National Institutes of Health

Origins

In 1887, a laboratory for the study of bacteria, the Hygienic Laboratory, was established within the Marine Hospital Service, which at the time was expanding its functions beyond the system of Marine Hospitals into quarantine and research programs. It was initially located at the New York Marine Hospital on Staten Island.^[7][8][9] In 1891, it moved to the top floor of the Butler Building in Washington, D.C. In 1904, it moved again to a new campus at the Old Naval Observatory, which grew to include five major buildings.^[10]

In 1901, the Division of Scientific Research was formed, which included the Hygienic Laboratory as well as other research offices of the Marine Hospital Service.^[11] In 1912, the Marine Hospital Service became the Public Health Service (PHS).^[9] In 1922, PHS established a Special Cancer Investigations laboratory at Harvard Medical School. This marked the beginning of a partnership with universities.^[9]

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 at the Old Naval Observatory campus.^[9] In 1937, NIH absorbed the rest of the Division of Scientific Research, of which it was formerly part.^[11][12]

In 1938, NIH moved to its current campus in Bethesda, Maryland.^[9] 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.^[9] 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.

Later history

In the 1960s, virologist and cancer researcher Chester M. Southam injected HeLa cancer cells into patients at the Jewish Chronic Disease Hospital.^[13]: 130 When three doctors resigned after refusing to inject patients without their consent, the experiment gained considerable media attention.^[13]: 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.^[13]: 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.^[13]: 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 the 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.^[14]

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.^[15] 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.^[16]

By the 1990s, the NIH committee focus had shifted to DNA research and launched the Human Genome Project.^[17]

Intramural and extramural research

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.^[27] Of this extramural funding, a certain percentage (2.8% in 2014) must be granted to small businesses under the SBIR/STTR program.^[28] As of 2011^[update], the extramural funding consisted of about 50,000 grants to more than 325,000 researchers at more than 3000 institutions.^[29] By 2018^[update], this rate of granting remained reasonably steady, at 47,000 grants to 2,700 organizations.^[27] In FY 2010^[update], 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.^[30]

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.^[31] The NIH Public Access Policy was the first public access mandate for a U.S. public funding agency.^[32]

Economic return

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.^[33] 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.^[34] 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.^[35] In 2015, Pierre Azoulay et al. estimated $10 million invested in research generated two to three new patents.^[36]

Notable discoveries and developments

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–1950s: 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: Hari Reddi's identification and purification of bone morphogenetic proteins^[37]
• 1990s: First trial of gene therapy in humans.

Budget and politics

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.^[51] 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.^[52]

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.^{[53][54][55][56]}

Extramural research

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.^[63] 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%.^[63]

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.^[64] In FY 2016, the total number of grant applications received by the NIH was 54,220, with approximately 19% being awarded funding.^[65] 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.^[65]

Funding criteria

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.^[66]

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.^[67]

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