DRAFT 10/30/87 ) THE STORY OF THE NIH GRANTS PROGRAMS By Stephen P. Strickland, Ph.D. Carried out under NIH Grant No. 1-RO1-LMO4552-Ol _INTRO DU CTI ON Over the past twenty years, I have spent several lengthy segments of time examining the National Institutes of Health, its programs and its accomplishments. I have done so as a working political scientist, an officer of an association of higher education, and an independent analyst and writer. In my first book on NIH, Politics, Science and Dread Disease, published in 1972, I picked up the story of Pmerica's pursuit of better health through science where the late, great scholar, Richard H. Shyrock had left off in his American Medical Research, in 1947. I recorded the general growth and developnent of NIH 1n the larger context of the socio-political world in which it operates. In 1978, my second book on NIH, Research and the Health of Americans, emphasized my own views of how some organ1zat1onal and programnatic changes in the governnent's larger health policy framework could enable the Institutes to be even more effective. Not until 1986, with a grant from the National Institutes of Health (my first) 'iBS I able to spend focused time reviewing closely the role of the principal component of the agency for the support of biomedical research and training - the Grants Programs. I had come to know, and admire, some of those persons who helped to create the "new" program just after the Second World War. And I 'iBS already certain that the grants programs had been the principal reason for the United States having the largest, most diverse, most productive biomedical scientific enterprise any nation could boast. But until I began this project, I had not been able to explore and record this remarkable story in an ordered way. The project has been timely in several respects. First of all, 1987 was the one hundredth anniversary of the founding of the Hygienic' ) Laboratory of the U.S. Public Health Service, that small entity to which the NIH traces its origins. 1986 was the 150th year of the National Library of Medicine, the indispenable sister institution of NIH. 1986 also marked the fortieth anniversary of the creation of the Office of Research Grants, a deed which, I would argue, was as much a determinant of what the National Institutes of Health has become as any other single legislative or­ administrative action in the past century. To be able to understand the full story and to record its highlights, it was essential that I talk with those persons still with us who had been present at the creation of postwar program, or who came soon enough thereafter to have had a hand in shaping its direction. These included Dr. Ernest Allen, who helped Dr. Cassius J. Van Slyke set up the office in 1946, and Drs. David Price and Kenneth Endicott who joined soon afterwards. The pioneers also included Dr. J. Roderick Heller, the first Director of the National Heart Institute upon its creation in 1948; Dr;. Ralph Meader who joined NIH on the same day as Rod Heller, as its Associate Director for Extramural Programs and then ~nt to the National Cancer i Institute; Dr. J. Franklin Yeager, an early member of the team at the Heart Institute, some of whose "proteges" help run NIH today; Dr. Ralph Knutti, ) who came to NIH to help create the new Arthritis and Metabolic Diseases Institute in 1951, as Chief of Extramural Programs, and later served as Director of the National Heart Institute; and Dr. Frederick Stone, recruited by Dr. Van Slyke himself, who apprenticed with Ernest Allen in the Office of Research Grants and later became Director of the National Institute of General Medical Sciences. Their recollections and judgments -- including those about ideas, struggles, frustrations, successes and pleasures - are what give fuller flavor and more vital truth to what might otherwise be a bureaucratic history documented in the perhaps firmer but definitely colder, less'informing evidence of surrmary facts and figures. These pioneers are now in the autumn of their lives, but every one of than provided lively, thoughtful and solid accounts of the early period of the grants program and their experiences in it. One of the best oral histories I conducted was with my long-time acquaintance, Kenneth Endicott, whom I much admired. The interviews with him, in the spring of 1986, turned out to be the last in which he recorded his own personal history and perspective on the growth of the American medical research anpire. He died in the late sunmer of 1987. Thus this monograph is based significantly on the oral histories I undertook, eighteen of which have been presented to the National Library of Medicine and are available in its History of Medicine Division for use by other scholars, analysts, journalists, and any interested person. The interviews include those with figures of more recent times, such as Dr. James Wyngaarden, current Director of NIH; his predecessor, Dr. Donald Fredrickson, and Dr. John F. Sherman, another old and valued friend, who served as Deputy Director and Acting Director of the Institutes for a number of years, and has added to his insider's perspective a new one from his position as Executive Vice President of the Association of American Medical Colleges. I also had valuable sessions with the current directors of two Institutes, Dr. Ruth Kirschstein of the National Institute of General Medical Sciences, and Dr. Murray Goldstein of the National Institute of Neurological Diseases, Conmunicative Disorders and Stroke, and with Dr. Jerome Green, a thirty-year veteran of NIH who recently has become head of the Office of Research Grants. It is gratifying that others had an opportunity to interview, before their passing, Dr. Rolla E. Dyer, Director of NIH from 1942 to 1950, who was principally responsible for NIH's assuming responsibility for wartime research contracts that were still underway when the Office of Scientific Research and D:velop:nent went out of business at the end of 1945; arid with Dr. Cassius J. van Slyke, whom Dr. Dyer brought in as, ostensibly, a part-time supervisor of these contracts. Such interviews were done in the 1960s under the aegis of the Columbia University Oral History Project; oral histories with these important men were conducted by Harlan Phillips and are on file in the History of Medicine Division of the National Library of Medicine. ii Even when one has worked as often and as long as I have in an area such as this, it is impossible to collect, by oneself, all needed informa­ tion or to reconstruct particular passages of events. I am indebted to a number of persons for their help in this regard, including Dr. John Parascandola, Chief of the History of Medicine Division of the National Library of Medicine and his associate, Peter Hirtle; Dr. Jeanne Brand who, as an officer of the NLM and project officer for my grant, and a distin­ guished medical historian, gave useful and timely counsel at several important points; Dr. Jerome Green and his staff for helping update information on numbers and processes so that the work would be as current as possible; and to Dr. John Sherman of t h e ~ who once more, as in a number of earlier instances, helped to explain some historical and program­ matic contexts that I was unable easily to discern on my own. Particular thanks go to my three research assistants, Tamara G. Strickland, Hans R. Bachmann, and Michelle Sotiropoulos. My wife Tamara also served as my good and reliable "blue pencil" editor for the manuscript, as she always does. My assistant, Ms. Sotiro:r;x,ulos, not only helped on research and did all the typing -- beautifully - but also served as liaison with the whole spectrum of distinguished interviewees and other principals essential to the completion of the work. I want to record a special word of appreciation and admiration to my great friend, Frances Humphrey Howard of the National Library of Medicine. Her keen sense of the comparable importance of the past, the present, and the future - and of the ideas and individuals that link them -- inspired and nourished this undertaking. The monograph that follows is, obviously, a history of a program and, because that program has now become a large one and has always been housed in government, a bureaucracy. It is about science and health, free inquiry and accountability, basic science and disease. It is also a human story of what a few men with ideas and energy, a cause and a support system, can do for the good of all. Each of us can identify developnents or accomplish­ ments which seem to epitomize "ideas whose time has come." But examination of concrete cases shows that it is the specific application of human minds, hands and hearts to needs and possibilities that truly makes great things happen. This is certainly the case of the Grants Programs of NIH, as I hope the following pages make clear. STEPHEN P. STRICKLAND, PH.D. NOVEMBER 1987 0 iii THE STORY OF THE NIH GRANTS PROGRAMS Stephen P. Strickland, Ph.D. In the years of the Great ~pression, most everyone knew about the Public Health Service. They were the people who worked on pellagra, malaria and yellow fever, tuberculosis and venereal disease. They worked on these problems in Pllblic Health Service hospitals, many in seaport towns, and sometimes through physicians and sanitary engineers and public health workers employed by the states but supported with federal money. ) The Public Health Service was certainly working on the right problems in those times. Pellagra has been corrmon in rural areas of the South through the 1920s; PHS efforts had brought it under control by the 1930s. Dr. Thomas Parran, Surgeon Gmeral of the Puhl ic Health Service, reported that ''malaria was present in the United States in epidemic proportions during the surmners of 1934 and 1935 to a greater extent than any other ) period during the last twenty years. 11 1 An extraordinary number of persons were infected with venereal diseases. For most of the decade, more than a half-million new cases of syphilis and gonorrhea were recorded each year. Dr. Parran asserted: "Syphilis ranks with cancer, heart disease and pneumonia as leading causes of death." But yellow fever and malaria still loomed as major public health threats. 2 Section I, page 2 0 Dr. Kenneth Endicott, reflecting on his thirty-five years in the Public Health Service, recalled vividly the situation existing in the country when he was a medical student in the 1930s: A huge percentage of the population had syphilis; the general population, not just the Merchant Marines. The treatment for gonorrhea was improved very rapidly in the mid~'30s with the discovery of sulphanilamide. But syphilis could only be treated with heavy metals until after World War II when penicillin came in. Heavy metals included arsenic and bismuth and mercury. It required weekly treatments for several years. They alternated courses: intravenous ar,senic for about six week then intramuscular bismuth. · When I was a student in Colorado, the V.D. outpatient clinic had operated four days of the week. One day was ladies' arms, then ladies' hips, then men's arms, and men's hips. And you'd spend the whole morning giving intravenous arsenic or shooting bismuth into people's buttocks, hundreds and hundreds and hundreds of patients. At the time I was an intern, out of ten floors in the PUblic Health Service Hospital, two were devoted to veneral disease. 3 What the PUblic Health Service was especially known for in its efforts to combat these afflictions was its outreach to affected, usually poor, populations, bringing standard treatments of the day to those in need. Indeed, everywhere in the country there were public health programs in part supported by the national PUblic Health Service. Meanwhile, virtually nobody knew about the research going on in laboratories operated by the PUblic Health Service or about the few grants PHS made to scientists working in laboratories outside government. In 1938, the budget of the Public Health Service was over $20 million. $6 million was budgeted for its hospitals around the country and $8 million was for grants to states for a variety of public health programs. The National Cancer Institute received $400,000 that year, and the National Institutes of Health, $64,000. Of that combined amount, $140,000 was for Section I, page 3 extramural research grants, fellowships and training, and other programs directly related to the investigation of disease and the scientific components of it .4 A handful of scientists worked in the laboratory of the National Institute of Health in Washington, continuing a fifty-year old tradition. A few others in other sites under PHS supervision, including the one in Montana monitoring and investigating Rocky Mountain Spotted Fever. ) The 1930s were a time of legislative expansion of the research pro- gram. In 1930 the Ransdell Act changed the Hygienic Laboratory to the "National Institute of Health", placed new anphasis on research grants, and ) established a systan of fellowships. In that same year, another law gave the Surgeon <£neral authority to investigate the causes, treabnent and prevention of mental diseases. In 1935 land was acquired in Bethesda to ) build a permanent home for NIH, and in 1937 the National Cancer Act was adopted, making provision for grants and fellowships for cancer research as well as new laboratories for professionals in the Public Health Service's employ to investigate that dread disease. At the end of the decade, in 1939, the Public Health Service was transferred from the Treasury Depart­ ment to the Federal Security Agency, the predecessor of the ~partment of Health, Education and Welfare.5 Then came war. With the U.S. entry into World War II at the end of 1941 and the national mobilization that folloW:d, the Public Health Ser­ vice grew again, in traditional directions. The whole nation organized itself; young men - even up to middle age - volunteered in their country's cause. The possibility of serving in uniform in the U.S. Public Health Service instead of in the Army or Navy was appealing to some Section I, page 4 physicians and other health professionals who wanted to serve but not necessarily to fight. The military itself provided such an option. Dr. Martin CUrrmings was in the Army almost from the outbreak of the war, but as a young officer was going to medical school, first at the University of North Carolina then at Yale. He recalls two officers of the Public Health Service visiting the Yale Medical School: They came and talked to our class and said, "Hey, we're in the war too and we're short of officers. We have a series of hospitals around the country and we need medical officers." I decided that sounded pretty interesting. They had a hospital in Seattle and one in Staten Island, and one in Boston, so I agreed to have an interview with them. They said if I would join the PUblic Health Service I would be transfered from the Army and I would be assigned to a Marine Hospital. That's how I wound up in the PUblic Health Service. I went to the Boston Marine Hospital and I was in the ms from 1944 to 1953. 6 Others found themselves in the reverse situation. Ken Endicott bad joined the PUblic Health Service.in 1939, imnediately upon graduation from medical school at the University of Colorado, doing so because one of his professors had in fact been an officer of the ms and had told him about J the enterprise, and more importantly, because he was offered "a handsome stipend of $1,044 per year." When the war broke out, he was a quarantine officer in the Port of San Francisco and was delighted when he received orders to join the Coast Guard: But before I could carry out the orders, they were cancelled and they sent me to the penitentiary to do a research project on hanosexuals. In Springfield, Missouri, at the medical center for federal prisoners, they had collected 100 passive homo~exuals from the military and federal prisons and had them waiting for me there to set up a study to find out if there was something wrong with their sex hormones. So I really started winning the war right after Pearl Harbor, with this research project at a federal penitentiary. 7 Section I, page 5 Another assignment was in the wings for Dr. Endicott. Within six months he was transfered to the National Institute of Health to do pathology in connection with research on nutrition and blood formation. These illustrations suggest the fluid and cooperative manner in which all agencies of the government, civilian and military, and indeed all professions, joined in the war effort. Army officers became Public Health Service officers; PHS officers became Coast Guard officers; medical students switched schools to make room for visiting allied officers whose facilities in Europe, particularly in England, had been bombed. Federally supported research was carried out in ms laboratories by persons from other divisions of government; a quarantine officer one day became a laboratory researcher the next. The PI-IS Commissioned Officer Corps had been statutorily authorized in 1889 as a mobile corps subject to duty anywhere upon assignment. But the wartime situation produced new possibilities for such assignments never before dreamed of. One example was that of Dr. Boyd R. Sayers, who, without giving up his PHS commission, was named by President Roosevelt as Director of the Bureau of the Mines. The pattern of cooperation was so extensive and so varied that it had the air of confusion. And the confusion - of function, of assignment, of who was paying who's salary to do what - masked both considerable general growth in the PUblic Health Service and considerable stability in its internal research program. As regards the enormous, almost universal desire of adult Americans to volunteer for the war effort, Dr. J. Roderick Heller recalls: We would take any sort of person into the PUblic Health Service if he was wann! It was about like that, but not quite that primitive. Dentists, medical officers, engineers, nurses, technicians, sanitarians, and public health personnel ~ect1on 1, page b 0 were either brought in as civil servants or as comnissioned officers, depending on their wishes and whether they would qualify. 8. In 1940 there were probably no more than one thousand comnissioned officers in the Public Health Service, a number which increased rapidly for the next several years and reached its zenith by the war's end. But because Public Health Service Officers were detailed to assigrnnents of such myriad variety and under the most assorted auspices, the growth pattern was not as striking at the time as it seemed in retrospect. Furthermore, millions of Americans were donning uniforms, and those who were declared ineligible to serve in the military - or the Public Health Service or the Coast Guard -- put on the caps and stripes of the Civil Air Patrol or the Red Cross. All considered themselves to be wearing the uniform of their country in time of desperate need and urgent business and few thought much about specific institutions or branches or corps beyond the war's end. All the while, the laborato~y of the National Institute of Health continued perking along out in Bethesda, altering its work only slightly from earlier objectives or priorities. Dr. Endicott recalled: ) The people interested in infectious diseases devoted a lot of attention to the develop:nent of vaccines for tropical diseases or diseases likely to be encountered in combat zones. There was a very active program, for example, in malaria control, and devel­ op:nent of substitutes for quinine because the source of quinine was largely cut off by [enemy] submarine activities. So that those who had been involved in the Laboratory of Industrial Hygiene became involved ••• in various toxicological studies related to the war effort. There was a project on toxicology of DDT; and I remanber working on projects on the toxic effects of sane of the cutting oils that they were using in war production facilities .9 One surprising thing was that many of the basic research people at NIH during the war just kept on doing basic research. The scientific staff Section I, page 7 were predominantly corrmissioned officers, and they were part of the armed forces, so they stayed where they were. The exception was an interesting one: People, particularly those in the Cancer Institute interested in radiation, radiation biology, radiation injury, and so on, vanished. They were taken to a very secret place in oakridge, Tennessee and they sort of disapPjared from the scene. There they manned the biology division. 0 II The coordination of the nation's scientific supplement to the war effort was concentrated in a few hands, led by a few experienced individuals. Dr. vannevar Bush, Science Advisor to the President, was overseer of all science research and developnent efforts related to the war. The Office of Scientific Research and Levelopnent, the principal coordinating mechanism, included as a very imf)Ortant component the Committee on Medical Research, presided over by Dr. A.N. Richards and included the Surgeons General of the Army and the Navy. Sitting in for the Surgeon General of the PUblic Health Service was the Assistant Surgeon General and Director of the National Institute of Health, Dr. Rolla Eugene Dyer. 11 CMR's assigned job was that of ''mobilizing the medical and scientific personnel of the nation" and "recomnending the need for and character of contracts to be entered into with universities, hospitals and other agencies conducting medical research activities ••• related to the national defense. 1112 To accomplish this task, CMR set up (with the help of the National Academy of Sciences and its National Research Council) fifty­ one committees and panels to review medical needs and scientific possibilities. Members of the comnittees also specifically reviewed proposed contracts and made judgments about their adequacy before the contracts were let. Altogether, in the years between 1941 and 1947, the corrmittee awarded some $25 million for 593 contracts for work carried out in 135 universities, hospitals, research institutions and industrial firms. Section II, page 2 () The whole effort involved approximately 1,700 medical doctors and 3,800 scientists and technologists. 13 Some of the contracts focused especially on battletime problems e.g. aviation medicine and even surgical procedures - but others encompassed broader research, including chemistry and physiology. In fact, many of the contracts were in areas in which the Public Health Service and the National Institute of Health had expended much of its money and energy in the preceding decade: malaria and yellow fever, syphilis and gonorrhea, mental health. The Committee on Medical Research obviously saw that the laboratory and field work of the 1930s was a boon to solving wartime medical threats: troops fighting in tropical climates multiplied opportunities for malarial agents to do their damage; millions of men in uniform flung across the globe multiplied the possibility of exposure to venereal diseases. Later, as the· conflict wound down, those same leaders, along with an increasing number of public officials and some of the citizenry, recognized that the wartime medical experience was translatable to civilian needs. Work on malaria had continued in-house at the NIH laboratories as well as under wartime contracts. By the end of the war, more than thirty effective chemical agents against malaria had been proven, a feat which some considered to have been a major benefit to the war effort in Asia. But the greatest advance in the treatment of a variety of medical problems was mass production and expanded use of penicillin. This occured at the height of the war in 1943. Soon it was demonstrated that penicillin not only counteracted infections in war wounds and other trauma, but essentially could cure pneumonia, syphilis, and a variety of other problems. Section II, page 3 Still, in his first postwar report on the Pubilc Health Service, Dr. Parran had to report that, in 1946, respiratory diseases, including influenza and pneumonia, were of epidemic proportion, with more than 68,000 deaths from those two maladies in that year. There ~re still more than half a million new cases of syphilis and gonorrhea being reported each year, but thanks largely to penicillin, syphilis deaths declinied from 14,000 in 1945 to less than 13,000 in 1946. There were almost 53,000 ) deaths from tuberculosis. Even smallpox, thought to have been permanently eliminated, in part because of the earlier work engaged in and supported by the Public Health Service, reared its ugly head again in 1946, resulting in 80 cases and 19 deaths. 14 Three threatening new problems anerged. The incidence of cancer had increased significantly over the preceding decade. Polio- myletis in 1946 reached its highest incidence - 25,000 cases reported in that year -­ since 1916, when the number reported was 30,000. Third: "There were 33,411 deaths from motor vehicle accidents in 1946, 19% more than in 1945.,J5-rhe ) end of the war meant the end of gasoline rationing, and more people driving more cars was soon to put motor vehicle accidents in the top rank of killers. '!he practical experience and specific progress from 1942 through 1945 brought about a new philosophical attitude toward goverrnnent's role in science and health and new optimism about the po~r of science, particularly organized science. The wartime medical administrators were themselves impressed when they compiled the list of practical results .which could now be put to use for the civilian population. Beyond penicillin, there had been breakthroughs in gamna globulin, adrenal steroids, cortisone Section II, page 4 and blood plasma. The public officials who listened to the recitation were a\4estruck.1 6 As Dr. Frederick Stone later put it, fran then on "science was spelled with a capital 'S' and research with a capital 'R'." 17 A specific bit of evidence of the broader optimism was that by August of 1944, the Corrmittee on Medical Research was already considering how, as the United States anerged victorious fran war, it might dissolve itself. Dr. Bush, and apparently President Truman, thought the Cormnittee if not the entire OSRD should stay in business indefinitely. It certainly._ should be kept in place at least until a new national science foundation (and perhaps an additional and separate national medical research foundation) could be created. Nonetheless, the CMR proceeded to consider alternatives to remaining operational. In August of 1944, after consultation with Surgeon General Parran, Dr. Dyer wrote to Dr. Richards to suggest that the Public Health Service, in light of its experience in a variety of grants-in-aid over the previous de­ cade and in cancer since 1937, had the requisite credentials to continue the wartime contracts if the Cormnittee wished it to. The letter and its pranise carried more weight in the context of recent legislative events. On July 1, 1944, the President had signed the PUblic Health Service Act (Public Law 78-410), basically formulated by Dr. Parran and Assistant Surgeon General L.R. Thanpson, which broadened and reemphasized the authority of the Surgeon General "to conduct and support research into the diseases and disabilities of man." To consolidate the research program, the National Cancer Institute was made a division of the National Institute! of Health, and the Surgeon General was anfX)wered to create new organizational entities to help carry out the renewed research mandate_l.8 An affirmative answer did not come automatically. Despite the consensus on the poW=r of science against disease and injury, and on the need for federal support of science in this role, there was very great diffusion of opinion as to how the government should appropriately continue in the arena of biomedical research. Dr. Bush preferred a comprehensive new national science foundation, a formal proposal for which he would draft 9 and the President would submit to Congress in 194sf Dr. Palmer and his comnittee, whom Bush had asked to review possibilities, preferred a separate foundation for medical research. The latter position was also favored by Senator Claude Pepper who chaired the wartime congressional Comnittee on Health and Etlucation. Of the many voices speaking to the question of how to proceed once hostilities ceased, only the Surgeon General of the Public Health Service and his NIH director urged that PHS/NIH simply take over this fun~tion by expanding its existing role and building on its earlier track record. There being no certainty about the direction of the transition from a short-term system of centralized support to a long-run, indeed open-ended program of government support for medical science, it is no wonder that there was some scientific and bureacratic in-fighting at the moment, as well as attention to it by political science specialists in later years. 20 F.specially in hindsight can we see what a stunning feat Dr. Parran and Dr. Dyer performed, through ingenuity and persistence, in moving from a modest existing program to "the building of a medical research anpire" by arranging the takeover ,of a handful of wartime research contracts and converting then into on-going grants. 21 The NIH grant-making experience was really more limited than they implied; and there was increasingly clear Section II, page 6 difference between the nature and implications of "grant" versus "contract". But on substance - malaria, venereal diseases - it was a natural transition and transfer. Much water floW=d under the bridge between the time of Dr. Dyer's letter to Or. Richards of August 1944 until the actual transfer of the contracts at the end of 1945. But on January 1, 1946, NIH found itself responsible for the administration of sixty-six contracts which more than tripled its budget and, more than anyone imagined at the time, positioned it to become the principal federal government vehicle for the performance and support of biomedical research for the forseeable future and beyond. ) III Ernest Allen was running a program for the National Youth Administra­ tion in Augusta, Georgia, when Pearl Harbor was bombed. The war effort overtook New Deal programs and the mobilization effort found spaces for people - students and professionals alike -- who had earlier been involved in the NYA. Indeed, the new national cause hastened the end of many of the "alphabet programs" launched by President Roosevelt to help pull the country out of the Great Depression. The termination of the particular NYA program in Augusta happened just about the same time as the expansion of the effort against venereal diseases. One day, young Mr. Allen received a visit from an important Public Health Service -officer, Dr. Cassius J. Van Slyke, who came to explore the possible conversion of a youth program facility into a V.D. treatment center. Dr. van Slyke was at that moment Assistant Chief of the ) Venereal Diseases Division of the Public Health Service. To assist in the transition, van Slyke asked Allen to join the Public Health Service and help take charge of the new program in the same old building. Dr. Allen agreed. The year was 1943. Two years later, Dr. Van Slyke had a heart attack. Some of his fellow officers, being concerned, tried to find him a position in the Service with fewer strains and burdens than running one of its larger programs. His friend and division boss, Rod Heller, heard that Dr. Dyer was looking for someone to look after the OSRD contracts. There could be nothing strenuous, it was thought, about overseeing 66 contracts, wor_th about $870,000, which ~re Section III, page 2 underway and were due to terminate in six months. But it could be novel, so perhaps Dr. Van Slyke might be willing to do the job. Van Slyke demurred. Through Heller, Dyer pressed him "as a brother officer to give him a hand in time of need." Besides, knowing what his doctor's orders were, he assured Van Slyke that he: •••positively wouldn't have to work more than two hours any day and probably not more than four or five hours a week [since] thi( was something that was just going to be turned off. 2 Far from being "just an incidental, part-time, lower-left-hand-drawer of the desk sort of activity," as envisioned, Van Slyke soon found himself putting in twelve to fourteen hours per day. He called his friend Ernest Allen and asked him to come to Washington to help. Early in 1946, with strong backing from Dr. Dyer, they set up the Office of Research Grants of the U.S. Public Health Service.· From that moment on, several equations changed. Dr. van Slyke began to see matters in a different light. For one thing, while all the contracts were officially to terminate on June 30, 1946, a number of them were of a continuing nature, and it was implicit that they could be extended further given the fact that the work in progress was productive and relevant to persistent national health problems. Dr. Dyer agreed to try to secure funds for the next fiscal year so that much of the "wartime work" could go on. There was one small problem: whereas there had been some discussion of NIH grant authority, neither the agency nor the parent Public Health Service had explicit authority to enter into contracts. Dr. Parran, a quintessential New Dealer who believed that government should take a large Section III, page 3 ) and active role in solving problems and coping with new situations, sailed over the questions of definition and of relevant statutory authorities by calling what had been received and was being overseen by NIH as "grant contracts. 1125 But Dr. Parran knew they were research grants, and he expected than, or others like or unlike than, to be continued. In his October 1946 report issued eight months after the "tan:i;x>rary contracts" were J transferred, he wrote: Under the research grants program, the Service has undertaken to continue many of the valuable medical investigations sponsored by the Office of Scientific ) Research.and r:evelopment during the war. The program is now being administered on a permanent peacetime basis, and non-military projects are increasing. 26 In fact, he and Dr. Dyer had already proposed a budget and secured appropriations for NIH for fisca_l year 1947 of $8 million, of which $4 million was for extramural grants. The National Cancer Institute, under authority given at its creation ) in 1937, had been making a few grants each year. Ernest Allen reviewed that program immediately upon arriving at NI~. He found that there were only a few grants in effect. They were being run out of the OCI director's J office with one lady, Ora Marashino, handling the "program" and with some involvement of ~e National Cancer Councii. 27 The review of grant proposals by the National Cancer Council was thus an established, if limited, tradition. The Council was made up exclusively of specialists in various aspects of cancer research and treatment, so its oversight was that of any group of experts. Similarly, the OSRD had had groups of scientists review contract ideas and proposals during the war 0 Section III, page 4 years. The NIH itself had handled its review process in earlier years in even more informal ways. Review of proposed NIH grants by the National .Advisory Health Council was not tantamount to expert review, for this Council included public health officers and health administrators as well as clinicians and a few bench scientists. Thus one of the first questions Van Slyke and Allen pondered in 1946 was how to insure that, if the grants program should continue and grow, quality remained high and scientific bets more sure. The scientific review question, obviously important, also became urgent. The price of penicillin fell sharply at the point that mass ,J production of it became possible in 1946. Consequently, expenditures for the existing contracts were reduced, leaving a residual sum of some thousands of dollars which could be used to support other research. van Slyke and Allen composed and sent out what Dr. Allen later called "the most naive letter ever to emanate from the national government in Washington." It was addressed to the deans of all medical schools in the United States and conveyed the following brief message: "We have limited funds available for research purposes. If you have investigators who need these funds, let us hear by return mail." iB The shedding of uniforms in 1945 and 1946 was as rapid and extensive as the donning of them in 1941 and 1942. By the time the van Slyke/Allen letter reached the medical school deans, scores of scientists were back at their desks and in their laboratories, brimning with ideas but having only scant resources. The response to the letter was overwhelming. The grants office - the two professionals and their two secretaries -- called their friends to ask for help. They even procured a copy of Men of Science to Section III, page 5 C) try to identify people working in the same areas as the person for whom the C) institutions sent the applications. "We would write to three or four of these people and get their opinions on the merit of the proposal. We then took the proposals to the National .Advisory Health Council." 29 That specific and immediate response, of course, took place in the larger context of nationwide enthusiasm for the accomplishments of wartime science. Further, new problems had been identified, importantly included 0 among them widespread mental disorders uncovered in the course of examinations of inductees and, soon after the war's end, behavioral problems of returning veterans. The overall situation was described by Dr. Parran in his annual report to the Congress: This year of reconversion has been a time of unprecedented public interest in the health problems of the nation. Free from the tasks of war, we and .America have once again turned our attention to the more. fruitful tasks of peace. Having preserved freedom, we are more than ever determined to use that freedom to make our country a better place in which to live. High among the goals which we have set for ourselves in the coming years is the improvanent of our national health. This new concern with problems of health springs from many sources. In part, it is the result of the conditions revealed by selective service examinations. In part, due to dramatic advances made in certain fields of medical science in recent years. Another factor is the experience of our service men and wanen, millions of whom have known, for the first time, the benefits of comprehensive medical care and preventive medicine. They have returned home with new concepts 8f what can and should be accomplished in their conmunities. 3 Given the general enthusiasm and the specific invitation to apply for grants, it should not have been surprising that the response was so heavy. Within a year, more than a thousand applications had been received. From January 1946, when the contracts were added, through August 31, 1947, Section III, page 6 $10 million was paid to scientists working in non-governmental institu­ tions. The ad hoc procedures used in that first year would clearly not be sufficient for the future. For one thing, the half-dozen review groups focusing on traditional PHS concerns - malaria, tuberculosis, hygiene, venereal disease, biology and pathology - would have to be expanded in number and in fields covered. A second round of letters was sent out by the Office of Research Grants, asking distinguished men and women of science if they would serve for a specified time on "study sections" to review grant proposals in imp::>rtant fields. By the end of the year, t'Aenty-one study sections had been established, peopled by scientists from universities, medical schools and research institutions, with a few additional ones from other government agencies. Dr. van Slyke was pleased to report that, within a year, ''more than 250 leading scientists" were guiding the study sections •31 Also by the end of that year, the operations of the (newly named) Division of Research Grants had been extended to include the administration of the extramural research grant programs of the National Cancer Institute and the Division of Mental Hygiene (later the National Institute of Mental Health). Wlen Dr. John D. Porterfield and Dr. David E. Price joined the Division that year, the professional staff doubled. As they reviewed that first year's activities, the most striking aspect of it was that many more grant applications \\ere coming in than there was money to support. Dr. Van Slyke and his team reported to the Surgeon G:neral that considerably more funds could be used the following Section III, page 7 year and urged him to seek increases. It was a recommendation that the broad-visioned Tom Parran readily e:nbraced. It was he, after all, in his first year as Surgeon Ceneral, 1936, who had specified seventy research areas that he wished NIH to explore if it had the funds and the authority. Thus, the report of his research grants team in 1946 permitted him to call for "new programs to anerge from the blueprint stage," particularly programs in mental illness, heart disease, dental caries, and chronic diseases of old age.32 Like Tom Parran, Cassius J. van Slyke was also a man of enormous energy and broad reach. Dr. Allen confirms that, from an early point, Dr. Van Slyke saw an opportunity for good and for growth, an opportunity and spirit which Allen, as a novice in the field of bianedical research, came quickly to share. But no one seaned to realize that the new era was to be one of unlimited expansion and unthinkably large research budgets. Dr. Endicott, who joined the grants division in 1948, rananbers asking Dr. Dyer where he thought the program would level off. Dr. Dyer responded: "It will plateau at about $25 million.,.3 3 As it turned out, the $25 million level was reached within two years. Dr. Dyer had not fully understood the vision and the vigor of his deputy Dr. Van Slyke at the point that he made that prediction. Later, when he had taken full measure of the man he had brought to work for NIH in that undananding, possibly part-time job, he asked an interviewer if he had known C.J. van Slyke •., The response was negative. Said Dr. Dyer, "you've never seen anything like him. 1134 IV '!he more than 250 scientists recruited to serve on study sections in 1946 had as counterparts a slightly larger cadre of scientists working in the in-house laboratories of NIH in the early years after the war. Dr. Endicott believed the number to have been about 300. In their collective work, these goverrnnent scientists spanned all those areas in which study sections for the review of extramural awards had been created. So it was natural that intramural scientists would be asked to help to shepherd along study sections in their special fields. In the first couple of years, the executive secretaries -- administrative officers - of the study sections were NIH researchers, while the chairmen were distinguished scientists in universities, medical schools, or in some cases, industry. Study sections met quarterly, usually a few weeks in advance of the quarterly meeting of the National Advisory Health Council and the National cancer Council, and recommended to the councils whether or not a proposed research project application "is acceptable and can be supported by research grant funds. •~35 From the first, study section chairmen and the executive secretaries were very important figures in their fields or in NIH. Dr. van Slyke himself was the first executive secretary of the antibiotics study section (and four others); its chairman was Dr. Hans T. Clarke of Columbia University. Other"eninent figures who chaired study sections were: Dr. E. Coles Andress of Johns Hopkins University, cardiovascular; Dr. Carls. Schmidt of the University of Pennsylvania, pharmacology; Dr. Andrew Warren of the Rockefeller Foundation, tropical diseases study section; Dr. John R. Paul of Yale, virus and rickettsial Section IV, page 2 diseases; and Dr. James A. Shannon, Squibb Institute for Medical Research, malaria. Other executive secretaries from NIH included: Dr. Trendly Dean, later to become pirector of the National Institute of Dental Health, dental research; Dr. Endicott, hernotology, and later Director of the National cancer Institute; and Dr. Norman Topping, who would shortly become Surgeon General of the PUblic Health Service, viruses and rickettsial diseases. Two concerns follo\Ed the rapid expansion of applications, study sections, and study section meetings. The first was simply the amount of time study section membership and administration increasingly took. Neither administrators like ors. Van Slyke, Price, Endicott, Dean, and Topping, nor working scientists from the intramural program could keep pace with the ever heavier load and still do their principal jobs well. In fact when the study sections were first created, van Slyke and Allen had a hard time getting NIH scientists to serve·as executive secretaries. "They considered this as a passing sort of thing, this 'give away' program. ,3 6 So van Slyke served as "exec. sec." to five study sections in the early months. That attitude soon changed, ho\Ever, and a second concern arose: that asking working scientists at NIH to oversee study section activity might lead thern into the ternptation of exerting undue influence, even if unconsciously, on directions to be taken in their own fields, leading to perceptions of conflict-of-interest. Dr. David Price, who became the third man in the Office of Research Grants just after Dr. van Slyke and Mr. Allen began it, recalled: One of the things that we were always sensitive about, and Dr. Dyer felt very strongly about, was that the grants program ought not to be run by the intramural scientists at the NIH. That was of course the obvious, easy way to go because the program at that point was small and it would have been manageable to have the scientific review done by intramural scientists. But we Section IV, page 3 realized that to do that would place the program in some jeopardy, with people feeling that· their ideas were being "stolen" by government scientists. We wanted to keep any accu~ation ~f that ~jnd from occuring, so we chose to use outside reviewers. A decision was taken to recruit, from outside NIH, scientists and other qualified persons to be permanent, full-time executive secretaries. As Dr. Dale Lindsay has recorded in his monograph on the history, organization and functions of the Division of Research Grants: "By the end of 1948, it was recognized that the office of executive secretary of a study section was a full-time responsibility. Qualified scientists were therefore invited to accept appointments as executive secretaries of the DRG staff.h The responsibility of the study sections, specified by Dr. van Slyke, was two-fold: (1) to review applications for research grants in their respec­ tive fields, approving than, suggesting changes or further study, or disapproving than, and forwarding their reccmnenda­ tions to the appropriate National Advisory Councils; and (2) as scientific leaders, to survey the status of research in their fields in order to discern neglected areas in which research is· particularly wanting, and to stimulate the interest in workers competent to undertake needed research.38 The apparatus being put in place for the administration of research grants was carefully instructed on some very specific principles and convictions. One thing that had especially bothered Dr. van Slyke about the wartime contracts was that they required a lot of paperwork - quar­ terly reports on the science itself plus quarterly financial statements. In his first review of the new program he wrote: "In order not to divert the time of the researcher unnecessarily from the actual conduct of research investigation, only ar,mual scientific progress reports are reque~ted." t-t>r, he added, is it "desired that the preparation of these reports present any long, tedious burden to the investigator" They should simply "contain Section IV, page 4 only such data in a brief, clear and concise manner which would permit the appropriate study section and national advisory council to "be in a posi­ tion to endorse the grant as it comes up for renewal annually." Henceforth grantees would simply be required to submit "simple financial reports to show current status of funds •• twice each year. 11 39 The bedrock principle asserted and reiterated from 1946 onward was that the U.S. PUblic Health Service research grants program was to be "a medical .research program of scientists and by scientists." The basic tenet of the philosophy upon which the program and the scientific method rested, said Dr. Van Slyke, was "the integrity and independence of the research worker and his freedom from control, direction, regimentation and outside interference.'' 4o No one denied the efficacy of organized research, focused on targeted directives and even centrally directed, for a short period of time, as in the duration of a four-year war. The proble:n with that approach for peacetime purposes, suggested Dr. van Slyke, was that "promising bypaths often had to be bypassed. 11 41 What was needed for the long term, the NIH leaders ~re convinced, was an unloosing of scientific curiosity and exploration, giving researchers free reign to pursue inqiries and studies JD they thought important. Dr • Dyer put it once thus: Once the scene shifts from the anergency, ••• anphasis is placed not upon the goa..1, but upon the scientist pursuing his interest as Wtinct from bureaucratic control over those interests. Every leader of every Institute, division and office of NIH was inculcated with the same belief. It ws held more fervently than a typical Part 4, page 5 philosophy might be. Dr • Robert Felix, who oversaw the developnent of the National Institute of Mental Health and its transmogrification from the old Division of Mental Hygiene, put the conviction in perhaps the aptest terms: "It is a fundamental tenet of our 'religion' here that research must be free and researchers must be free •11 43 In the new period of expansion, what was needed was unity of guiding principles and consolidation of administrative practice. The National Cancer Institutes had become a division of the National Institutes of Health under the 1944 PHS statutory revisions. Beyond the formality of the organizational relationship, the personal relationship between the directors, Dr. Dyer of NIH and Dr. Roscoe Spencer of NCI, must have been cordial and cooperative, as there is evidence of considerable cooperation and interchange between the two entities. Soon after Dr. David price was trained in the philosophy and practice of grants administration at NIH, he was assigned to the National Cancer Institute as director of its grants program. Dr. Price formally organized the Office of Research Grants in the Cancer Institute and set about instituting policies and procedures similar to those at NIH. One of the first persons he asked to help in the new endeavor was Dr. Ralph Meader, a faculty manber in the Department of Anatomy at the Yale Medical School who, during the war, had taken over administration of the Jane Coffin Childs Manorial Fund, administered through Yale and focused on cancer research. As Dr. Price surranarizes it: "This gave Ralph contacts in the cancer research field .that were rather unique. So we got him to work with me part time to help introduce me around, open doors for me, and help peddle the federal money. 11 44 Section IV, page 6 Having pursuaded Dr. Meader to come full time to ~I, Dr. Price then J moved back to NIH as the director of the Division of Research Grants in 1948 when Dr. van Slyke was appointed director of the newly created National Heart Institute. Changes and expansion were the NIH reality from then on, but Dr. Meader never forgot the basis on which·the aggregate program was formed and continued to operate. He later wrote: "'!he administration of the research grants program has been designed and modified, as needed, to support competent investigators, to sustain the broad concept of relevance to disease, and to give the investigator maximum freedom. 1145 ribe Division of Research Grants had had two and a half years of experience before the big boom started. In the stmner of 1948, Congress passed and the President signed the National Heart Act, which authorized the National Heart Institute and.changed the name of the National Institute of Health to National Institutes of Health. Under discretionary authority, the National Institute of Dental Research was established in September and ) the National Microbiological Institute and the Experimental Biology and Medicine Institute on November 1. Dr. van Slyke became the first director of the Heart Institute and just about the same time, his old friend and ) colleague, or. Roderick Heller became director of the National Cancer Institute. With ors. Allen, Price and Endicott at the Division of Research Grants, and Dr. Meader with Dr. Heller at OCI, a team and a unified systan of grantmaking was in place. In these first years, men and women of talent were placed in novel positions in new organizations, and were drawn from a variety of situations. But those first appointed to NIH leadership posts came Section IV, page 7 directly from the Public Health Service, a fact which must have contributed ) much to the cooperation, cohesion and c<lmaraderie of the early years. It was by no means a closed club. In addition to Dr. Meader, Dr. Arthritis Ralph Knutti was soon recruited to the <: ~"' rnsti tute from the University Southern of California. Dr. Frederick Stone, the recent acquirer of a Ph.D. degree in biology and a commission in the U.S. Marine Corps, was recruited directly by Dr. van Slyke from the University of Rochester. Dr. J. Franklin Yeager, a specialist in insect physiology, was invited to come to NIH from the D=partrnent of Agriculture's research center in Beltsville, Maryland. While most of the study section exec. secs. had formal training and many had earned doctorals, others did not. Olive Meader, who for years had worked beside her husband Ralph in laboratories and other research environnents but had no degree in science, was known as a very excellent executive secretary of special studies. There were others - both men and wanen -- like her. Ernest Allen, the former French teacher, must have made sure that talent and experience were not denied for lack of formal degrees. The new NIH recruits were chosen for their scientific knowledge and experience, or their leadership in the field in public health or military medicine, or their administrative capacity, or any combination of these. But it was quite clear that grants administration was to be a major part, and a crucial one, of the new enterprise. And so when administrative experience could not be found extant, it would have to be learned. Dr. Stone remenbers clear1y and vividly his first conversation with Ernest Allen in 1948. "Administration is a discipline just like science is," said _) Section IV, page 8 Dr. Allen: "To learn it, you have to start from the ground up, so you will begin by taking travel requests and expense accounts just like the young laboratory assistant has to wash bottles. 11 46 But, in typical Allen fashion, he also assured the young man that, because he had recently been a graduate student, he could help the Division of Research Grants greatly in making sure the proposed research fellowships and traineeships, which the Division was developing and would administer, accorded with realities. Thus the building of a cadre of experienced personnel went in two directions, deep into the PUblic Health Service tradition of career ) officers, many with research specialties but most who were broad-based and flexible, and out into the newly strenghthened, ready-to-blossom academic centers across the land. The movanent of key persons between Institutes helped to insure conmon experience and unanimity of purpose just as congressional and public enthusiasm for research inspired excitanent. By 1950, the team was in place, the premises -were established, the purposes ) rolled easily off all administrators' tongues; the system was ready and rolling. And it was a very good thing, for in that year Congress passed the Qnnibus Medical Research Act authorizing two new institutes - the National Institute of Neurological Diseases and Blindness and the National Institute of Arthritic and Metabolic Diseases (absorbing the Experimental Biology and Medicine Institute) -- and giving the Surgeon General the authority to establish still other institutes as the need and opportunity dictated. The stage was set for the greatest period of biomedical research growth in the nation's history. V Freedom for the scientist might theoretically have implied passivity on the part of the bureaucracy. But the pattern that soon developed was much too activist for that description. In fact, it was downright entrepreneurial. With ever-increasing flurries of activity - new institutes, new areas of exploration and support, and new study sections to accomodate then -- there was increasing need for direct corcmunication between the scientific community, dispersed as it was in most parts of the country, and the National Institutes of Health. Every early action of an NIH leader -- a merely descriptive article in Science by Dr. van Slyke; a simple visit by Dr. Allen to explain a particular program or ask a particular scientist for his help in reviewing it; a responsive call by Dr. Price to a university whose scientists or administrators seemed confused as to how grants were made - was used as a precedent and a building block. Soon all the key players from Bethesda - Institute directors, heads of the Division of Research Grants, and executive secretaries of study sections were writing articles, visiting schools, making talks. If this business had been formalized, "dissemination of information" and "constituency relations" would have been an explicit part of every bureaucrat's job description. Dr. Allen recalled that especially if he received a critical letter about the grants program from a scientist of any importance, he immediately went to see him to explain the new program and, often to get the scientist involved in a study section as well as interested in grant possibilities. Franklin Yeager recalled: "When I went to the Heart Institute in 1948, one Section v, page 2 J of the first jobs that van Slyke had me do there was spread knowledge of the NIH programs around the United States, visit the universities and medical schools and talk up the grants program ••• I spent several weeks visiting various institutions all up and down the West Coast, and applications came in as a result. 11 47 Fred Stone sunmed it up: IIIt wasn't anything to travel 200,000 miles in a year. 11 48 Reports on what grants were made to which institutions for what particular purposes were submitted not just to the Surgeon General and, in turn, to Congress, but were being publicized in a variety of rnedia. To make sure people understood that the National Cancer Institute not only made research awards but also research facilities grants, Dr. Meader and his colleague W.W. Payne described than in a 1951 article circulated to all ) public and private state and local agencies and institutions having any connection with public health activities. It was absolutely factual in is detail, and it must have been, to any administrator who didn't know about the construction grants, an open invitation to apply for one. The authors encapsulated the origins and purposes of the grants as follows: Secular wartime progress in research had quickened public interest in cancer and encouraged the popular hope that cancer might be conquered. The result, following World War II, was an unprecedented increase in funds for research projects and research training ••• Ho~ver, nationwide expansion of cancer research was slowed by the lack of facilities. To ranove this bottleneck to further expansion and provide laboratory space for housing new studies of cancer and utilizing the enlarged force of scientists, Congress authorized the cance\ research facilities construction grants program. 9 The explicit criteria for awarding the grants were two: "Cne indicated Section v, page 3 that the funds should go to a few large institutions with well established medical research programs. The other indicated the aid should go to strengthen smaller institutions with limited. research resources." Three other factors were involved: most of the grantee institutions agreed and demonstrated a capacity to "contribute a large proportion of construction costs;" they assured continued support to research programs to be conducted in the facilities; and they were actively cooperating in the develo:pnent of the State cancer control program. Those making the awards cle~rly had geographical distribution in mind. They proudly pointed out that "all of the nine United States census regions are represented among the grantees.n.50 ) To tout the availability of research grants in sanitary engineering, Irving G:rring, executive secretary of the responsible study section, wrote a special article for the journal of the .American Waterworks Association that was even more solicitous and obvious. He and his superiors were concerned that this particular program had not gro-wn very much in a decade since its establishment, and so he wrote: "In proportion to its imi;x:>rtance, research in water control activities from the viewpoint of developing fundamental knowledge has made little advance, at least in this program. 11 • 51 He spelled out the criteria for grants and more or less urged that grant requests be sul:mitted. And he paid honmage to the other guiding principal of the DRG, writing: "Such proposals in almost all instances will reflect the initiative and originality of the investigator." 52 Council chairmen and members, Institute directors, other study section executive secretaries and members - almost everyone involved in the grants program -- wrote similar articles. Ernest Allen even wrote one explaining why some research grants proposals were turned do-wn, thus illuminating the Section V, page 4 path to more successful applications. 53 Another means of encouraging expanded scientific activity, in parti­ cular directions and special fields, was to convene meetings. Morris Graff, an endocrinologist who was a study section executive secretary for more than twenty years beginning in 1950, described the situation in which members of study sections would initiate inquiries about "areas where they would want to educate their colleagues in what was going on in research in a new area." The study section, in response, would often organize workships, and pay for them, inviting a handful of known experts. These workshops would, in turn, often lead to larger conferences to which an open invitation was issued. 54 Dr. Irving Fuhr, another long-time exec. sec., specified such an instance in the 1950s. He had invited Dr. F.O. Schmidt of M.I.T. to meet with the National .Advisory Health Council and describe informally recent advances and new possibilities in biophysics and biophysical chemistry. Council member Mary (Mrs. Nelson) Rockefeller was impressed; at her suggestion the Council made a grant to the biophysics and biophysical chemistry study section so that the study section could organize a national - 55 conference to publicize these recent developments and continuing needs. The Division of Research Grants was as entreprenneurial as the "categor­ ical institutes." Through the 1950s it had the responsibility and the funds to make sure that no important fields were left completely uncovered. The program officers, the study section chairman and members, the executive secretaries - all from time to time proposed particular initiatives. But the DRG leaders and the executive secretaries were often the most active. They, after all, could recorrmend the creation of new study sections, or Section v, page 5 II II issue Requests for Proposals in particular fields. It was fran Ernest Allen and his DRG collaborators that Fred Stone says he learned entrepreneurial as well as administrative skills. He recalled an example used more than once when a specific research need was identified: You create a study section and give a chairman's grant and you have a heart-to-heart talk with the chairman and the study section to tell than you are convinced that this field needs stimulation. It's an important field, and it ought to be developed, so go out and do it. 56 ) VI. The crucial feat of every living creature, whether individual or institution, is to maintain balance while experiencing growth. In the case of the National Institutes of Health, many balance wheels had to be maintained at the same time: assuring the complementary nature of the intramural and extramural programs; rraintaining freedom of initiative for scientists and responsiveness to public needs and concerns; keeping fiscal and reporting requirements from being onerous to the investigator while guaranteeing that public funds were appropriately used; supporting research excellence wherever it existed and encouraging the growth of new centers of potential excellence; investing in established scientists and tested methods while not ignoring innovators and innovations. To cover several of these balancing needs in a systematic way, the ) pioneers of the grants program quickly added a second step to the first one of expert review - program review. Once a grant proposal was approved by a study section, with the proposed research and the scientist responsible rated important and sound by peers, the Division of Research Grants assigned the proposed project tb a particular Institute. with whose mission and pro­ gramnatic scope its content and purpose best matched. The entire proposal, plus a surrmary sheet written by the executive secretary of the study section recomnending it, was provided to manbers of the advisory council Section VI, page 2 of the Institute and reviewed at one of the council's quarterly meetings. In those years, councils spent considerable time discussing individual applications, their relevance to the Institute's interest being assumed. Some were deaned by the council to be more important to particular priorities than others, and so that factor, in addition to the grade score provided by the study section, could cause a reordering of overall scores. In more recent years, the surrmary sheets are considerably more elaborate and individual applications thenselves are rarely read, dissected and discussed by the council. In contrast to the 1950s, in the 1980s the councils move from the general to the particular. They help establish overall needs and program priorities, then fit proposals into that hierarchy of values and needs. Both the increased complexity of science and the much larger volume of proposals have necessitated this evolution. J But the principle of review for program relevance remains established and operationally viable. Other balancing acts have been harder to maintain on the basis of a single principle or operational mode. From its very beginnings, NIH had the authority to award fellowships. Before 1946, it had done so in the same way and at roughly the same level as its research grants. Ernest Allen discovered in his early days at NIH that the small fellowship program was run by the Assistant Director of NIH, Lucius Badget. There being only a few applicants annually for such fellowships, Mr. Badget reviewed the applications himself and made the decisions as to who should get then, subject to Dr. Dyer's approval. The Division of Research Grants then took 1J Section VI, page 3 over, and the fellowship program grew steadily, although never as rapidly as the grants program.57 Dr. Van Slyke recognized full well that to build a national biomedical science research base, more young scientists needed to be encouraged and trained. But he fretted about making individual decisions about individual potential researchers. This was doing business "retail" when what was needed was a wholesale approach. Fred Stone discovered another problem. The way the fellowship program was actually working in 1948 was that NIH Fellows were being used simply as research assistants, as extra pairs of hands, as cheap labor. But how to get around this problem without thoroughly offending senior scientists in eminent institutions? It had to be done though: "A fellowship was not intended to give the recipient an opportunity to shoulder half the teaching _load of the department, but it was given so that within a normal period of time you could get your degree ••• and carry on the research after your degree in the same or other departments, or in the same or other institutions." 58 over a three year period, the criteria for fellowships were changed and strenghtened: the reasserted purpose was to support _) post-doctoral work for M.D.s and doctoral or postdoctoral work for Ph.D.s, and a four-year maximum was established for fellowships. Under the refined rules, a Fellow could not remain a junior sidekick to a senior scientist for an indefinite leng1;h of time. With these amendments, the fellowship program grew from "a few tens of thousands of dollars" in 1948 "to perhaps 59 $600-700,000 in 1952." 0 0 Section VJ., page 4 But the effort to support the training of new researchers was still a J matter of individual selection and individual review. What was needed was a system for deciding on need, relevance and quality in a way that recognized strengths and needs of institutions as well as of individuals, J and which in fact was judged by institutions and not by bureaucrats. Dr. van Slyke proposed training grants as the answer. As Dr. Jerome Green recalls the story, van Slyke put it this way: "If we decide that the ) University of Chicago is a superb place to train pediatric cardiologists, and if we decide that the nation needs pediatric cardiologists, let's give the University of Chicago a grant based on stipends for individuals. Then they'll select the individuals. 1160 But training grants also included some money for the faculty, funds for the purchase of equipment, laboratory animals and some funds to pay the trainers as well as the trainees. J I There was yet another resource considered essential to the building of a national biomedical research capacity: adequate, up-to-date facilities. The National Cancer Institute was the first of the National Institutes of Health to award construction grants. It first did so, as Dr. Ralph Meader has recorded it, with line item appropriations for specific projects in appropriations bills beginning in 1947 (fiscal year 1948)~ 1 One of the first grants was an anergency award to help rebuild the Roscoe B. Jackson Manorial Laboratory in Bar Harbor, Maine, an important center of reserach on genetics and other factors in the causation of cancer, which was destroyed by fire. The more general pressure was the same that produced ~ increases in research grants and fellowships and training grants: "The nationwide expansion of cancer research was slowed by a lack of physical facilities." 62 When the National Heart Institute was created in 1948, it 0 Section VI, page 5 J was given specific authority to award grants for facilities, and in 1950 the National Cancer Institute was given similar authority. NCI moved swiftly to anploy the authority and within a year had awarded 63 grants in 0 aid totalling over $16 million.63 In the mid-'50s, as growth accelerated rapidly, NIH and its component institutes brought back another venerable research support mechanism, the 0 contract. At first, the contract mechanism was used in small ways and in snall amounts, for the purchase of equipment, for research animals, or to recruit a particular scientists for a particular mission. Dr. Ralph Knutti, who joined NIH in 1952 as Chief of the Extramural Programs of the new Arthritis and Metabolic Disease Institute and later became Director of the National Heart Institute, remembers both an early instance of a contract and later, larger examp~es. The earlier example was a contract with Dr. Hellen Tussig of The Johns Hopkins University who was conmissioned to travel to <::;ermany to investigate the thalidomide tragedy. Her on-site examination and official report cost only a few thousand dollars and resulted in stopping the use of thalidomide in the United States. Later, the National Heart Institute resorted to using the contract frequently and in substantial ways in connection with the launching of the artificial heart program. In this instance, contracts were used in a variety of ways, from agreanents with an outside group to organize an important advisory 0 caamittee meeting to "the payment for specific areas of investigation relative to the production of an implantable heart." 64 The urgency of another new program, the cancer chenotherapy program, prompted its director, Kenneth Endicott, in 1955, to secure specific congressional approval of the use of contracts. It was an altogether Section VI, page 6 appropriate request since it was Congress which, by and large, was putting pressure on tCI for an engineer-directed program in the cancer chemotherapy field. Dr. Dyer's successor, Dr. Henry Sebren, had asked Dr. Endicott to take charge of the chemotherapy program. The assignment was a tough one, Dr. Endicott recalled, because some saw the program as being more "developnent" than "research," and many thought that was not a role NIH and its com}?Onent institutes should undertake. Dr. Endicott made accepting the assignment dependent on being given authority to make contracts. His insistence stemmed from having had responsibility during the Korean War for NIH's program in research and developnent in the field of blood and blood substitutes, when "it was like pulling hen's teeth" to get the necessary com}?Onents of an overall research and developnent plan through the study . 65 sec.ions. t Even with new and specific authority to make contracts, Dr. Endicott knew the proposed work and the proposed contracts must be approved by peers if they were to be accepted in the scientific comnunity and in the department, where "there was a lot anxiety about it." In the chemotherapy program when we started off, I appointed the equivalent of study sections in screening, pharmacology, clinical trials and so on. The staff and these committees decided what it was we needed done, got out requests fo:r;, proposals and those same corcmittees reviewed than then. 06 Problems arose, ho\Ever, because most of the outside advisors on the chemotherapy program were also consultants to pharmaceutical companies, leading to clear possibilities of conflicts of interest. Dr. Endicott then abolished the external conmittees and used intramural corcmittees made up of NIH scientists to review contracts. What e:nerges from a review of the panoply of instruments the National Section VI, page 7 Institues of Health used in support of biomedical research is that whereas the individual project grants the investigator-initiated proposals -- were living, continuing proof of the goverrnnent's belief in the freedom of scientific investigation, the other means of support reflected other attitudes that were more directive and driving. The National Cancer Institute, the National Heart Institute, the National Institute of Mental Health were among the most dynamic in asserting priorities and assuming initiatives, but there were other examples as well. Soon after its establishment, the new Institute for Neurological Diseases and Stroke created a nationwide neurological training grant program because a quick review had shown that there were very few full-time neurological medical faculty in all of the United States, a condition that rendered research in neurology virtually impossible. In similar fashion, for example, direct stimulus was given the fields of·biophysics and molecular biology. Nonetheless, the use of grants has remained the principal, as well as the most revered approach from 1947 to the present day. By far the great bulk of awards has been to individual researchers who applied for grants; by far the greatest amount of dollars NIH invests in biomedical research is through research grants. Still, from the beginning to the present, the idea and practice of supporting individual researchers has been balanced with the need to build support systans. So while the pioneers and their successors had firm principles and, usually, clear priorities, they knew that their success in maintaining all the right bal~nces depended on, more than anything else, flexibility. Dr. Martin CUnmings, while serving as NIH Associate Director for Research Grant~ remembers a difficult question that arose in 1963. The J Section VI , page 8 ) National Library of Medicine applied to the National Heart Institute, through the DRG, for a grant to develop a computerized information system called "MEDLARS". The appropriate study section had approved it, as had the National Heart Council, but somewhere along the line someone raised the question: "How can part of NIH make a grant to its sister agency?" He consulted an old friend and an old hand: I called Ernest Allen [at that time, Deputy Assistant Secretary of HEW for Grants Policy] and said, 'I've got this thing here; it's a judgment call and I can't find any prededent for it"".' Ernest reminded me: 'Oh, there is a precedent. NIH, through an arrangement you and I made a long time ago, makes grants to Veterans Administration investigators ••• If we can give grants to people at the VA, why can't we give grants to people at the Library?' 67 'Ihus the National Library of Medicine got its first computer systan through a grant fran the National Heart Institute. Perhaps NIH flexibility in making unusual grants was partially inspired by the importance of some it had received. Dr. Currmings later discovered that the planning money for the National Library of Medicine's proposec:l computer-based bibliographic systan had been awarded to the Library, in a grant of $50,000, by the Council on Library Resources. 68 Another outside grant was recalled~- indeed never forgotten -- by Dr. Robert Felix. Th~ old PUblic Health Service Division of Mental Hygiene was converted into the National Institute of Mental Health by a statute in 1946. As director, Dr. Felix wanted to call a meeting of the National .Advisory Mental Health Council, but Congress had failed to make an appropriation for the new Institute and so it had no money. or. Felix made his plight known to a small foundation, the Greentree Foundation. They responded favorably, and with the grant, Dr. Felix called, and paid Section VI, page 9 0 for, the first Advisory Council meeting. He is probably still shaking his head: It has always been interesting to me that this Institute has given away hundreds of millions of dollars, but we got started with a grant fran the Greentree Foundation for $15,000. Later we rounded off numbers bigger than that. 69 ) VII Parallel with the establishment of the Division of Research Grants of NIH, the formulation of its policies and the consolidation of its administrative structure, debate continued as to the need for a national science foundation. The debate was finally resolved in the National Science Foundation Act, signed by President Truman in May 1950. The NSF was to include a Division of Biological and Medical Sciences. The same year Congress passed the Qnnibus Medical Research Act adding to NIH the Institute of Neurological Diseases and Blindness and the Institute of Arthritis and Metabolic Diseases, and further giving the Surgeon General authority to establish additional institutes as he determined the need for them. The emphasis of the National Science Foundation's medical research program was on "advancing our knowledge and understanding of biological and medical fields." NIH, it was stressed, "conducted and supported research aimed at the care and cure of diseases, including basic research." ?O Obviously, the delineation between function and responsibility was not crystal clear. By that time, NIH had a track record, a systen in place that was accepted and respected. Still, there was some apprehension on the part of PHS/NIH officers as to what the impact of the new National Science Founda­ tion would be on the NIH program. Even Dr. Van Slyke admitted: "We weren't sure what the National Science Foundation would do." The NIH attitude towards NSF was: "If you want to get funds and do the same thing and leave scientists free, that's fine with us, but that isn't going to stop us Section VII, page 2 C) because we don't know what you're going to do." van Slyke concluded: "I met some of those folks and talked with them afterwards, which made me feel pretty well justified that we hadn't stopped promoting our program. 11 71 Two years later, however, van Slyke and his colleagues were more confident: I felt that by this time it was so well established that nobody would ever dare to change this type of an approach for the support of science. It wasn't a question of the Public Health Service being the big shot in this thing. It was a question of, 'Does the scientist get his support without bureaucratic meddling?' That was the whole thing, and by 1952 ••• our program was six years old [and] I wouldn't have felt at all uneasy if our staff of people who knew how to run this thing had been put in some other agency to run it,. something separate from the Public Health Service because they couldn't possibly have changed it. 'Ulerewould have been such an uprising in the scientific community that they could have never gotten away with changing it.·72 So the NIH extramural program kept building. By 1955 (fiscal year 1956) NIH had an appropriation o~ $81 million, of which $54 million was awarded in grants for research, fellowship, training, and research facilities. These grants were awarded through the eight Institutes of NIH. Yet in that same year, an extraordinary challenge to the extramural program occured. In the middle of January 1955 the first Secretary of Health, Education and Welfare, Mrs. OVeta Culp Hobby, who had been comnander of the WACS during World War II, wrote a letter to the president of the National Academy of Sciences and asked that the academy undertake a review of all the Department's research activities, particularly the medical research component. secretary Hobby suggested that the NAS evalutation include the following elements: Consideration of the rate of growth of the programs of the Institutes of Health and other research units of the Public Health Service. In light of the responsibilities of the federal Section VII, page 3 government with respect to health, medical and related research; a general appraisal of the present level of support of medical research by this department; careful consideration of the proper balance of effort with respect to the support of basic research and research aimed more directly at the prevention, diagnosis, and care of current disease, and the relative distribution of effort among the major special fields of health research.73 In response, Dr. Alan Waterman cautioned that in view of the short time period Mrs. Hobby had proposed for the report ~r "desire for an early review" that "interim observations will of necessity have to be somewhat limited in scope and validity." 74 'Ihe Secretary's January request and the NAS president's February response were the first steps in the undertaking, and the only ones for six months. The organization of a special NAS conni ttee was not completed until July 1955. It held its first meeting on JUly 22. The Academy had asked the ccmnittee to submit its report in time for the annual meeting of the National Science Board in December 1955, further reducing the time available to the comnittee. Meanwhile, Secretary Hobby had resigned in the sumner of 1955 and Marion Folsom of the Kodak Corporation had become Secretary of HE.W. The special Committee on Medical Research of the NAS was chaired by Dr. C.N.H. Long, former r:ean of Yale Medical School. It included Dr. A. Baird Hasting of Harvard who had been a long-time member of the :National .Advisory Health Council; Dr. Charles B. Huggins of the University of Chicago; Colin r-tLeod, another distinguished physician, and Wendell Stanley, a distin­ guished researcher. Other members were Edward A. Doisy,_ Ernest w. Goodpaster, M.D., and c. Phillip Miller, M.D. Dr. Joseph Pisani was Executive Secretary. The coa:mittee established a schedule of two-day meetings every two weeks during the months of Septanber, <xtober Section VII, page 4 and N:>ve:nber, in the course of which it would interview senior officials of the r::epartrnent of Health, Education and Welfare and particularly the bureaus of the Public Health Service. The corrmittee planned to devote the first two months to fact-finding, with the last month left for the formulation of the report and recommendations. It proceeded on this basis and completed its report "on time." Dr. Dyer had retired from NIH in 1950, but he obviously retained a lively interest in NIH. When he reviewed the report, he immediately calculated that the conmittee had spent eight days at NIH, six of which were devoted to the review of the $90-million extramural program. The copy of the report in Dr. Dyer's files is peppered.with caustic remarks. In the first place, he was apparently chagrined that despite his being a former Director of NIH, and an available resource, he was never interviewed. A second note was more pointed: obviously the extranely limited time the conmittee spent in reviewing "a complex, important, sound and well established program" was the reason they came up with "such idiotic recomnendations." 75 The reactions of Dr. James Shannon, Dr. Dyer's successor once removed, similarly anphasized "the short time which the conmittee had to consider some very complex problems." 76 Two major objections about the report y;aere entered. One concerned the Long Conmittees' serious reservations as to whether uniformed member·s of the Public Health Service, who originally constituted the largest portion of the intramural scientists at NIH, should not be replaced by a non-uniformed cadre of specially recruited scientists from the universities. Naturally, the pioneers of the program, virtually every one of them out of the PUblic Health Service, bristled with indignation at the suggestion that scientists and doctors trained in circumstances like all ) Section VII, page 5 () others but who took positions in university laboratories rather than govern­ ment ones, were more capable as scientists or administrators. But the recomnendation that drew the strongest and bitterest response from current and former officials of the National Institutes of Health was that calling for "the separation of the extramural program from the National Institutes of Health." It was the opinion of the corrmittee "that the director of NIH, the directors of the various Institutes and their scientific staffs, should devote their whole time and energy to the conduct of the intramural program." The extramural activities - including the teaching grants, fello'NShips and traineeships - said the corrmittee, had ) grown in such magnitude and reach that "the time has come when the responsibility for the program, as well as the study of its immediate and future effects on institutions engaged in medical research and training, J should be placed in the hands of·a separate authority ••• not under the direction of those responsible for the intramural program. 11 77 When he read this recomnendation, the last of seventeen, Dr. Dyer wrote: "Jesus!" How, he wondered, after recognizing "the unique and successful part that the National Institutes of Health have played in support of medical research both within and without the federal goverrnnent," could the conmittee come to that final recarmendation. It was, to him, incredible. Dr. Shannon's official response to the report was sent to the Surgeon General, Dr. Leonard Scheele. The response began "in general agreement with the major objectives held important by the corrmittee," and even in "concurrence with some"of the proposals and the wish to see than adopted as soon as possible." But in the main, Dr. Shannon unloaded a multi-faceted, withering attack on the corrmittee report, ranging from his pointed objection Section VII, page 6 to the corrmittee's comp:>sition and, repeatedly, to the little time it had. The latter problem had naturally prevented its "comprehending fully the evolution and current substance of many programs or grasping the complex realities of the operation of the federal government in general and a large research program in particular." The comnittee simply had not been able to absorb realities such as "the time required to explain to the Executive and Legislative Branches any proposals involving substantial progam change or "the range of factors the head of a major department has taken into account in framing the major organization of this department." The basic problem, Dr. Shannon implied, was "that the comnittee overemphasized the needs of medical schools as the factor which should determine policies governing the operation of the extramural program. 1178 In the end, the Long Commit~ee report got nowhere. The only response it produced, besides the official one by Dr. Shannon to Surgeon General Scheele, was a subsequent request by Secretary Hobby's successor, Marion Folsom, to a task force of consultants headed by former Surgeon General of the Army, General Stanhope Bayne-Jones, to review the Departments' biomedi­ cal research activities; and a similar request by the Senate Appropriations Conmittee to a citizens comnittee headed by Boisfeuillet Jones, Vice President for Medical Affairs at Emory University, to provide a similar assessment for the Congress. Both groups gave the NIH -- its organizational structure, its allocation of funds, and its leadership -- considerable praise.7 9 Thus the treatment given the Long Conmittee report was negative from sources save the one named by Dr. Shannon: the princes of academic medicine, including the heads of some medical schools. Section VII, page 7 In fact, for a full decade after the war, the attitude towards NIH on ) the part of the leading lights of acadanic medicine was an ambivalent one. '11hey were certainly grateful for the ever-growing grants program, and relatively comfortable with it inasmuch as they participated, directly or indirectly, in its direction and its judgments. A number of than obviously doubted that, as the scientific component grew in size and complexity, it could be perfectly managed by uniformed officers of the Public Health Service who, just a few years before, were injecting bismuth into the buttocks of syphilitics. Hence the call for a new professional cadre of scientists/administrators directly out of the ranks of university departments. But the graver reservations were about the intramural program. On the one hand, in the early 1950s the NIH intramural program provided more opportunities for serious, long-term research than any place else. Dr. Donalds. Fredrickson concluded, within a couple of years after he graduated from Harvard Medical School in 1949, that the only way he could become a medical scientist from a financial point of view was to join the "vague but promising new creation rising in Bethesda." His interview in 1951 was with Dr. James Shannon, then Director of Intramural Research at the National Heart Institute," ••• a tall fellow sprawled behind a desk, and barely audible." The result of that interview was that Dr. Fredrickson became one of twelve clinical associates who in 1953 helped to open the Heart Institute's beds of the new NIH clinical center. "This research facility, which placed five hundred beds in close proximity to one thousand laboratories, ·was to be the marvel of its age." 80 Dr. Fredrickson had spent two years, since medical school, at the Section VI I, page 8 Massachusetts General and the Peter Bent Brigham Hospitals, great institu­ D tions which nonetheless "did not prepare me for what I found at Bethesda. There was in this sleepy suburb of Washington a density of talent, freedom of research and intellectual opportunity that may never be equalled." But some of his seniors at Harvard, Mass. General and Peter Bent Brigham thought he was making a great mistake. Dr. Walter Bauer, professor of medicine at the Mass. General, told Fredrickson that he was about to enter "a gigantic federal backwater." Ten years later, Bauer came to the "backwater" himself to recruit the talent which would be the next generation of the medical and basic science faculty at Harvard .81 In fact, Dr. Shannon had gotten a similar reaction in 1950 when he was asked by Dr. Van Slyke to leave the directorship of the Squibb Institute for Medical Research and join NIH to oversee intramural research at the National Heart Institute. A colleague, the aninent physician and teacher Dr • Robert Loeb warned him: "If you go, you' 11 never be heard of again." 82 These stories, and the shifting attitudes, could be replicated a hundred times. VIII In Dr. Dyer's eight-year tenure as Director he had overseen the creation and development of the Division of Research Grants and had helped to establish three new Institutes: the National Heart Institute, the National Institute of Dental Research, and the National Institute of Mental Health. Shortly after he left office, President Truman had signed the Onnibus Medical Research Act of 1950, creating the National Institute of Neurological Diseases and Blindness and paving the way for the creation of those for additional diseases, ~ose dealing with arthritis and diabetes, and with allergies and infectious diseases. In that period, the NIH 83 appropriation had grown from $700,000 to $50 million. For the next five years, NIH was led by Dr. William Henry Sebrell, Jr., another career PUblic Service Officer who had begun his research career under Dr. Joseph Goldberger, the PHS scientist who had proved that ' ) pellagra was due to dietary deficiency and so paved the way for its elimination as a major health problem. Following in the footsteps of his mentor, Dr. Sebrell also became a leading authority on nutrition, making important contributions to the treatment of anemia and cirrhosis of the . 84 · h 1s · d 1r~ · t orsh 1p, · · the conso 1 1· d at1on · 11y 1n · 1 1ver. During NIH was bas1ca mode described previously, with many of the major factors and forces Section VI II , page 2 shaping its growth and its future operating outside its campus. Principal among then -were the development of a strong, bipartisan group of pro-research congressional leaders, who increasingly ignored the hierarchies in the Executive Branch of the government as well as its own, and dealt directly with the leaders of NIH. The third partner in the new trilateral relationship was an assortment of independent citizens, including some biomedical professionals who were also interested in the develoflllent of a dynamic and forceful biomedical research enterprise and in waging war on diseases. This group soon came to be known as the national research lobby. Consolidation of organization and perfection of grant-making systens was accompanied by continuing growth~ 5 By the time of Dr. Sebrell's retirenent in 1955, the NIH budget had gone from approximately $50 million to almost $100 million. That figure, impressive at the time, only a few years later seened like peanuts. For the next decade turned out to be -even more dynamic and expansive than the last, and the National Institutes of Health became the most important biomedical research institution in the world. The triumvirate of forces guiding and governing the national biomedical research enterprise got perhaps its greatest opportunity from the sympathetic successor of Secretary Hobby, Marion Folsom. A man who . _) understood research from his days at the Kodak Corporation, and who, in the eyes of his .Administration colleagues and peers, understood budgets from his days as Under-Secretary of the Treasury in the first Eisenhover .Administration, Folsom believed that the Eisenhover .Administration, like those of Truman and Roosevelt before it, should support the expansion of Section VIII, page 3 the bianedical research effort positively and wholeheartedly, rather than conservatively and apprehensively. In the first year of his tenure, he proposed large increases in the NIH budget to the Bureau of the Budget, an act which confounded the budget director, pleased the NIH director, and opened new vistas of opportunity for friends of NIH in Congress and in the private sector. The sequence of events went like this: In the first few years of the Eisenhower Administration, Congress had regularly added $8 - $15 million to the President's proposed budget for NIH. Folsom, having been assured by a committee of corporate and university research managers appointed by him that NIH was soundly based and soundly operating, proposed a 1957 budget of $100 million. Senator Lister Hill of Alabama, who a year earlier had assumed chairmanship of the Health Appropriations Subcommittee for-the Senate, and Rep. John Fogarty of·Rhode Island who chaired a comparable ccmnittee in the House, simply asked aloud why they should believe that this figure would be adequate for the succeeding year. After all, it was little more than the figure they themselves had proposed for the preceeding year and were told was excessive. The net result was that while Secretary Folsom in persuading his colleagues in the Executive Branch to be more generous to NIH than they earlier had been, he was unable to convince congressional research champions that whatever figure the Administration proposed, it would truly meet important research needs and opportunities. The annual "proof of the pudding" to the Congress was this: As had been the case in 1947 "41en money ran out before all good research proposals could be funded, in 1956 (and all the years in between) study sections had 0 given high ratings for the competence, and the Institutes high ratings for Section VIII, page 4 relevance, of scores of proposed projects for which there were not sufficient funds in the budget. From that point forYBrd, the cost estimate of "approved but unfunded" projects frcm the previous year was the single most persuasive figure of any that the congressional comnittees saw and used, especially including figures in the President's budget. 86 Jim Shannon, who became NIH Director in 1955, shared with his predecessors certain important characteristics. He was a superb researcher, having been awarded the Presidential Medal of Merit for his work on malaria during the Second World War •. He was a part of the NIH family, having earlier chaired the Malaria Study Section and recently served as Associate Director for External Research of the National Heart Institute and Associate Director of NIH. He had an additional credential which his predecessors lacked, that of having been research director of a major pharmaceutical firm. And he had the reputation as being a good manager and a prescient planner, which was a good thing because the greatest growth in NIH history took place during the thirteen years of his tenure. Looking back on that preceding period, it is fair to say that in contrast to the challenges and opportunities facing Dr. Dyer, those of - Shannon's time were less a matter of creating and building, and more that of "riding herd" on a dynamic scientific enterprise which had become so popular and important that the enthusiasm of its friends and supporters sanetimes ran the risk of damaging its scientific substance. Despite periodic problems ananating from the outside, the scientific and administrative leaders of the National Institutes of Health in the ~ 1950s remanber those years with special fondness. The positive political environnent and the enthusiasm of the scientific comnunity were matched internally by a pervasive spirit of collegiality and high morale. Serious Section VIII, page 5 of purpose, those in charge of particular aspects of the enterprise dealt with each other directly, frequently and informally. When a new Institute was created, the newly appointed director would meet with his colleagues and, with a little give and take, they would agree to part with some of their projects which had a little more relevance to the new Institute's focus. Within a new institute, new programs were developed in part by patterning them after established ones. Dr. Knutti remembers that the creation of a training grants program for the National Institute of Arthritis and Metabolic Diseases was accomplished quite easily: I would tell Dr. Doft that I had studied the programs of the other institutes and their training grants programs as examples, and I had come up with a plan for our institute. I would ask him to look it over and if he said, 'O.K., go talk to van,' I would do the same thing with van Slyke [who had moved from the directorship of the Heart Institute to Associate Director of NIH extramural programs in 1962]. Then he'd look it over and say 'Send me a note.' So I would send it to him to him through Daft. 87 In 1956, when an outbreak of scarlet fever and streptococcil disease occured in PUerto Rico, an investigator called Dr. James Watt, then the J Director of the National Heart Institute. The conversation, recalled by Jerry Green, went as follows: It would be great if we could follow those to see how many and in what pattern, will develop rheumatic fever, if at all." Jim was able to say, "What do you think you need to get started on that question." ¼hen he got the information he telephoned several of his council members and in not much longer than 24 hours, he called this investigator back and said, "Go. You are going to get a grant." 88 Even executive secretaries had considerable latitude to take initiative in helping new study sections, or organizing conferences, or proposing new anphases, or suggesting persons who should be invited to serve on study sections and councils. In a word, the spirit of those times Section VI I I , page 6 recognized no rigid institutional, professional or attitudinal boundaries. Further, as Dr. Knutti puts it: There was no petty competition. I don't know of any institute director in my experience that I didn't asstnne liked me; I D liked all the institute directors and I think they all liked each other. They were broad people. Although their opinions might differ -- they might fight like hell about a point - they still respected each other-. 11 89 The camaraderie and collegiality had one more aspect to it that, in the larger political envirornnent, proved to be a trouble spot. As John Sherman sunmarized it: "We liked to say that the NIH operated the grants program for about fifteen years before it realized that it was supposed to have some regulations. That's an oversimplification, but not by much." 90 () IX A conviction increasingly widespread and evennore fervently held was that medical research could eliminate health problems. The corollary conviction was that the biggest enemy of health progress was timidity in providing adequate resources for the war against disease. The budgets leapt up in the first couple of years of Shannon's directorship, slowed slightly at the turn of the decade, and gradually continued to inch up for the remainder of his tenure, surpassing the billion dollar mark in 1965 reaching almost $1.4 billion in 1968, the year he retired. But if growth was the principal characteristic of that period, internal management innovations and external controversy were two others. Fortunately, the basic science support mechanisms put in place by his predecessors stood Dr. Shannon in relatively good stead as he faced myriad positive research and developnent opportunities and several serious political and administrative challenges. Some of the challenges were more than that: at least three of them constituted serious threats. The first was from a subcoomittee of the House Goverrnnent operations conmittee, that on Intergoverrnnental Affairs, chaired by Representative L. H. Fountain of North Carolina. In 1959, the Fountain Committee began an examination of research grants management, to make sure that NIH was meeting its responsibility "for the prudent expenditure of public funds." In 1961, the committee issued its first 0 Section IX, page 2 report finding "that NIH is not adequately organized to administer the grant programs with maximum effectiveness." It offered thirteen reconmendations for improving the grants operations of the Institutes. 91 Dr. Shannon and Surgeon General Luther Terry responded positively, at first, to the Fountain Ccramittee report. Dr.Terry said that he thought, "the study and report rendered a service to the national research effort." Senator Hill and Congressman Fogarty thought the report not very critical of NIH, and so they continued to compete to see which could get his comnittee in his house of Congress to provide the larger increases in the NIH budget. 92 But their congressional colleague proved not to be satisfied with the responsive words. Mr. Fountain quoted approvingly in a newspaper editorial that Fogarty continued to "force-feed the NIH." 93 And he wanted to know in specific terms what Dr. Shannon and his administrative colleagues were going to do to carry out the corrmittee's recomnendations. Fountain had in fact approached the question he posed more as a prosecuting attorney than as a non-partisan analyst of a potential problem. But it did not serve to assuage his concerns -- indeed it excited than -- 'When Dr. Shannon publicly and forcefully reiterated the cardinal rule of NIH grant-making: Selection of good men and good ideas - and the rejection of the inferior -- is the key. All subsequent administrative actions having to do with the adjustment of budgets, and so · forth, are essentia1\Y trivial in relation to this basic selection process. In its June 1962 report, the Fountain Corrmittee responded equally pointedly: The Corcmittee takes strong exception to the view expressed by NIH that all administrative actions subsequent to the selection grant projects are 'essentially trivial' in relation to the basic selection process. The selection process and grant managanent are essential and complementary parts o~fIH research support. Excellence is required of both. Section IX, page 3 '!he impact of that exchange might be summed up in a subsequent congressional appropriation. For the first time in recent memory, Congress approved an appropriation of only $974 million, up only 5% from the preceeding year. The review by a critical conmittee of Congress inspired the appointment, by President Johnson in 1964, of a thirteen-man conmittee 0 headed by Dr. Dean E. Woodridge to begin "a study of how NIH spends its $1 billion budget, to judge whether the American people are getting their money's worth from the expenditure, and to recommend any changes in organization procedure that would in our opinion increase the effectiveness of the program. 1196rn announcing the appointment of the comnittee, the President's message made reference to the fact that NIH was engaged in "direct financial support of 40% of the nation's health research; a pattern of legal arranganents with more than one thousand universities and medical schools, involving more than 17,000 separate grants; growth by a factor of ten in eight years; an annual operating budget approaching the billion dollar level." 97 In the end, the Woolridge Committee reported in February 1965 that "the first and probably most important general conclusion is that the activities of the National Institutes of Health are essentially sound, and that its budget of approximately $1 billion per year is, on the whole, being spent wisely and well in the public interest. 119 ~at was in need of strengthening, said the comnittee, were the organization and procedures of NIH. The latter observation surely pleased the Fountain Conmittee. What pleased Dr.,Shannon was not only the general endorsanent of his management of the enterprise, but the Wooldridge Committee's praise of it for "making a scientifically inappropriate organizational structure an effective arranganent for performing its real mission. 119 9rhis reference was Section IX, page 4 to the increasing tendency of friends of NIH to push a blueprint for growth based on institutes devoted to the conquest of categorical diseases, a tendency which Dr. Shannon resisted with considerable success. Indeed, it might be said that, in his own terms, one of Dr. Shannon's great successes was that in the thirteen years of his directorship only two new institutes were added -- one of than being the National Institute of General Medical Sciences with a specific mandate to support broad, basic research. President Johnson was also reassured, and, in 1966, added $80 million to the NIH budget. Congress added still more and pushed the appropriation, for the first time, over the $1 billion mark. In the same period, another challenge perceived by Dr. Shannon as even more direct a threat occured. This involved that third grant support mechanism, the contract. As its use expanded, beginning in the mid-1950s, so did controversy about it. Its value was essentially two-fold. In the first place, with the extramural grants program being largely propelled in particular directions by Congress and the medical research lobby, and specific research grants being controlled by the scientific establishment outside of NIH, administrators at NIH relied on the contract as a means of filling gaps, and prodding efforts in particular areas. It was also quick and easy to use when needs and objectives were clear: the purchase of 0 equipment or laboratory animals, or consulting services. But it was controversial in the acadanic science corcmunity because, it was thought, sanetimes researchers who had failed to pass the peer review systan subsequently were give~ contracts to do the same research they had proposed in their grant applications. (Dr. Endicott stated flatly on this point that the reverse was sometimes true as well; some of those who failed to Section IX, page 5 pass the merit review process for a contract then submitted grant . . app1 1cat1ons wh.1ch were approved • )lOO Some of the outside lobbyist friends of NIH were pleased that Dr. Shannon and the Institute directors had, in their comnand, the flexible instrument of the contract. And on more than one occasion, a few such friends directly, and indirectly through congressional intermediaries, brought pressure to bear on directors to make particular contracts with particular researchers and institutions. The controversy reached a head in 1963 when, prodded by Dr • Sidney Farber and Mrs. Ma_ry Lasker, chief factotum of the medical research lobby, the National Advisory Cancer Council asked to be able to review proposals for contract work submitted by industrial laboratories. The NIH balked, for there was nothing in the National Cancer Act giving the advisory councils review authority over contracts - merely over grants. On the other side, manbers of the Cancer J Council thought such a right existed in the penumbra of statutory provisions, because their role was, after all, to oversee the whole research effort in the cancer field, especially that supported through extramural devices. Mrs. Lasker and Dr. Farber took the matter up with their friend Senator Hill, and the Senator's report on proposed appropriations for fiscal year 1964 stated: "All monies allocated in this contractual program shall be spent only after review by the National l"lLIVlsory 7\...:J • Cancer Counc1• 1 •.. 101 To Dr. Shannon, this meant that the outside lobbyists were trying to assume control over th!= internal operations of the institutes. He appa­ rently indicated that, if the contract review issue were not resolved, in favor of NIH, he would very possibly submit his resignation. He appealed to HE.W Secretary John Gardner who, once more, worked out what seaned to be a Section IX, page 6 satisfactory approach, the appointment of a comnittee. This one, chaired by Dr. Jack Ruina of the Institute for Eefense Analysis, swiftly reviewed the contract oversight authority claimed by the council. The comnittee supported the Shannon position. The Senate desisted, and another crisis was resolved. 102 But not for long. Mrs. Lasker next took her broader case -- that the NIH was not being sufficiently aggressive in producing results and translating research findings into medical solutions -- to the President. One June 27, 1966, President Johnson invited the NIH Directors, the Surgeon General, and Secretary Gardner to the White House for a discussion of how to get research results more quickly translated into practical answers to disease problens. Ostensibly, the President was enlisting the group as a "strategy council in the war against disease." But his central question - vbether_ "too much energy is being spent on basic research and not enough on translating laboratory findings into tangible benefits for the .American people" -- jarred to the core the assanbled scientists and administrators: 03 Alarm was so great, and apprehensive and negative responses in the scientific conmunity so pervasive,_ that Secretary Gardner invoked a meeting with all NIH consultants, two months after the White House shocker, to clarify the position of the Eepartment. His reassurance was two-fold. First, there was to be no change in the policies supporting fundamental research and, second, that there was not necessarily a "fixed federal health dollar" for which basic and applied research and delivery of services had to compet~. The NIH subsequently produced a report asserting that sixty percent of its monies already went for "applied research" ~nd identifying instances of medical progress resulting from the biomedical Section IX, page 7 research effort over the last two decades. The President, in 1967, helicoptered out to NIH to salute the NIH directorate, staff and grantees, for their "billion dollar success story. •0 4But the political climate had changed greatly and would make every recent and subsequent innovation in grants and contracts, proposed by Dr. Shannon and his colleagues, subject to almost automatic skeptical reception and critical review. As regards other kinds of challenges J;X)sitive possibilities John Sherman recalls two special interests of Dr. Shannon in the early days of his tenure as Director. Both related to his concern about the health of the institutions, as institutions. Research faculties were expanding and, as individuals, receiving increasing federal research monies. Shannon was glad to see this happen and "vigorously defended the imJ;X>rtance of the . 11105 project grant systan as the keystone of the whole extramural enterprise. But at the same time, he was concerned about infrastructure and ••• about help to medicai education. He wanted to find some way that the institutions could exert greater control over their own destiny. So he devised the idea of what he used to refer to as the 'general research and trainin1crrogram,' now called the biomedical research support grant. The idea was that, based on their success in the projects grant systan, institutions could be awarded, on a formula basis, additional money over which deans and other administrators could use to balance off internally its research activities, its teaching and training program, and its overall strategy, which otherwise might be too strongly influenced by the aggregate project awards. The idea was a thoughtful one, and gradually became accepted. But at first, it created, according to Dr. Sherman, "two sets of tensions": One was within the institution, where the faculty frequently described these funds as 'the dean's kitty' with a considerable amount of resentment. They saw it as a draining off of money from the project grant systan. The other was within the NIH, where the institute extramural staffs, 0 Section IX, page 8 including myself at the time, felt that this was a threat to the categorical concept and therefore to the individual institute's categorical programs. 107. A second challenge Shannon took up was that of expanding the nation's overall scientific capability. He was specifically interested in upgrading the group of medical schools and university science graduate programs that were "not quite in the first rank of research-oriented academic institutions" but which, with a modest but continuing infusion of overall . h t we 11 reach the top 1n support, m1g · lOS It was, . a reasonab le per1· od of time. once more, a thoughtful concept and ostensibly within the scope of the NIH charter. But it was also one which, as Dr. Sherman recalls, produced great controversy. There were two problems, one of which was definitional: "This was the first instance in which one couldn't define the process [of selection] clearly; how to set up review criteria for example." The other was, to put it bluntly, the "have" institutions were afraid their institutional support from NIH would be diluted in· favor of some arbitrarily selected "have-nots." Dr. Sherman reme:nbers one reaction typifyng many that occured in the course of a meeting of the national health advisory council by the president of Ohio State University: "He just gave Jim hell because this was 'a bureaucratically dominated, poorly defined program that was giving money H)Q to a favored few!" .After only eleven grants were awarded, the program was discontinued because the criteria for selection - the review mechanisms that operated so well in the project grant arena, accepted and controlled by peers -- could not be developed. Other initiatives~ fared better. Under that broad authority given the Surgeon Ceneral and NIH under the 1944 Act, the Clinical Research Center at NIH had been established in 1953. Later in the decade Section IX, page 9 the NIH went back to Congress to secure, for each of its Institutes, authority to develop "specialized clinical research centers" in medical schools and teaching hospitals around the country, related to the Institute's respective interests. This program simultaneously strengthened the research infrastructure of individual institutions and strengthened the link between research and medicine, a concern of many health science administrators and a preoccupation of all public officials who made public monies available for the great enterprise. Dr. Murray Goldstein, now Director of the National Institute of Neurological Diseases and Comnunicative Disorders was, in those years, working with Frank Yeager at the National Heart Institute. He recalls that only a short time after the developrnent of specialized clinical research centers, basic scientists began to ask for "bonus funds" for their work just as their clinical research colleagues were considered to be getting bonus resources through the clinical centers. The first NIH response, in the context of the still dominant individual project award was: "why would you need it?": So they would say, "if I am going to get an electron microscope, I can't justify it on any individual project. We need a central resource for basic research just as much as you need one for clinical research. 110 It was demonstrably the case that a variety of resources essential to the conduct of basic research were needed, and were needed across a variety of activities, not just for one specific project. This was increasingly true as the technology ,,boom -- in equipment, instrumentation, and chemicals continued. So it seemed appropriate that some support should be awarded in larger blocks to scientists and institutions for their aggregate, Section IX, page 10 inter-related work. The problan was that NIH only had authority to make project grants. But ingenuity and innovation still being very much alive in the collective leadership of NIH, and the purpose being in accordance with one of Dr. Shannon's objectives, in short order the concept and designation "program projects" was decided upon. Once more, the innovation did not come without difficulty. The principal problan lay in deciding who would review and appraise program project proposals. Was it to be the Division of Research Grants through its study sections? Or the Institute and its program officers? The decision was for the latter choice and program projects, with various ups and downs in the interim, continue to the present day. AWq_re that success had brought with it an ever more intense spotlight from the public and the people's elected representatives and their surrogates, Dr. Shannon went to special lengths to minimize the possibility that awards would be made simply because there was money to fund them. At one point he established the rule that of the applications approved by study sections, none in the lower ten percent of the grade scores would be funded. Dr. Goldstein recalls: "It was not an absolute rule, but Jim made it clear that the councils would have to take very special action on an individual basis in order to get funding for a grant in the lower ten 111~ percent." More generally, Shannon retained and occasionally exercised his right and authority not to make grants, even though the council had approved them, if he thought the proposed science was not sufficiently excellent or relevant. After all, the law read that the director of NIH could make awards only with the approval of the advisory councils, not that he had to make all that were approved by the councils. Section IX, page 11 To restrain the natural and, in an earlier time, healthy entrepre­ neurial instincts of NIH managers, Dr. Shannon and Dr. Lindsey instituted a new policy that persons involved in scientific merit review were to be divorced completely from program develoµnent: In the past, it was often true that the executive secretary of an institute review conmittee was also the person responsible for developing the programs and encouraging research in certain fields. In a very authoritarian and purist way, the decision was made at the NIH level [by Dr. Shannon] that it was not appropriate for the same person who was developing the grants to be also reviewing the grants ••• so the study sections became ?~vorced from having program direction implications. 1 overall, Dr. Shannon's management of NIH and the aggregate biomedical research effort was in itself dynamic. As the outside forces treated him, so he treated his colleagues, staff, council members and grantees: pushing and pulling, suggesting and resisting, initiating then restraining. He asked Fred Stone to develop a training program in biophysics and to work with Dr. F.O. Schmidt of MIT in doing so, then watched over their shoulders and offered cautions and corrections at every turn. He persuaded Martin Curnnings to come to NIH from the Veterans Administration, where he was Chief of Medical Research, to start an international program, then became the single most important restraining force on the program's growth. At weekly staff meetings, he so dominated the discussions he had theoretically invited his colleagues into, and so ordered the sequence of argu:nents, that some thought resulting decisions were always made in advance. In retrospect, they attributed the behavior not to egocentricity nor to intellectual arrogance, but to Shannon's broader view and more ordered thought processes. Most of his colleagues later praised him as a good administrator, strong but flexible, with ideas of his own but interested in those of others. But there Section IX, page 12 was no doubt who was in charge. Dr. Jerry Green, director of the Division of Research Grants, remembers that when he first joined the Heart Institute's extramural program, proposals and ideas would be sent up to the NIH "front office" and often no formal answers would come back. Occasionally, the response was simply "No," without reason for it: On a couple of occasions, having worked very hard on the developnent of some kind of proposal, perhaps a new grant program or an increased emphasis in a grant program to be directed at some particular problem, a negative answer would cane back, and I'd ask why. The first couple of times I didn't understand. Then a piece of paper would come back saying, 'S.S.S.' I finally found out that that meant, in house, 'Shannon says so!' That would stop all discussion! If Shannon said so, it was not appealable. 113- X Because of the Fountain Committee and its interrogation and questioning of the administrative basis of decision-making at NIH, all of a sudden a new kind of document was born called "the regulations," where a whole series of "thou shalts" and "thou shalt nots" were written down for the first time as guidelines which had the thrust of law. 114 To put it another way, by the time Jim Shannon stepped down as Director in 1968, NIH had become a bureaucracy. The name and the fact had been successfully resisted for twenty years, but the agency's success and its size finally forced it into an ancient if not necessarily hallowed tradition. NIH had new Institutes and old Institutes with new, expanded, and disease­ directed names. Within the Institutes, categorical programs and program staffs multiplied rapidly. In 1969 for example, the National Heart Institute established five distinct extramural program branches: Arteriosclerotic Disease, Cardiac Disease, Pulmonary Disease, Hypertension and Kidney Diseases, and Thrombosis and Hemmoragic Diseases. In some Institutes, competition among component programs was as keen as it had ever between Institutes. The political and goverrnnental envirornnents in which NIH operated also changed dramatically in 1968, presaging a decade of almost continuous alteration and controversy - and growth. That year, Senator Lister Hill retired from the Senate, thus from the chairmanships of the Labor and Public Welfare Corrmittee, which authorized all legislation pertaining to NIH, and of the Health Appropriations Subcorrmittee, t..he combination of positions that for fourteen years had permitted him to put the public's money where his heart Section x, page 2 was. Representative Fogarty had already gone to his reward. Richard Nixon replaced Lyndon Johnson as President. The decade of the '70s encompassed the terms of six Secretaries of Health, Education and Welfare and five Assistant Secretaries for Health and Scientific Affairs. The latter pattern of turnovers was especially important because, in 1968, a reorganization of the Department's health activities gave NIH the status of an operating agency within the Department, so that the NIH ) director subsequently reported directly to the Assistant Secretary rather than to the Surgeon General. New possibilities for government involvement in the health of the nation had also taken place. Before the Medicare Act of 1965, it was widely thought that just about the only clearly constitutional, hence politically possible role for government in the health field was through research-related grants to individuals and institutions and.grants to states for public health programs, including hospital construction. Now, in the decade of the '70s, Congress authorized a whole spectrum of medical education and health training programs, some for a time under the aegis of NIH and most finally lodging, in the middle of the decade, in the a separate agency dealing with health services and health manpower. The National Research Act of 1974 amended the Public Health Service Act by repealing the NIH's existing research training and fellowship authorities and consolidating limited authorities in the National Research Service Awards office. After that, individual and institutional training grants were restricted to those areas in which there were specifically and conservatively designated as having "shortages." And where training grants were given, research service obligations and payback provisions were to be strictly enforced. Section X, page 3 The decade began with the largest expansion of the government's biomedical research effort since 1946, when Congress and the Nixon .Adminstration teamed up to pass the National Cancer Act in 1971. This made the Cancer Institute a bureau of equal status with NIH, and made possible subsequent annual appropriations in excess of $400 million for cancer research. That act, and the new bureaucratic and hierarchical arrangements, were seen by many within NIH and the medical science corrmunity as pushing categorization of disease problems to a ludicrous extrerne, and force-feeding the already active but necessarily slow scientific effort against cancer, "the dread disease." President Nixon's, Senator Ted Kennedy's, and Mary Lasker's heavy hands drove the new initiative; the Association of American Medical Colleges and Representative Paul Rogers - Senator Kennedy's corrmittee counterpart in the House - ~re the restraining forces. The Nixon-Kennedy­ Lasker combination was an unlikely and, to many, an unholy alliance. 11 S In the same period, the Nixon Adminsitration paid back political friends and Republican fundraisers with government jobs and advisory positions to an I) amazing and in some cases an alanning degree. A senior personnel officer in the Nixon White House said in the early days of the Administration that the ''White House team" considered that there had not been a real Republican President since Herbert Hoover, that the Civil Service and the bureaucracy - were overstuffed with Democrats, and that they intended to clean house and fill the ranks of government officialdom, to the rnaximun, with Republicans. This they proceeded to_do, in the early years, arbitrarily and ruthlessly. Naturally they named "friends," whether or not they had relevant experience and expertise, to the advisory councils of the NIH. Lay manbers of the national advisory councils on biomedical research had, Section X, page 4 in the early years of the grants program, been a matter of concern to many scientists and science managers. But appointed sparingly and selectively, they had gradually proved their worth. Surgeon General J:2onard Scheele caumented in the late '50s: "The enthusiasm of the lay manbers is very hard to keep up with. We medical people are very conservative. These people constantly stimulate us and ranind us of our responsibility.•110The Nixon .Administration took such appointments to extremes, passing then out like gold prizes to entertainers and local political chairmen. The trend reached almost scandalous proportions, and some medical and scientific professionals with traditional credentials began declining to serve. In Dr. Robert Q. Marston, Dr. Shannon's successor, NIH had its first director who had not had long-time NIH experience.In Dr. Robert F. Stone, appointed in 1973, it had its second. Dr. Marston's experience was largely in administration; he had been dean·of the University of Mississippi School of Medicine and director of the new (1966) Regional Medical Programs, temporarily housed at NIH. Dr. Stone was a pathologist with several imp:,rtant research findings to his credit and, like Dr. Marston, a medical school deaJ: 7 As it had been Dr. Shannon's task to ride herd, to keep the procession moving in one direction and protect it from outside forces, it was Dr. Marston's challenge simply to stay in the saddle during a particularly turbulent stretch. Beyond President Nixon's cancer foray, and his Administration's appointments practice, there was the matter of overall budgets. Except for cancer, he was not especially generous. In his budget director, caspar Weinberger, he had a man who set out to prove that he very much deserved the nickname given him when he served as budget director for the state of California: "Cap the Knife." He seened particularly stringent, Section x, page 5 0 on health and education budgets, in marked contrast to his last years in government in the Reagan Administration as Secretary of Defense. In a different decade and a different position, the man who had sliced health boogets became one of the biggest spenders in Cabinet history. Rigid in both instances, his twin rnottos seemed to be "Less is always better for health" and "More is always better for defense." It was Weinberger who first questioned the need for training grants, then rescinded funds Congress had appropriated for them, then essentially removed NIH's broad authority to make them. The budgetary impact on NIH might have been even worse in the mis-'70s, had not Weinberger, when he became Secretary of Health, Education and Welfare in 1973, appointed more knowledgeable and more reasonable men than himself as Assistant Secretaries for Health and Scientific Affairs. So the strong impression at NIH and in the scientific comnunity, in the first several years of the Nixon Administration, was that the President was the enemy of good science and established tradition. What could only be seen in retrospect was that overall the NIH continued to grow. At the end of the Nixon Presidency, with or without the President's specific encouragement or the direct blessing of the President's men, the budget had expanded by roughly $1 billion during his six and a half years in office. If pervasive dependence on regulations is a "negative" characteristic of bureaucracies, the continuing receipt of funds regardless of who the titular leader may be is a positive consequence and a sign of continuing, if not inextinguishable life. An equally felicitous symbol of vibrancy and strength for NIH was the ever-increasing numbers of biomedical scientists supported by the Institutes who received tbbel prizes. Section X, page 6 In 1939 E.O. Lawrence had won the Nobel Prize in thysics; his work had been supported by the National Cancer Institute. It was not until 1950 that the next Nobel Prize winner with an NIH connection was n~ed; he was Philips. Hench, whose work was supported by the Division of Research Grants. In the remaining years of that decade, there were ten additional American Nobel laureates whose relevant work was supported by seven of the Institutes. There were sixteen such awards in the 1960s and twenty-three in the stressful years of the '70s. NIH had clearly become a major element in the international as well as national scientific enterprise and,, in those decades, a driving force in extending the frontiers of science and medicine. In addition to NIH grantees who won the Nobel, four scientists worked in the intramural labs·won such awards between 1968 and 1976. Dr. Marshall N~renberg became the first NIH intramural scientist - and the first U.S. federal employee -- to win a Nobel Prize. 118 Two additional messages were to be found in the growing number and varied sponsorship of Nobel laureates supported by NIH. In the first place, in the early days of the Division of Research Grants, when aside from organizing and administering study sections, it had some funds to "fill in the gaps" left unattended by the categorical programs of the separate Institutes, DRG had invested in ten scientists whose work subsequently won them the Nobel Prize. The National Institute of General Medical Sciences supported forty-two Nobelists from the time of its creation in 1964 to 1987. Further, a number of the twenty-four Nobelists supported by the Cancer Institute and the eighteen supported by the National Heart Institute were given the Prize for their work in what was considered to be more basic than applied areas, thus dramatizing, 0 Section X, page 7 in another way, the link between science and disease conquest and assuring the scientifc comnunity that, despite their focus on particular disease problems, the categorical Institutes of NIH operated under no artificially narrow mandates. A second, underlying, very potent message was that the biological revolution was in full sway. Not only were most of the Nobel awards made for basic breakthroughs in the basic sciences, but such advances opened brand new vistas as to how disease problems should be approached. Dr. Ruth Kirschstein, Director of the National Institute of General Medical Sciences since 1974, asserts that the revolution had an additional critical effect: broadening the scope and requirements of basic science. In her words: What I think is most amazing is that a basic scientist who at one time would have been considered a biochanist or a geneticist or a cell biologist is in fact all of these today. All these fields are blending together now••• So someone who is taking a Ph.D. today in biochanistry will be broadly trained in cellular and molecular biology or .genetics. 119 The biological revolution had another effect, particularly as the possibilities for genetic engineering dawned. It was, in a way, like the dawning of the awful possibilities on those who had helped to create its practical force: an effect of deep concern and apprehension. Very early in that period when the possibilities for good and ill of recombinant DNA technology came to the minds of the scientific conmunity, members of it raised cautions about NIH support of such research. Gradually, at their initiative and under their scrutiny, guidelines for the protection of human subjects, were developed and instituted. Gradually, as well, specific instances qf research telated to genetics proved that practical, positive results far outweighed theoretical negative possibilities. So the 0 biological revolution continued, unhindered by fear. C) Section X, page 8 As the decade moved to a close, a relative sense of calm was restored at the agency and among its constituencies. In 1978, for the first time in a decade since the last collaboration between Dr. Shannon and Secretary Gardner, a Director of NIH had an opportunity to work hand-in-hand with his cabinet officer superior in a positive, forward-looking way. Secretary Joseph A. califano asked Dr. Donald Fredrickson to undertake to develop a multi-year strategy for health research. A national conference was held in Bethesda to draft principles for the federal support of such research, then an HEW steering corrmittee worked out a framework for the future. Dr. 0 Fredrickson chaired both. As he later surrmarized it: The major influence of this activity on HEW and its successor, the Department of Health and Human Services, was manifest in the establishment of a goal of funding a minimun number of new and competing research project grants as the first priority in the setting of the annual NIH budget. The keystone of this "stabilization initiative" was the objective of funding five thousand new and competing grants each years. 12 D Fortunately, the stated objective came to be accepted by both the Executive and legislative Branches and in fact has become a guidepost in the NIH appropriations process from that point to the present. The Administrations of Gerald Ford and Jimmy Carter treated NIH in a more orderly fashion. Inflation took its toll on the upward-moving budgets, so that the agency's higher appropriations did not automatically translate into greater purchasing power. In that same period, medical schools and universities successfully redoubled their efforts to secure a higher rate of indirect costs. The percentage of grants for administration and other in­ direct costs climbed from 20.6% in 1972 to 27.8% in 1979.121This trend made medical school deans and university administrators happy and some scientists Section X, page 9 very unhappy, for they saw it as further eroding the financial support base for actual research. But in contrast to earlier periods, the only strong political pressure in the Carter Administration was for an expansion of the number of wanen, minorities and younger persons to serve on study sections. The fact that Dr. Fredrickson's association with NIH spanned more than two decades befo~e he was appointed director in 1975 was reassuring to the scientific conmunity, as was his capacity for elegant state:nents of scientific position and cogent surrmaries of fiscal need. It was reassuring, as well, that Dr. Fredrickson see:ned to have the support of the new Secretary, at least in the matter of forward planning. But the political dust still had not quite settled when the next Presidential transition occured. () 0 0 D XI 1986 and 1987 were anniversary years for the National Institutes of Health and some of their component parts. The National Library of Medicine chose 1986 as its sesquicentennial anniversary, tracing its origins to a collection of journals and tracts began in the office of the Surgeon () General of the Army in 1836. NIH marked one hundred years of history in 1987, its lineage beginning with a bacteriological laboratory set up by a Public Health Service officer, Dr. Joseph J. Kinyon, at the Marine Hospital on Staten Island in 1887. The Cancer Act and the Cancer Institute were fifty years old in 1987; the National Institute of Mental Health reached age forty in 1986. Additional anniversaries are coming up: the National Heart Institute and the National Dental Institute will "be forty years old in 1988. other dates could "be identified as landmarks in the U.S. Goverrnnent's biomedical research endeavors. The Social Security Act of 1935, in its Title VI, had explicitly authorized the expenditure of up to $2 million for health grants to the states for "investigation of disease" and sanitation 0 problems. The 1944 PUblic Health Service Act gave the NIH the legislative basis for its postwar program, with reanphasized and broader authority to conduct research. But of all the dates and events that could "be signalled out as critically important in the evolutionary expansion of a purposeful, concerted, goverrnnent-supported strategy to defeat disease and enhance health, none surpasses that of the establishment, in 1946, of the Office of Research Grants. 0 0 Section XI, page 2 Dr. Van Slyke was very proud of the fact that, within a year after the NIH grants program was launched by him and his colleagues, 250 aninent American scientists and physicians were involved in advising NIH and, in twenty-one study sections, appraising the scores of grant applications coming in during those early postwar years. He would be astounded to know that, forty years later, more than 2,200 scientists were serving on NIH 0 review groups, including ninety panels of sixty-seven formal study sections of the kind that he and Ernest Allen had set up in the first weeks of their new jobs. van Slyke was by all accounts a visionary man, but he would 0 surely be amazed to know that, in fiscal year 1987, the Division of Research Grants had received 33,804 proposals from scientists and institu­ tions across the country, of which almost 23,000 were reviewed in one or another of the ninety panels of its sixty-seven established study sec- tions. He would be stunned to learn the size and scope of the activity being served by the systen he and his colleages had devised: In 1987, $4.6 billion of the total NIH appropriation of $6.2 billion was invested in almost 28,000 research and training grants in 1,300 institutions around the country. over 90% of those were research grants, including some for . . 122 projects led by 20,000 principal 1nvest1gators. The nature and mix of health challenges and disease threats have changed considerably in forty years. Cancer still looms large in morbidity and mortality figures. Heart and cardiovascular diseases still rank second in their aggregate tol,;J.. Mental Health renains a pervasive and complex challenge made more complex in the 1980s by a persistent and perverse, (5,800 proposals were reviewed by other units of the NIH, and 4,900 by other review groups in the Public Health Service). Section xr, page 3 0 problem of illicit drug use by tens of thousands of Americans, many, though by no means all, in low income groups. In these categories, cancer remained the most frustrating health problem: while progress in detection, treabnent and "cure" -- the latter measured in five-year terms -- improved overall and in some particular categories, the bigger killers such as lung cancer remained dominant over treabnent and over education as to causes; a recent study suggests that approximately 60,000 out of 82,000 of the recent annual deaths from lung cancer are specifically attributable to smoking! 23While breast cancer treatment now produces survival rates of 75%, its incidence continues to go up. The Heart Institute and NIH proudly point to a 43% reduction in the death rate from coronary heart disease since 1972, a staggering figure, attributable to both medical and surgical advances and lifestyle changes, including nutrition and exercise·habits, also encouraged by recent research . . 12 4The National f indings. . . Institute . 1 and Corrmun1cat1ve of Neuro 1ogica . . Disorders and Stroke had reason to be gratified by an equally impressive figure: death rates from stroke were down more than 48% in the same fifteen-year period~ 25with respect to those disease problems identified by Dr. Parran in the 1940s as major national health problems, one had clearly 0 been brought under control, if not totally vanquished. Based principally on research on and trials with fluoridation by the National Dental Institute in its early years, dental caries had been reduced dramatically, particularly in younger generations, to the point that closing of dental schools became, in the 1980s, a conmen phenanenon. As always, new health threats arose, the most dramatic one being the frightening spectre of AIDS (Acquired Irrmune Deficiency Syndrome). Not G Section XI, page 4 identified as a specific disease until 1979, exact patterns of transmission were not understood for several more years, yet by 1982 it was clearly an urgent problem. In 1981, the Center for Disease Control had reported 200 cases and 177 deaths - a death rate of 88%. Within six years, by the third quarter of 1987, some 42,000 cases had been identified and almost . death.126The first half of those had resulted in . . ed wit cases were associat . h sexual conduct of homosexual males; the deadly virus was isolated in blood. Later cases included some caused by contaminated blood used in transfusions; others stemned from rare but dramatic instances of laboratory accidents. There were some wanen victims and a few newborn infants were afflicted. As the population sample of those affected diversified, public alarm increased. Even as the nation and the _federal government attempted to organize themselves, in typical disjointed and uneven ways, some actions and accomplishments were encouraging. By 1987, NIH was spending half a billion dollars per year on AIDS research, much of it in-house, and most of it targeted. A number of medical advances, almost all supported by NIH -­ particularly the National Cancer Institute and the National Institute of Allergies and Infectious Diseases - were already occuring. The drug AZT_ was proven to retard the spread of the disease in 90% of the patients to whan it was given. Other chemicals were rapidly being tested and tentative vaccines were being readied for clinical trials in the United States and Canada. This progress.was heartening, even suprising, given the recency of the identification of the disease. It helped greatly that the National Cancer Institute had for more than a decade, in the laboratory headed by Dr. Robert Gallo, been working Section XI, page 5 on the viral theory of cancer. Dr. Gallo was thus able to identify a connection, first conceptually and then in laboratory experiments, between the slow viruses thought to produce certain kinds of cancers and HTLV-III, the virus carrying AIDS. It added up to another dramatic example of the serendipity of scientific exploration. The most problematic areas seem to lie not on the research front, but on those of public education and statistical projection. The Public Health Service published figures projecting an expanded base of infection -- 1.5 million persons in 1987 -- which yielded dramatic numbers of possible AIDS cases five years into the future: a cumulative total of 270,000 cases and 179,000 deaths by the end of 1991) 27 If these figures hold up, an estimated 50,000 persons will die of AIDS in that year, a figure remini­ scent of, but somehow more frightening than, 40,000 deaths from tuberculosis fifty years earlier. One thing that gave pause to a long-time observer of such predictions were similar extrapolations within the last fifteen years from other statisticians in the Center for Disease Control regarding swine flu and Iegionaires' disease. At the root of the statistical and educational problem was a behavioral one. sexual practices in the homosexual comm.mi ty changed rapidly from the point of the elucidation of the disease pattern. But intravenous drug use among a growing population of addicts did not change. A high proportion of the new AIDS cases identified in 1987 ~re among poor blacks and Hispanics, and a high percentage of those cases correlated with drug addiction and the use of contaminated needles. Hence a new concern was that if new delineations of the portions of the populations likely to be affected narro\\ed it to those outside the mainstream -- gays, Blacks, Section XI, page 6 Hispanics and intravenous drug users -- the effort to combat AIDS might slacken. Meanwhile, small wars against other disease problems also continue to go forward. The 30,000 Americans afflicted with cystic fibrosis took heart from the recent identification of the chromosome that carries the deadly gene, background work for which was sponsored by the National Cancer Institute and the Cystic Fibrosis Foundation. The 35 million Americans who suffer from allergies were encouraged by the identification of the antibody responsible for their allergic reactions, research supported by the Allergy and Infectious Diseases Institute. Further progress was reported against diabetes, gout, and even baldness. vhile no significant advances were made against another terrifying disease, Alz.eheimer's, the increasing number of older Americans could at least take heart that, in work sponsored by the National Institute on Aging, it had been proved demonstrably that Alz.eheimer's was not simply a by-product of aging, but a specific disease with specific elements toward which new scientific research could be applied .128 Treatment of diabetes became more sensitive, and effective when research supported by the National Institute of Diabetes and Digestive and Kidney Disorders distinguished between two types of the disease. For the first time in medical history, an effective drug treatment for gout was developed based on research on metabolic defects supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. (Less progress being made against arthritis prompted the separation of components of NIAMS and the creation in 1986 of a separate National Arthritis Institute.) 129 Section XI, page 7 As for the political and budgetary context of the 1980s, NIH probably benefited from President Reagan's concern about U.S.-Soviet rivalry in arms and technology and the technology-based economic challenge of friendly countries. The President therefore looked favorably on "R and D". Of all domestic programs, one of few not seriously affected in the first Reagan term's efforts to cut domestic expenditures was NIH. In fact, the agency had acquired such a reputation that the conservative Heritage Foundation, which had contributed analyses and individuals to the Reagan election and re­ election campaigns, identified NIH as virtually the only domestic agency of goverrnnent whose work was so important, so efficiently carried out, and of such high benefit-to-cost ratio, that no cuts should be made in it. Nonetheless, just as shock waves in the stock market continue to reverberate in the psyches of investors, even after specific crises pass, so the perception of another period of negative political influences and declining budgets accompanied the election and even the re-election of President Reagan. Dr. James Wyngarden who succeeded Dr. Fredrickson as NIH Director in 1982, found that one of his greatest challenges was reassuring the biomedical science conmunity, institution by institution and in some cases department by department and association by association, that'research funds were not drying up, indeed were more than keeping up with inflation and almost with highly rated applications. Within five years after he assumed the NIH directorship, the agency's budget climbed from $3.7 billion to more than $7 billion. In another repetition of history, Dr. W'yngaarden and his colleagues also found thanselves defending the peer review systan against political challenges from the outside, in this instance, the Chairman of the Senate Ai;propriations Ccmnittee, Senator Mark Hatfield of Oregon. Troubled Section XI, page 8 because the universities in his state received comparatively little biomedical research funds, the Senator asked the General Accounting Office to review the patterns of health and science research funding and the role of peer review systans of NIH and NSF in making such awards. The ~O reports may not have assuaged Sen. Hatfield's concerns, but it did show that peer review was not the reason that biomedical and other science research funds went to particular regions, states, institutions or scien­ tists}30 Instead, it documented the existence of strong, vibrant health science research capacities in every region of the country, particularly in one hundred institutions that spanned the length and breadth of the land, even if it clustered strongly in the Northeast and on the West coast. Nor was. this group precisely the same hundred that had been the top recipients of comparable kinds of research funds twenty years earlier. Instead, the picture anerging from the statistics and the charts of the ~O showed two definite trends that must make the pioneers of the grants programs smile with special satisfaction: first is the steady buildup of particular scientific capacities, built around individuals and departments in every part of the country. Second is the developnent of new kinds of scientific strengths, in new areas or newly clustered groups of established scientific disciplines, combining to show the dynamism of scientific interchange and the anergence of new individual and institutional leaders.13 1. C.J. van Slyke, Ernest Allen, :Ralph Meader and their colleagues may or may not have had in-mind building geographically dispersed constituencies as one reason for their concerted efforts to assure that NIH took geography into some account. But their early attention to this factor, and their successors' further manifestations of concern about it, Section XI, page 9 had, in effect, resulted in a strong practical shield against political influence on the expert review process. Indeed, the only successful assaults on peer review were those that went around it, rather than against it. For example, when the Democratic Majority Leader of the Senate, Sen. Robert Byrd found himself unable to persuade Dr. Wyngaarden and his NIH colleagues that they should somehow ignore study section and advisory council jtrlgments about support of cancer research and treatment in his state of West Virginia, he caused to be inserted in an authori~tion and appropriation bill a specific line itan for the developnent of such a center in the budget of the Secretary of Health and Human Services, not that of NIH. In this continuously dynamic climate, Dr. Wyngaarden urged the reversal of a research support t~end of the past two decades, an increasing "central direction" of the focus and scope of scientific initiative. Particularly when the big bulge in the Cancer budget occured in the early '70s, and with the assignment of a large fraction of the new funds to the contract mechanism, NIH began to see the balance of its research support changed in favor of initiatives coming from inside rather than outside, from central direction rather than individual investigators. In fact, says Dr. Wyngarden, ":We fell under 45% of our total budget in investigator- 132 initiated research project grants." In the five years of his tenure to date, that trend has been reversed, and now approximately 63% of the extramural budget of NIH goes in support of investigator-initiated research, about 10% higher than was the case in 1982. Dr. Van Slyke would be pleased with another developnent as well. In the last several years, NIH has cut back on the length of applications and at Section XI, page 10 least in that way, simplified the application and the review processes. The interchanges between scientists in the field and administrators at NIH is not nearly as informal and personal as it was in the old days, but there are new ways for would-be researchers to secure helpful information. One is the requirement of the Freedom of Information Act that researchers be allowed to see "pink sheets," those sunroaries of the study sections' appraisals of their proposals prepared by the executive secretaries. To be able to understand exactly what manbers of the study sections thought -were the strengths and -weaknesses of a proposal is to enable a stronger application in a subsequent round. And even though the numbers of actual review panels increased to approximately ninety, the cost of processing a research or training grant has come down in real dollars, dropping from 133 around $1,800 in 1972 to approximately $1,100 in 1987. Thus new systems and procedures, from computers to sunshine laws, have helped the NIH reinvigorate an old spirit, that of open communication and efficiency. Similarly, new discoveries have helped in the reassertion of an old conviction. Dr. Michael Zasloff of the National Institute of Child Health and Human D=velopnent, has worked for some years on biological elements in reproduction, using the African clawed frog in his experiments. This basic research led him to the observation that the frogs never got infections from "surgical procedures," and subsequently to the identification of elements in the frog's skin which constituted the protection. The exciting possibility is that artificially replicated ''magainin" can become a new medical weapon against'a wide spectrum of infectious agents in humans. Comnenting on his discovery, Dr. Zasloff gave poW=rful reaffirmation of the theme sounded forty years before by Dr. Dyer and Dr. van Slyke: "You never () Section XI , page 11 know the ways of research. Let science be free ••• We are not so smart as to know if what we do today is going to be important tomorrow. 11 Or, he might have added, if so, how. Dr. Zasloff's work had its counterpart in doz.ens of other examples. Dr. Ruth Kirschstein points out an equally unusual and beneficial one: work supported by the Institute of General Medical Sciences on recombinant DNA technology has led to the ability genetically to engineer bacteria to clear up oil spills, or on a smaller but wider scale, to dissolve hair stuck in plumbing systans. F.quilibrium may never be maintained for long. But those which the NIH must maintain sean to be in good shape on the fortieth anniversary of the grants program and the hundredth year of the institution itself. The intramural program continues to produce first-rate results and share first-rate people with the scientific world. The extramural program ranains by far the largest component. Yet it has been relieved of one important burden: where project research and program research grants once dominated the budgets of many medical schools, they now no longer bear that central burden; reimbursements for patient care are now the larger source of income, though a continuingly troubling one. With another government push to reduce overhead costs, and with appropriated.dollars continuing on a definite though not dramatic upward climb, funds for research, within those hundreds of institutions where it is performed, are a stable elanent and relatively secure corrmibnent. The NIH today is a large agency, encompassing twelve institutes, a Section XI, page 12 clinical center and five other divisions - including the Division of Research Grants. The National Library of Medicine, one of those divisions, houses the world's largest repository of medical literature, including information on recent scientific and medical advances, immediately accessible by computer to physicians throughout the nation and much of the world. The NIH staff of more than 14,000 persons includes more than 3,183 scientists and physicians, most of whom work at the 300-acre Bethesda campus. For the hundreds of scientists and scores of lay persons who serve on its review comnittees, such service is considered a professional honor, as well as a professional or civic obligation. Continuous organizational changes that have occured at NIH through the years include: the addition of new institutes and divisions; the reformulation of their names and :the alteration of their specific responsibilities; responsibility for overseeing trial regional medical programs and other medical technology delivery systems; the lodging and dislodging of particular programs (i.e., National Institute of Mental Health, Bureau of Health Manpo~r Fducation) within its scope of activities. These have occurred in the context of changing political alliances and · shifting sands of executive and congressional politics. Yet none of these factors or forces, together or separately, has, in the end, seriously affected the central mission or the guiding principles. The enterprise is alive and well and, to an amazing extent, functioning along lines envisioned and hoped for by the NIH pioneers. The grants program can still boast of its bill of rights for scientists - freedom of inquiry, freedom of initiation. The administrators are still keeping all the balance wheels aligned. Section XI, page 13 Surely one reason for the continuity in the orderly pursuit of scientific progress and medical accomplishment, despite the enormity of change, is related to the continuity of the personal connection. Jim Wyngaarden came to NIH in 1953 where he worked in the Laboratory of Chemical Pharmacology at the National Heart Institute when Jim Watt was Director. Dr. Fredrickson was an NHI colleage. Subsequently, Dr. Wyngaarden was a clinical associate at the National Institute of Arthritis and Metabolic Diseases when Jim Shannon was Director of NIH and Van Slyke was Deputy Director. Indeed many of the current senior NIH figures knew and worked with some of the pioneers. Dr. Jerome Green, for example, had a thirty year association with the National Heart Institute before becoming Director of the Office of Research Grants for NIH in 1986. The circle of leaders and potential leaders has grown greatly; the networks begun by Van Slyke, Allen and company have multiplied exponentially. But the institution and its scientific principles are touchstones for virtually every biomedical scientist in the country, and many beyond our shores. Despite the vastness of its reach and the formalization of its bureaucratic systems, it remains a human place, almost a familial enterprise, with strong personal links between the past and the present. Those that lead it and work there today share firmly with their predecessors a devotion to science, a concern for the human health, and an optimistic spirit. NOTES (Section I) 1. Annual Report of the Surgeon General u.s. Public Health Service, Fiscal Year 1936, p. 2. 2. Id., p. 11. 3. Interview with Dr. Kenneth Endicott, March 16, 1986. Transcript (National Library of Medicine, History of Medicine Division) p. 4. 4. The overall PHS budget figures are taken directly from "'Ihe Budget of the U.S. Government, 1938." The NIH and ~I figures, including the amounts for grants, ~re taken from the 1986 NIH Almanac, inasmuch as these figures have been reordered, by function, beginning in FY 1938, to provide a consistent base for all subsequent years. · 5. These landmark dates and statutory authorities have been recorded in a variety of places. I have relied primarily on two: Marian Qakleaf, History of the Extramural Programs, 1930-1960, unpublished manuscript, National Library of Medicine, History of Medicine Division; and the 1986 NIH Almanac, U.S. Deparbnent of Health and Human Services, NIH publication No. 865, Sept. 1986, pp. 4-5, 10-11. 6. Interview with Dr. Martin Cunmings, May 15, 1986. Transcript (National Library of Medicine, History of Medicine Division) p. 2. 7. Interview with Dr. Endicott, Transcript, op. cit., p. 3. 8. Interview with Dr. J.R. Heller, March 26, 1986. Transcript (National Library of Medicine, History of Medicine Division) p. 3. 9. Interview with Dr. Endicott, Transcript, op. cit., p. 3. 10. Ibid. (Section II) 11. The surrmary recitation of the work of the OSRD_ and its Canmittee on Medical Research is taken largely from my book, Politics, Science and Dread Disease: A Short History of U.S. Medical Research Policy (Cambridge., Mass: Harvard U11versity Press, 1972) Chapter II, pp. 15-31. Se also Irwin Stewart, Organizing Scientific Research for War (Boston: Little, Brown Co., 1948). 12. Chester s. Keefer, "Dr. Richards as Chairman of the Comnittee on Medical Research," Annals of Internal Medicine, Vol. 71, No. 5, pt. 2, November 1969. 13. Ibid. CJ 14. Annual Report of the Federal Security Agency, 1947, Section III, "PUblic Health Service," p. 263. 15. Ibid. 16. Strickland, op. cit., pp. 16-17. 17. Interview with Dr. Stone, April 7, 1986. Transcript (National Library of Medicine, History of Medicine Division) p. 9. 18. See sumnary of legislation in the 1986 NIH Almanac, op. cit. p. 11. 19. Vannevar Bush, Science: The Endless Frontier (Washington: Office of Scientific Research and ~velofn}ent, 1945; reprinted, National Science Foundation, July 1960). 20. Dr. Daniel Fox, Professor of History of Science and Humanities at State University of New York, Stony Brook, is one who has traced carefully the bureaucratic tensions and interagency rivalries of this period. Some of his conclusions were presented in a lecture at the School of PUblic Health, The Johns Hopkins University, March 19, 1986. 21. Donald C. swain, "The Rise of a Research Empire," Science, December 14, 1962. (Section III) 22. Interview with Dr. Ernest Allen, 1986. Transcript (NLM, History of Medicine Division) pp. 1-2. 23. Three perspectives on what transpired have been provided by the three principals. See my interview interview with Dr. J. Roderick Heller, March 26, 1986. Transcript (NLM, History of Medicine Division) p. 9; transcript of oral interview with Dr. van Slyke by Harlan Phillips, 1963 (NLM, History of Medicine Division), pp. 21-22; and transcript of oral interview with Dr. Dyer by Harlan Phillips, Novanber 13, 1963, (NLM, History of Medicine Division), p. 3. 24. van Slyke - Phillips interview, op. cit., p. 22. 25. Daniel Fox lecture, op. cit. 26. Annual Report of the Federal Security Agency, "Public Health Service," 1946, op. cit., p. 236. 27. Transcript of oral interview with Dr. Allen by Harlan Phillips, April 3, 1963 (NLM, History of Medicine Division) P. 4. See also Ora Marashino, comp. "National cancer Institute Historical Materials," National Cancer Institute, History Division, Bethesda, Ma. 28. Transcript of Allen - Phillips interview, op. cit., p. 10. 29. Ibid. 30. Annual Report of the Federal Security Agency, 1946, "Public Health Service," p. 231. 31. C.J. van Slyke, "New Horizons in Medical Research," Science, Vol. 104, No. 2711, December 13, 1946. 32. Annual Report of the Federal Security Agency, 1946, "PUblic Health Service," op. cit. 33. Endicott - Strickland interview, op. cit. p. 6. 34. Transcript of oral interview iwth Dr. Dyer by Harlan Ehillips, November 13, 1963 (NLM, History of Medicine Division) p. 3. (Section IV) 35. van Slyke, "New Horizons," op. cit. p. 561. 36. van Slyke - Phillips interview, op. cit. p. 39. 37. Interview with Dr. Price, May 2, 1986. Transcript (NLM, History of Medicine Division) p. 3. 38. "The Division of Research Grants of the National Institutes of Health: Its History, Organization and Functions, 1945-1962," (Washington, D.C.: U.S.D:partment of Health, F.ducation and Welfare, Public Health Service, 1963) Pub. No. 1032. 39. Van Slyke, "New Horizons", op. cit. p. 561. 40. Id • p. 563. 41. Id. p. 559. 42. Transcript of Dyer - Phillips interview, op. cit. p. 2. 43. Transcript of oral interview with Dr. Felix by Harlan Phillips, February 8, 1963 (NLM, History of Medicine Division) p. 41. 44. Interview with Dr. Price, op. cit. p. 2 45. Ralph G. Meader, o. Malcolm Ray and Ixmald T. Chalkey, "The Research Grants Branch of the National cancer Institute," Journal of the National cancer Institute, Vol. 19, No. 2, August 1957, pp. 228-229. 46. Interview with Dr. Stone, op. cit. p. 2. (Section V) 47. Interview with Dr. Yeager, August 8, 1986. Transcript (NLM, History of Medicine Division) p. 5. J 48. Interview with Dr. Stone, op. cit. p. 7. 49. R.G. Meader and W.W. Payne, "Cancer Research Facilities Construction Grants," Public Health Reports, Vol. 66, No. 24, June 15, 1951, p. 3. 50. Id. p. 5. 51. Irving Gerring, "U.S. Public Health Service Grants," Journal of the American Water Works Association, Vol. 47, No. 11, Novanber 1955, p. 1075. 52. Id. p. 1098. 53. Ernest Allen, "Why are Research Grants Disapproved?" Science, Vol. 132, Novanber 25, 1960. 54. Interview with Morris Graff and Irving Gerring, July 1986. Transcript (NLM, History of Medicine Division) p. 10. 55. Interview with Dr. Fuhr, July 1986. 56. Interview with Dr. Stone, op. cit. p. 9. 57. Transcript of oral interview with Dr. Allen by Harlan Phillips, April 3, 1963 (NLM, History of Medicine Division) p. 35. 58. Interview with Dr. Stone, op. cit. pp. 5-6. 59. Ibid. 60. Interview with Dr. Green, July 29, 1986. Transcript (NLM, History of Medicine Division) pp. 6-7. 61. Meader and Payne, op. cit. p. 2. 62. Id. p. 3. 63. Id. p. 2. 64. Interview with Dr. Knutti, May 16, 1986. Transcript (NLM, History of Medicine Division) p. 11. 65. Interview with Dr. Endicott, op. cit. pp. 10-11. 66. Ibid. 67. Interview with Dr. CUmmings, op. cit. p. 13. 68. Ibid. 69. Transcript of oral interview with Dr. Felix by Harlan Phillips, February 3, 1963 (NLM, History of Medicine Division) p. 41. (Section VII) 70. Strickland, Politics, Science and Dread Disease, op. cit. p. 85. 71. Van Slyke - Phillips interview, op. cit. p. 35. 72. Id., p. 36. 73. "Medical Research Activities of the Department of Health, Fducation and Welfare," Report of the Special Conmittee on Medical Research of the National Science Foundation, Decanber 1955, Appendix, pp. 67-68. 74. Id • , p. 69 • 75. Rolla E. Dyer Papers, National Library of Medicine, History of Medicine Division, "Long Cormnittee Report." 76. Manorandum to the Surgeon General, PHS, from the Director, NIH, December 12, 1955, Rolla E. Dyer Papers, op. cit. 77. "Medical Research Activities of the Department of Health, Fducation and Welfare," (Long Committee Report) op. cit., pp. 40-41. 78. Manorandum to the Surgeon General, PHS, from the Director, NIH, op. cit. 79. Strickland, Politics, Science and Dread Disease, op. cit., pp. 159-162. 80. Interview with Dr. Fredrickson, O:tober 10, 1986. Transcript (Nqvi, History of Medicine Division) p. 2. 81. Ibid. 82. Recalled by Dr. Donald Lindberg, Director, National Library of Medicine, in conversation on O:tober 20, 1987. (Section VIII) 83. See 1986 NIH Almanac, op. cit., p. 20-21, 137. 84. Id. p. 21. 85. See Strickland, Politics, Science and Dread Disease, op. cit., Chapter III passim. 86. Id. Chapter IV passim. 87. Interview with Dr. Knutti, op. cit. p. 5. 88. Interview with Dr. Green, July 29, 1986. Transcript (NLM, History of Medicine Division) p. 5. 89. Interview with Dr. Knutti, op. cit. p. 7. 90. Interview with Dr. Sherman, September 5, 1986. Transcript (NLM, History of Medicine Division) p. 3. (Section IX) 91. Strickland, Politics, Science and Dread Disease, op. cit., pp. 171-172. 92. Id., pp. 172-173. 93. Id., pp. 172. 94. Id., pp. 174. 95. Id., pp. 176-177. 96. Id., p. 178. 97. Ibid. 98. Ibid. 99. Id., p. 178-179. 100. Interview with Dr. Endicott, op. cit. 101. Strickland, Politics, .science and Dread Disease, op. cit., p. 205. 102. Id., pp. 205-206. 103. Id., pp. 207-208. 104. Id., p. 209. 105. Interview with Dr. Sherman, op. cit., p. 6. 106. Ibid. 107. Ibid. 108. Id. p. 7. · 109. Ibid. 110. Interview with Dr. Goldstein, June 3, 1986. Transcript (NLM, History of Medicine Division) ., p. 15 • 111. Id. p. 9. 112. Id. p. 8. 113. Interview with Dr. Green, op. cit. p. 8. (Section X) 114. Interview with Dr. Goldstein, op. cit., p. 9. 115. Strickland, Politics, Science and Dread Disease, op. cit., Chapter XII passim. 116. Id., p. 136. 117. 1986 NIH Almanac, op. cit., pp. 21-22. 118. Id., pp. 166-167. 119. Interview with Dr. Kirschstein, April 30, 1986. Transcript (NLM, History of Medicine Division) p. 3. 120. Interview with Dr. Fredrickson, op. cit., "Bibliography," p. 4. 121. "Statistical r:ata - Research Grants: Percentage of Indirect Costs to Total Grant Dollars Awarded." Department of Health and Human Services, NIH, Office of Associate Director for Administration, February 22, 1985. (Section XI) 122. Basic figures from A Century of Science for Health: National Institutes of Health, NIH Office of Communications, 1987. Updated figures through October 1987 provided by Division of Research Grants, NIH. 123. Susan Okie, "Smoking's Contributions to U.S. Deaths", Washington Post, October 30, 1987, p. A23. 124. "Research Accomplishments", A Century of Science for Health, op. cit. 125. Ibid. 126. The figures on AIDS used here are from several imnediate sources, including interviews and newpaper articles, but all are based on figures published by the Center for Disease Control, U.S. Public Health Service, 1987. 127. Dan Colban, "AIDS: The Growing Impact." Washington Post Weekly Health Journal, June 2, 1987, pp. 10-11. 128. "Research Accomplj.shments," A Century of Science for Health, op. cit. 129. Ibid. 130. "University Funding: Information on the Role of Peer Review at NSF and NIH" (Washington, D.c.: General Accounting Office, March 1987) • 131. "University Funding: Patterns of Distribution of Federal Research Funds to universities" (Washington, D.C.: General Accounting Office, February 1987). 0 132. Interview with Dr. Wyngaarden, August 13, 1987. Transcript (NLM, History of Medicine Division) p. 6. 133. Id., p. 1. 134. Quoted in Peter Caws, "Nature: Preserve it for Science," Washington Post, August 10, 1987, op. ed. page. C)