Just 22 years after the Declaration of Independence, President John Adams signed a law that created the Marine Hospital Service, a medical center for merchant seamen. It later evolved into the Public Health Service and, in turn, the National Institute of Health or NIH. (The Institute would become plural later.)

During both world wars, a few select institutions in New England and California conducted biomedical research, tending to focus primarily on cancer and areas of interest to the armed forces. To broaden and publicize their goals, NIH officials often paid visits to universities and schools across the United States, recruiting faculty members to submit research proposals.

One such faculty member, Maxwell Wintrobe, was chair of the department of medicine at the University of Utah. He was encouraged to apply to the NIH for research funds and appears to have timed it just right. Because the NIH had not yet implemented a formal peer review or grant administration system, NIH director Rolla Dyer personally recommended to the Congress and public health officials Wintrobe's proposal to study muscular dystrophy.

Wintrobe's institutional grant application was duly approved. In 1945, he became the first scientist at a medical school to be awarded an extramural grant from the National Institute of Health. This $100,000 award was renewed annually for 33 years, launching NIH's extramural program and bringing a total of nearly $10 million to Utah's medical school.

Grant Politics

Wintrobe's long success with the NIH, however, was not entirely his own doing. According to Richard Mandel, NIH historian and author of the book, A Half-Century of Peer Review, the Public Health Service had been planning to "colonize areas of the country, which had not participated in the wartime research boom." For that reason, the federal government paid particular attention to "land-grant universities which had received short shrift in terms of [research] contracts," he explains.

Democrat Elbert Thomas, a political science professor at the University of Utah, was elected to the U.S. Senate in 1932. There, he sat on the Committee on Labor and Public Welfare, which oversaw the Public Health Service and the NIH. Thomas Parran, the U.S. Surgeon General, subsequently chose the senator's home state to receive federal research attention.

The First Grants Research Office

Although Congress had passed, in 1943 and 1944, two Public Health Service Acts to reorganize the health care system and authorize the award of extramural research grants, it wasn't until 1946, the year following Wintrobe's proposal, that the NIH officially opened its Office of Research Grants.

Under the direction of Cassius Van Slyke, who had been an assistant chief in the Public Health Service, NIH's grant-application and peer-review procedures were designed. But, despite the availability of federal awards, both Public Health Service and NIH officials, including the institute director, still had to travel across the country to solicit research applications.

Then Andrew Moyer, a scientist working at the Northern Regional Research Laboratory in Peoria, Illinois, developed a way to mass-produce penicillin, a technological development that dramatically changed the landscape of federal research funding.

Because large-scale fermentation processes made manufacturing the drug easy, the costs associated with penicillin research were considerably reduced. By early 1944, for example, production of the drug increased by almost 80-fold and the price of 100,000 units had dropped from $20 in 1943 to less than 10 cents by 1949. Consequently, thousands of dollars were suddenly freed up at the Office of Research Grants, and Van Slyke informed all U.S. medical schools that "if you have investigators who need these funds, let us hear by return mail."

The grants research staff, consisting of only a handful of people, was swamped with hundreds of letters and proposals. So, the staff wrote to scientists listed in the prestigious Men of Science directory and asked them to comment on the merit of the proposals. The National Advisory Health Council, which held grant-awarding authority over the NIH, used these expert opinions to identify creditable proposals. However, the overwhelming response from investigators seeking federal aid clearly showed that this ad hoc process of evaluation was not going to work.

By the end of 1946, 21 study sections had been created by the NIH, more than 200 scientists were signed up as reviewers, and the research office was renamed the Division of Research Grants. All NIH grant applications were now subject to a dual review system, which introduced a "technical review by a study section, to establish scientific merit, and summary review by an [institutional] Advisory Council, to establish priority of payment," explains Mandel. The standard application booklet was simple, consisting of a 4-page format with a 200-word limit. By comparison, today's submission materials resemble a slim thesis!

The separation of scientific and fiscal merit at the NIH made the review process more objective, because reviewers were independent of the institute and their "evaluations were made independently of the program needs of the intramural scientists," Mandel says. This grant-review process has remained essentially unchanged for 50 years.

War Babies

The end of WWII marked a relative return to normalcy in the United States. The scientific research community flourished, encouraging Congress to create additional establishments within the National Institute of Health. The National Heart Institute and the National Institute of Dental Research became part of the federal research initiative, causing this subdivision of the Public Health Service to be renamed the National Institute s of Health in 1948.

Some 2 years later, Congress and the Truman Administration finally approved a bill to establish the National Science Foundation (NSF). Unlike the NIH, which was primarily concerned with funding medical and health-related research, Congress decided that the NSF would support a wider range of scientific research, including geosciences, mathematics, and basic biology. The budget for the new foundation, less than $4 million at the time, became available 2 years later, in 1952.

The NSF's most recent budget request was for approximately $4 billion dollars. Although this is approximately three times less than NIH's current budget, it represents a near 1000-fold increase over the agency's first financial appropriations. Today, NSF's economic status allows the agency to support 20,000 scientists and research projects annually. (Unlike NIH, the foundation conducts no research of its own.)

Review Revolution

Applying for a grant from either the NIH or the NSF has become a very complicated and intense process for both applicant and reviewer. Today, first-time applicants compete alongside thousands of other new and established scientists, an experience that can be intimidating and frustrating. The NIH typically receives between 35,000 and 40,000 proposals a year, while the NSF gets roughly half that number. Only a quarter to a third of these proposals are ever funded.

The process of applying for a grant, as well as choosing from among the different types of grants, has become more complex. The bulk of the applications submitted to NIH are for research grants such as the well-known "R01" awards, which require time-consuming, detailed budget requests. This level of detail has commonly been considered a burden for applicants who prepare proposals and for reviewers who check and determine feasibility. The NIH plans to introduce new financial disclosure requirements in its grant-review system this year.

These new modular grant awards will require applicants to include budget justification in basic, $25,000 "chunks," " eliminating the need to supply itemized expense lists of equipment, supplies, and personnel in grant submissions. The new system will also allow reviewers to focus more on the science presented and less on the details of financial requests.

There are also plans to create an electronic network that will link different federal agencies, including the NIH and the NSF. The creation of "Fastlane," NSF's online grants administration procedure, and the future introduction of NIH's electronic processing system, the "NIH Commons," illustrates the evolution of federal biomedical and basic research support. But regardless of the technology involved, many young scientists view the whole funding application process as an abyss from which relatively few successful applicants emerge.

Next week, we continue to examine the review process of the NIH and NSF. We'll tell you what happens on grant delivery day, whom you should call to answer your questions, and how the final decisions are made to award a grant. It's time to review the reviewers!