Most MBoC readers will be surprised to learn that the organization we today call the NIH can be traced back as far as 1879. At first a loosely defined series of federal bodies overseeing medical science and U.S. public health, usually more in terms of policy than funding, these evolved over the next 70 years into a more coherently organized set of intermeshed operating agencies. A comprehensive treatise on the history of NIH peer review by Richard Mandel (Mandel, 1996 ) vividly recounts that in the post–World War II era the NIH dramatically morphed from an internal policy group into an outward-reaching funding agency, a transformation that was effected primarily by the 1946 creation of the Division of Research Grants within NIH, catalyzed by the visionary Cassius Van Slyke. Notwithstanding the growing intramural research program of NIH itself, the mounting requests for extramural funding at this time required the creation of a defined review system. One of the most evocative points Mandel brings forth is how diligently and passionately NIH officials such as Van Slyke visited universities and medical schools throughout the United States to promote the emerging existence of accessible funds for deployment outside, not just within, the walls of the NIH. We frustrated applicants today can hardly imagine a time when NIH officials went out as “circuit riders” to announce the ready availability of funds, but it really happened.

In 1958, the NIH Study Section on Biophysics and Biophysical Chemistry did a rather remarkable thing. In addition to dutifully reviewing grant applications at their regular meetings, during the breaks, as well as in correspondence and phone calls between scheduled meetings, the members of this study section decided, without ever being asked, to convene a special meeting. To its credit, the NIH Division of Research Grants supported this idea, both conceptually and financially. The meeting, entitled The Study Program in Biophysical Science, was held in Boulder, Colorado, from 20 July to 16 August 1958—obviously not a standard study section meeting time, but one conducive to a retreat at a pleasant site and in keeping with the notion of “study.” In addition to the study section members, it involved a judicious mix of 120 senior and junior scientists. Afterward, several of the leaders of this monumental meeting decided, in consultation with the study section's members, that many of the talks could form the basis of a textbook. These leaders were John L. Oncley (Harvard Medical School), Francis O. Schmitt (MIT), Robley C. Williams (University of California, Berkeley), Murray D. Rosenberg (Rockefeller Institute), and Richard H. Bolt (MIT). Oncley and Schmitt were the senior statesmen, Williams was midcareer (50 years old at the time), and Rosenberg was a very young colleague of the developmental biologist and study section member Paul Weiss. Bolt was an acoustical engineer at MIT whom the persuasive Schmitt corralled into helping with the book, in part because Bolt was at the time serving a stint at the National Science Foundation (NSF) and was able to garner some support for the project. (Note that the NSF and the NIH collaborated in funding this project.) Over the next year, the book organizers invited, cornered, and coerced a cadre of speakers from the Boulder meeting to each write a chapter. The result was a textbook (Figure 2) that constituted a unique and definitive statement on the states of various subjects within the combined fields of cell physiology, neurobiology, and biophysics (Oncley et al., 1959 ). In biophysics and its outreaches, touching and indeed informing cell biology in the field's foundational years, nothing like Oncley et al. had ever come forth. As a graduate student in 1963, I encountered this book, with chapters written by luminous stars of cell biology such as the electron microscopists H. Stanley Bennett, Fritiof Sjo˝strand, H. Fernandez-Moran, and Alan Hodge, as well as by the pioneering practitioner of polarized light microscopy Shinya Inoué, the prescient developmental biologist Paul Weiss, and the visionary cytogeneticist Ted Puck. Within 3 years of the book's publication, three of the chapter authors had received a Nobel Prize—Arthur Kornberg in 1959, Melvin Calvin in 1961, and John Kendrew in 1962—and a few years later two others had as well—Halden K. Hartline in 1967 and Bernard Katz in 1970. There is no book on my shelf more worn from very frequent pulling out than this one, and it was all from the “other mission” of this NIH study section.

As an “interview” for the NIH Cell Biology Study Section in 1975, I went on a site visit at the University of Texas at Galveston for the review of a program-project grant application by Barbara Bowman and colleagues. She had come up with an ingenious assay of the viscosity of sputum from cystic fibrosis patients—a clinically critical parameter—based on the degree of inhibition of ciliary beating in the gills of oysters. I was fascinated by her insight and the superb quality of her science (her ingenious assay was essentially a kymographic report for the amount of polymerized actin in the sputum). At this site visit I met two future ASCB presidents who were collaborators on her project: T. C. Hsu and Bill Brinkley. Their key roles complemented Dr. Bowman's expertise perfectly—a triple-stranded helix. I can remember this site visit vividly, as if it happened last week. In any case, I apparently passed this trial run and was invited to join the Cell Biology Study Section in the fall of 1975. The chair at the time was the MIT embryologist Paul Gross, who was succeeded a year later by the Stanford biochemist David Korn and then, another year later, by the Purdue developmental biologist L. Dennis Smith.

This essay was not intended to pile on to the avalanche of criticism of the NIH extramural review process. Nor do I suspect that the second function of NIH study sections I have portrayed here can be reactivated any time soon. I would simply like us all to think about this and gather our thoughts. One specific question is the following: how much of the NIH extramural budget should be in the hands of well-meaning program directors and the grant applications they solicit, followed by arranged ad hoc study sections they empanel? I think this has gotten somewhat out of control, although some of these program director initiatives have certainly been effective. The issue here is one of appropriate balance.