 million items. Founded in 1836 as the library of the surgeon general of the Army, the NLM became a component of NIH in 1968. The NLM has made freely available on the World Wide Web a database holding the most current medical literature. Also available are LocatorPlus, the online catalog of books and manuscripts in the library, AIDSLINE, a subset of MEDLINE devoted to AIDS research, and various databases useful for researchers, practicing physicians, and members of the public who use the resources available for research on medical topics.

Biomedical Research

The close relationship between basic and clinical research at the NIH reflects Louis Pasteur's observation that science is indivisible: "There is only science and the fruits of science." On the NIH campus, intramural clinical investigators interact with their basic science colleagues with the aim of developing improved intervention strategies for treating the knottiest disease problems. The NIH also holds Consensus Development Conferences of investigators and physicians from around the world at which panels of experts appraise new modes of therapy or evaluate existing therapies about which questions have been raised. The first, held in 1977, recommended mammography as a routine diagnostic tool for breast cancer in women over fifty. Since then more than 100 Consensus Development Conferences have rapidly channeled research findings on devices, drugs, and medical or surgical procedures to practicing physicians.

Biomedical research and development is a continuing process. New knowledge yields new drugs, devices, and procedures; the study of how the products act yields more knowledge; refinements in knowledge then enable the development of even better therapies. Whether an idea originates in a university laboratory or starts with basic product research carried out in the private sector, important findings percolate through the entire scientific community. Each new finding serves as a building block for establishing a deeper understanding of human health and disease. The 1986 Technology Transfer Act codified and fostered partnerships between NIH research and private-sector development of therapeutic products.

NIH Successes

It is impossible to list all of the discoveries made by NIH-supported investigators. More than eighty Nobel prizes have been awarded for NIH-supported research. Five of these prizes were awarded to investigators in the NIH intramural programs. The intramural discoveries have included deciphering the genetic code that governs all life processes, demonstrating how chemicals act to transmit electrical signals between nerve cells, and describing the relationship between the chemical composition of proteins and how they fold into biologically active conformations. In turn, these basic research discoveries have led to greater understanding of genetically based diseases, to better antidepressants, and to drugs specially designed to target proteins involved in particular disease processes. Long-term research has dispelled preconceptions that morbidity and dementia are a normal part of the aging process. Some cancers have been cured and deaths from heart attack and stroke have been significantly lowered. Research has also revealed that preventive strategies such as a balanced diet, an exercise program, and not smoking can reduce the need for therapeutic interventions and thus save money otherwise expended for health care.

In 1887, Dr. Joseph Kinyoun could hardly have imagined the size and scope of the NIH's present program. As a result of the numerous scientific opportunities and policy decisions that make up the historical fabric of the NIH, this premier medical research institution is poised to foster even more significant contributions to human health in the twenty-first century.

The National Institutes of Health (NIH) (/ɛnaɪˈeɪtʃ/; each letter separately) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1870s, and is now part of the United States Department of Health and Human Services. The majority of NIH facilities are located in Bethesda, Maryland. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program.

As of 2013, the Intramural Research Program (IRP) had 1,200 principal investigators and more than 4,000 postdoctoral fellows in basic, translational, and clinical research, being the largest biomedical research institution in the world,^[5] while, as of 2003, the extramural arm provided 28% of biomedical research funding spent annually in the U.S., or about US$26.4 billion.^[6]

The NIH comprises 27 separate institutes and centers of different biomedical disciplines and is responsible for many scientific accomplishments, including the discovery of fluoride to prevent tooth decay, the use of lithium to manage bipolar disorder, and the creation of vaccines against hepatitis, Haemophilus influenzae (HIB), and human papillomavirus (HPV).^[7]

In 2019, the NIH was ranked #2 in the world for biomedical sciences by the Nature Index, which measured the largest contributors to papers published in a subset of leading journals from 2015–2018.^[8][9]

History[edit]

Ida A. Bengtson, a bacteriologistwho in 1916 was the first woman hired to work in the Hygienic Laboratory.^[10]

Dedication of first six NIH buildings by President Franklin D. Roosevelt in 1940

NIH campus in Bethesda, Maryland, in 1945

NIH's roots extend back to the Marine Hospital Service in the late 1790s that provided medical relief to sick and disabled men in the U.S. Navy. By 1870, a network of marine hospitals had developed and was placed under the charge of a medical officer within the Bureau of the Treasury Department. In the late 1870s, Congress allocated funds to investigate the causes of epidemics like cholera and yellow fever, and it created the National Board of Health, making medical research an official government initiative.^[11]

In 1887, a laboratory for the study of bacteria, the Hygienic Laboratory, was established at the Marine Hospital in New York.^[12][13] In the early 1900s, Congress began appropriating funds for the Marine Hospital Service. By 1922, this organization changed its name to Public Health Services and established a Special Cancer Investigations laboratory at Harvard Medical School. This marked the beginning of a partnership with universities. In 1930, the Hygienic Laboratory was re-designated as the National Institute of Health by the Ransdell Act, and was given $750,000 to construct two NIH buildings. Over the next few decades, Congress would markedly increase funding of the NIH, and various institutes and centers within the NIH were created for specific research programs.^[14] In 1944, the Public Health Service Act was approved, and the National Cancer Institute became a division of NIH. In 1948, the name changed from National Institute of Health to National Institutes of Health.

In the 1960s, virologist and cancer researcher Chester M. Southam injected HeLa cancer cells into patients at the Jewish Chronic Disease Hospital.^[15]:130When three doctors resigned after refusing to inject patients without their consent, the experiment gained considerable media attention.^[15]:133 The NIH was a major source of funding for Southam's research and had required all research involving human subjects to obtain their consent prior to any experimentation.^[15]:135 Upon investigating all of their grantee institutions, the NIH discovered that the majority of them did not protect the rights of human subjects. From then on, the NIH has required all grantee institutions to approve any research proposals involving human experimentation with review boards.^[15]:135

In 1967, the Division of Regional Medical Programs was created to administer grants for research for heart disease, cancer, and strokes. That same year, the NIH director lobbied the White House for increased federal funding in order to increase research and the speed with which health benefits could be brought to the people. An advisory committee was formed to oversee further development of the NIH and its research programs. By 1971 cancer research was in full force and President Nixon signed the National Cancer Act, initiating a National Cancer Program, President's Cancer Panel, National Cancer Advisory Board, and 15 new research, training, and demonstration centers.^[16]

Funding for the NIH has often been a source of contention in Congress, serving as a proxy for the political currents of the time. In 1992, the NIH encompassed nearly 1 percent of the federal government's operating budget and controlled more than 50 percent of all funding for health research, and 85 percent of all funding for health studies in universities.^[17] While government funding for research in other disciplines has been increasing at a rate similar to inflation since the 1970s, research funding for the NIH nearly tripled through the 1990s and early 2000s, but has remained relatively stagnant since then.^[18]

By the 1990s, the NIH committee focus had shifted to DNA research, and launched the Human Genome Project.^[19]

Leadership[edit]

The NIH Office of the Director is the central office responsible for setting policy for NIH, and for planning, managing and coordinating the programs and activities of all NIH components. The NIH Director plays an active role in shaping the agency's activities and outlook. The Director is responsible for providing leadership to the Institutes and Centers by identifying needs and opportunities, especially in efforts involving multiple Institutes.^[20] Within this Office is the Division of Program Coordination, Planning and Strategic Initiatives with 12 divisions including:

• Office of AIDS Research
• Office of Research on Women's Health
• Office of Disease Prevention
• Sexual and Gender Minority Research Office
• Tribal Heath Research Office
• Office of Program Evaluation and Performance

Locations and campuses[edit]

Intramural research is primarily conducted at the main campus in Bethesda, Maryland and Rockville, Maryland, and the surrounding communities.

The Bayview Campus in Baltimore, Maryland houses the research programs of the National Institute on Aging, National Institute on Drug Abuse, and National Human Genome Research Institute with nearly 1,000 scientists and support staff.^[21] The Frederick National Laboratory in Frederick, MD and the nearby Riverside Research Park, houses many components of the National Cancer Institute, including the Center for Cancer Research, Office of Scientific Operations, Management Operations Support Branch, the division of Cancer Epidemiology and Genetics and the division of Cancer Treatment and Diagnosis.^[22]

The National Institute of Environmental Health Sciences is located in the Research Triangle region of North Carolina.

Other ICs have satellite locations in addition to operations at the main campus. The National Institute of Allergy and Infectious Diseases maintains its Rocky Mountain Labs in Hamilton, Montana,^[23]with an emphasis on BSL3 and BSL4 laboratory work. NIDKK operates the Phoenix Epidemiology and Clinical Research Branch in Phoenix, AZ.

Research[edit]

Clinical Center – Building 10

As of 2017, 153 scientists receiving financial support from the NIH have been awarded a Nobel Prize and 195 have been awarded a Lasker Award.^[24]

Intramural and extramural research[edit]

NIH devotes 10% of its funding to research within its own facilities (intramural research), and gives >80% of its funding in research grants to extramural (outside) researchers.^[2] Of this extramural funding, a certain percentage (2.8% in 2014) must be granted to small businesses under the SBIR/STTRprogram.^[25] As of 2011, the extramural funding consisted of about 50,000 grants to more than 325,000 researchers at more than 3000 institutions.^[26] By 2018, this rate of granting remained reasonably steady, at 47,000 grants to 2,700 organizations.^[2] In FY 2010, NIH spent US$10.7bn (not including temporary funding from the American Recovery and Reinvestment Act of 2009) on clinical research, US$7.4bn on genetics-related research, US$6.0bn on prevention research, US$5.8bn on cancer, and US$5.7bn on biotechnology.^[27]

Public Access Policy[edit]

Main article: NIH Public Access Policy

In 2008 a Congressional mandate called for investigators funded by the NIH to submit an electronic version of their final manuscripts to the National Library of Medicine's research repository, PubMed Central (PMC), no later than 12 months after the official date of publication.^[28] The NIH Public Access Policy was the first public access mandate for a U.S. public funding agency.^[29]

NIH Interagency Pain Research Coordinating Committee[edit]

On February 13, 2012, the National Institutes of Health (NIH) announced a new group of individuals assigned to research pain. This committee is composed of researchers from different organizations and will focus to "coordinate pain research activities across the federal government with the goals of stimulating pain research collaboration… and providing an important avenue for public involvement" ("Members of new," 2012). With a committee such as this research will not be conducted by each individual organization or person but instead a collaborating group which will increase the information available. With this hopefully more pain management will be available including techniques for arthritis sufferers.^[30]

Economic return[edit]

In 2000, the Joint Economic Committee of Congress reported NIH research, which was funded at $16 billion a year in 2000, that some econometric studies had given a rate of return of 25 to 40 percent per year by reducing the economic cost of illness in the US. It found that of the 21 drugs with the highest therapeutic impact on society introduced between 1965 and 1992, public funding was "instrumental" for 15.^[31] As of 2011 NIH-supported research helped to discover 153 new FDA-approved drugs, vaccines, and new indications for drugs in the 40 years prior.^[32] One study found NIH funding aided either directly or indirectly in developing the drugs or drug targets for all of the 210 FDA-approved drugs from 2010 to 2016.^[33] In 2015, Pierre Azoulay et al. estimated $10 million invested in research generated two to three new patents.^[34]

Notable discoveries and developments[edit]

Since its inception, the NIH intramural research program has been a source of many pivotal scientific and medical discoveries. Some of these include:

• 1908 – George W. McCoy's discovery that rodents were a reservoir of bubonic plague.
• 1911 – George W. McCoy, Charles W. Chapin, William B. Wherry, and B. H. Lamb described the previously-unknown tularemia.
• 1924 – Roscoe R. Spencer and Ralph R. Parker developed a vaccine against Rocky Mountain spotted fever.
• 1930 – Sanford M. Rosenthal developed a treatment for mercury poisoning used widely before the development of dimercaptoethanol.
• 1943 – Wilton R. Earle pioneered the cell culture process and published a paper describing the production of malignancy in vitro, Katherine K. Sanford developed the first clone from an isolated cancer cell, and Virginia J. Evans devised a medium that supported growth of cells in vitro.
• 1940s-50s – Bernard Horecker and colleagues described the pentose phosphate pathway.
• 1950s – Julius Axelrod discovered a new class of enzymes, cytochrome P450 monooxygenases, a fundamental of drug metabolism.
• 1950 – Earl Stadtman discovered phosphotransacetylose, elucidating the role of acetyl CoA in fatty acid metabolism.
• 1960s – Discovered the first human slow virus disease, kuru, which is a degenerative, fatal infection of the central nervous system. This discovery of a new mechanism for infectious diseases revolutionized thinking in microbiology and neurology.
• 1960s – Defined the mechanisms that regulate noradrenaline, one of the most important neurotransmitters in the brain.
• 1960s – Developed the first licensed rubella vaccine and the first test for rubella antibodies for large scale testing.
• 1960s – Developed an effective combination drug regimen for Hodgkin's lymphoma.
• 1960s – Discovery that tooth decay is caused by bacteria.
• 1970s – Developed the assay for human chorionic gonadotropin that evolved into the home pregnancy tests.
• 1970s – Described the hormonal cycle involved in menstruation.
• 1980s – Determined the complete structure of the IgE receptor that is involved in allergic reactions.
• 1990s – First trial of gene therapy in humans.

NIH Toolbox[edit]

In September 2006, the NIH Blueprint for Neuroscience Research started a contract for the NIH Toolbox for the Assessment of Neurological and Behavioral Function to develop a set of state-of-the-art measurement tools to enhance collection of data in large cohort studies. Scientists from more than 100 institutions nationwide contributed. In September 2012, the NIH Toolbox was rolled out to the research community. NIH Toolbox assessments are based, where possible, on Item Response Theory and adapted for testing by computer.^{[citation needed]}

Funding[edit]

Budget and politics[edit]

Historical NIH budget^[35]YearBudget (millions)

To allocate funds, the NIH must first obtain its budget from Congress. This process begins with institute and center (IC) leaders collaborating with scientists to determine the most important and promising research areas within their fields. IC leaders discuss research areas with NIH management who then develops a budget request for continuing projects, new research proposals, and new initiatives from the Director. NIH submits its budget request to the Department of Health and Human Services(HHS), and the HHS considers this request as a portion of its budget. Many adjustments and appeals occur between NIH and HHS before the agency submits NIH's budget request to the Office of Management and Budget (OMB). OMB determines what amounts and research areas are approved for incorporation into the President's final budget. The President then sends NIH's budget request to Congress in February for the next fiscal year's allocations.^[36] The House and Senate Appropriations Subcommittees deliberate and by fall, Congress usually appropriates funding. This process takes approximately 18 months before the NIH can allocate any actual funds.^[37]

When a government shutdown occurs, the NIH continues to treat people who are already enrolled in clinical trials, but does not start any new clinical trials and does not admit new patients who are not already enrolled in a clinical trial, except for the most critically ill, as determined by the NIH Director.^{[38][39][40][41]}

Historical funding[edit]

Over the last century, the responsibility to allocate funding has shifted from the OD and Advisory Committee to the individual ICs and Congress increasingly set apart funding for particular causes. In the 1970s, Congress began to earmark funds specifically for cancer research, and in the 1980s there was a significant amount allocated for AIDS/HIV research.^[42]

Funding for the NIH has often been a source of contention in Congress, serving as a proxy for the political currents of the time. During the 1980s, President Reagan repeatedly tried to cut funding for research, only to see Congress partly restore funding. The political contention over NIH funding slowed the nation's response to the AIDS epidemic; while AIDS was reported in newspaper articles from 1981, no funding was provided for research on the disease. In 1984 National Cancer Institute scientists found implications that "variants of a human cancer virus called HTLV-III are the primary cause of acquired immunodeficiency syndrome (AIDS)," a new epidemic that gripped the nation.^[43]

In 1992, the NIH encompassed nearly 1 percent of the federal government's operating budget and controlled more than 50 percent of all funding for health research and 85 percent of all funding for health studies in universities.^[17] From 1993 to 2001 the NIH budget doubled. Since then, funding essentially remained flat, and during the decade following the financial crisis, the NIH budget struggled to keep up with inflation.^[44]

In 1999 Congress increased the NIH's budget by $2.3 billion^[42] to $17.2 billion in 2000.^[45] In 2009 Congress again increased the NIH budget to $31 billion in 2010.^[45] In 2017 and 2018, Congress passed laws with bipartisan support that substantially increasing appropriations for NIH, which was 37.3 billion dollars annually in FY2018.^[46][47]

Extramural research[edit]

Main article: NIH grant

Researchers at universities or other institutions outside of NIH can apply for research project grants (RPGs) from the NIH. There are numerous funding mechanisms for different project types (e.g., basic research, clinical research etc.) and career stages (e.g., early career, postdoc fellowships etc.). The NIH regularly issues "requests for applications" (RFAs), e.g., on specific programmatic priorities or timely medical problems (such as Zika virus research in early 2016). In addition, researchers can apply for "investigator-initiated grants" whose subject is determined by the scientist.

The total number of applicants has increased substantially, from about 60,000 investigators who had applied during the period from 1999 to 2003 to slightly less than 90,000 in who had applied during the period from 2011 to 2015.^[48] Due to this, the "cumulative investigator rate," that is, the likelihood that unique investigators are funded over a 5-year window, has declined from 43% to 31%.^[48]

R01 grants are the most common funding mechanism and include investigator-initiated projects. The roughly 27,000 to 29,000 R01 applications had a funding success of 17-19% during 2012 though 2014. Similarly, the 13,000 to 14,000 R21 applications had a funding success of 13-14% during the same period.^[49] In FY 2016, the total number of grant applications received by the NIH was 54,220, with approximately 19% being awarded funding.^[50] Institutes have varying funding rates. The National Cancer Institute awarded funding to 12% of applicants, while the National Institute for General Medical Science awarded funding to 30% of applicants.^[50]

Funding criteria[edit]

NIH employs five broad decision criteria in its funding policy. First, ensure the highest quality of scientific research by employing an arduous peer review process. Second, seize opportunities that have the greatest potential to yield new knowledge and that will lead to better prevention and treatment of disease. Third, maintain a diverse research portfolio in order to capitalize on major discoveries in a variety of fields such as cell biology, genetics, physics, engineering, and computer science. Fourth, address public health needs according to the disease burden (e.g., prevalence and mortality). And fifth, construct and support the scientific infrastructure (e.g., well-equipped laboratories and safe research facilities) necessary to conduct research.^[51]

Advisory committee members advise the Institute on policy and procedures affecting the external research programs and provide a second level of review for all grant and cooperative agreement applications considered by the Institute for funding.^[52]

Gender and sex bias[edit]

In 2014, it was announced that the NIH is directing scientists to perform their experiments with both female and male animals, or cells derived from females as well as males if they are studying cell cultures, and that the NIH would take the balance of each study design into consideration when awarding grants.^[53] The announcement also stated that this rule would probably not apply when studying sex-specific diseases (for example, ovarian or testicular cancer).^[53]

Stakeholders[edit]

General public[edit]

One of the goals of the NIH is to "expand the base in medical and associated sciences in order to ensure a continued high return on the public investment in research."^[54] Taxpayer dollars funding NIH are from the taxpayers, making them the primary beneficiaries of advances in research. Thus, the general public is a key stakeholder in the decisions resulting from the NIH funding policy.^[55]However, some in the general public do not feel their interests are being represented, and individuals have formed patient advocacy groups to represent their own interests.^[56]

Extramural researchers and scientists[edit]

Important stakeholders of the NIH funding policy include researchers and scientists. Extramural researchers differ from intramural researchers in that they are not employed by the NIH but may apply for funding. Throughout the history of the NIH, the amount of funding received has increased, but the proportion to each IC remains relatively constant. The individual ICs then decide who will receive the grant money and how much will be allotted.

Policy changes on who receives funding significantly affects researchers. For example, the NIH has recently attempted to approve more first-time NIH R01 applicants, or the research grant applications of young scientists. To encourage the participation of young scientists, the application process has been shortened and made easier.^[57] In addition, first-time applicants are being offered more funding for their research grants than those who have received grants in the past.^[58]

Commercial partnerships[edit]

In 2011 and 2012, the Department of Health and Human Services Office of Inspector General published a series of audit reports revealing that throughout the fiscal years 2000–2010, institutes under the aegis of the NIH did not comply with the time and amount requirements specified in appropriations statutes, in awarding federal contracts to commercial partners, committing the federal government to tens of millions of dollars of expenditure ahead of appropriation of funds from Congress.^[59]