Disciplinary Contours

The transformation of the life sciences in America in the twentieth century was shaped by earlier developments. Several areas of the biological sciences experienced significant growth during the second half of the nineteenth century. Museums of natural history, notably the Museum of Comparative Zoology in Boston, the Smithsonian Institution, Yale's Peabody Museum, and the American Museum of Natural History in New York City, fostered research and educational programs in botany, zoology, and paleontology. Marine biological laboratories, especially the one at Woods Hole, had grown by the beginning of the twentieth century into thriving scientific communities, where embryology and cytology flourished. The nation's agricultural research stations and agricultural colleges became active sites of applied and pure research in plant and animal breeding; attention to practical problems at coastal and lake fisheries contributed to the growth of embryology, ecology, and population biology. Diverse researches on animal nutrition and husbandry, plant and animal pathology, microbiology, and soil sciences developed during the late nineteenth century (albeit at different rates), under the auspices of the United States Department of Agriculture.1.

The closing decades of the nineteenth century also saw the nascence of experimental biology, a biology curriculum based in liberal arts colleges and graduate schools, and independent from medical education. The champions of experimental biology, among them Thomas H. Morgan (at Bryn Mawr and Columbia), Edmund B. Wilson* (Columbia), Charles O. Whitman, Frank R. Lillie** and Jacques Loeb** (University of Chicago), H. Newell Martin (Johns Hopkins), and after 1920, William J. Crozier (Harvard), sought to break away from the intellectual traditions of natural history, descriptive zoology, botany, and vertebrate morphology. Imbued with the German research ideal, these American biologists, focusing on cytology and embryology, emphasized experimental evidence as a basis for explanations of life phenomena. The research laboratory became central to the scientific ethos of experimental biology.2.

Ironically, the integration of experimental biology into the academic curriculum was catalyzed through the medical connection, which biologists had sought to diminish. Motivated to a large extent by the reform of the medical curriculum, leading American universities had begun promoting in the late nineteenth century a core biological curriculum that included experimental embryology, cytology, and physiology, with the intention of upgrading medical training through fundamental biological knowledge. The commitment to scientific medicine also encouraged the development of physiological chemistry, the precursor of biochemistry. Although at the turn of the century departments of biology were still dominated by the older traditions of descriptive zoology and botany, new disciplinary trends had begun to emerge, and an institutional infrastructure-biology departments, professional societies, and journals--had been fairly well established.3.

While some aspects which came to characterize the organization of biological knowledge in modern America were already in place early in this century, several distinctive features of the modern life sciences evolved in the following decades. The twentieth century, as several manuscript sources in this bibliography document, was shaped by its own political forces, social trends, and intellectual currents, resulting in the creation of uniquely American institutions of science which encouraged the development of new disciplines and research programs.

One of the new disciplines which emerged in the United States in the early decades of the twentieth century and is well documented in the APS collections was general physiology. In contrast to the old medically oriented physiology which focused primarily on structure and on specific tissues and organs, the new physiology emphasized quantitative explanations and fundamental mechanisms. It also stressed generality -- the unity of biological phenomena in all organisms from protozoa to humans. As such, general physiology was partly a continuation of the split from the older descriptive morphological tradition, and in part a move away from clinical medicine.

The convoluted path of general physiology reflected uncertainty of disciplinary direction. In perennial struggle against colonization by medicine, general physiology represented more of a reaction than an active plan; by overlapping with biochemistry and biophysics, general physiology was vaguely defined, and did not have a coherent agenda. Non-medical general physiology was promoted by some of the champions of experimental biology, among them J. Loeb**, F.R. Lillie**, W. J. V. Osterhout*, and Simon Flexner*; aspects of their scientific activities are documented in the manuscript sources at the APS.4.

Perhaps the greatest influence of all was exerted by Simon Flexner*, who had made his mark in bacteriology and pathology before the turn of the century; the extensive collection of his papers at the APS provides a wealth of information on his scientific contributions. As director of the Rockefeller Institute for over thirty years, he was responsible for bringing in Loeb**, Osterhout*, Levene**, Northrop**, Wendell M. Stanley**, Thomas M. Rivers*, Peyton Rous*, Donald D. Van Slyke**, and Ralph W.G. Wyckoff**.. As chief editor of the Journal of Experimental Medicine, as trustee of major foundations that promoted the life sciences, and in his advisory role for numerous organizations, Flexner played a pivotal role in shaping experimental biology, general physiology, biophysics, and biochemistry in America.5.

Given the variegated nature of general physiology (and the broadness of experimental biology), the visions of various practitioners gave rise to different research programs. Lillie's** work, for example, centered primarily on the physiology of fertilization, utilizing immunological and biochemical concepts of biological specificity. At the same time, as the manuscript sources show, he exercised strong influence on the development of experimental biology and general physiology through his departmental leadership at the University of Chicago, and through his powerful administrative contacts and wide-ranging scientific networks.6.

The German émigré Jacques Loeb**, on the other hand, shunned administrative entanglements; his impact on general physiology was made primarily through his research and his charismatic personality. An arch-determinist, Loeb**, unlike Lillie**, approached physiology as a purely mechanistic process, completely reducible to the laws of physics and chemistry, and his investigations on fertilization and phototropism were aimed at the control of life. Like Lillie**, he promoted the idea that general physiology would best advance the life sciences when free from its role of servant to medicine.7.

Loeb's** ideas were closely shared by his protégé Osterhout*. Trained in a botanical tradition, Osterhout* utilized plant cells to study general vital phenomena such as membrane permeability, chemical composition and electrolytic balance in cell fluids -- highly quantitative studies which encompassed plant physiology, biochemistry, and biophysics. Beyond the laboratory, Osterhout* exerted influence on the growth of general physiology through his involvement and long-time co-editorship of the Journal of General Physiology, through publications aimed at a wide readership, and his leadership positions in professional societies.8.

In contrast to the mechanistic reductive approach of Loeb** and his disciples (who also included John H. Northrop** of the Rockefeller Institute), the research school of W. B. Cannon* at Harvard's Laboratory of Experimental Physiology fostered an integrated approach to vital processes. His classic neurophysiological studies on the sympathetic nervous system, along with related studies of endocrine function, led him to coin the term "homeostasis" to describe a self-regulating process by which the constancy of the internal environment is maintained. Although Cannon's* correspondence at the APS does not deal with his research, it does document his influence within the scientific establishment and his impact on experimental biology.9.

Relative to experimental biology and general physiology, biochemistry (or physiological and biological chemistry, as it was called until the 1930s) was a late bloomer in the United States. Biochemistry (like physiology) received its greatest impetus within a medical context, and depended on the support of physiologists. Biochemistry, however, quickly surpassed physiology in status and resources. At the end of the nineteenth century only three departments -- Russell H. Chittenden's** at Yale, Victor C. Vaughan's at the University of Michigan Medical School, and John J. Abel's at Johns Hopkins Medical School -- offered research opportunities and courses in biochemistry. By 1910, the majority of medical schools had founded biochemistry programs and departments, and biochemists had established a disciplinary identity within professional societies and through the Journal of Biological Chemistry. By the 1920s, biochemistry was generally recognized as a discipline of primary importance and commanded abundant resources.10.

The founders of American biochemistry were trained in Germany, where this subject was quite advanced during the second half of the nineteenth century. Their embryonic research programs tended to resemble those of their German mentors. Focusing mainly on basic composition of substances in plants and animals-carbohydrates, proteins, enzymes -- American biochemists emphasized blood chemistry, and chemical analyses of products involved in such metabolic processes as digestion and respiration. These early biochemical programs were influenced by the strong traditions of nutrition and agricultural chemistry in American universities. For example, at Yale, the work at the Connecticut Agricultural Experimental Station greatly influenced the development of protein chemistry under R. H. Chittenden**; his memoirs at the APS recount these early developments.

At the turn of the century, the impact of medical reform which swept through American universities not only accelerated the growth of biochemistry, but also inclined it toward a clinical service role. Until about 1940, biochemistry, except at those universities where the connection to agriculture and nutrition remained dominant (notably at the University of Wisconsin, where hundreds of biochemists were trained in food and drug research), developed principally in medical schools and was informed by concerns of physicians and medical physiologists. But even in the medical context, biochemistry underwent changes in the 1920s and 1930s, forging closer institutional ties and intellectual alliances with organic chemistry and physical chemistry. Increasingly, biochemists received their training in departments of chemistry, which were undergoing rapid growth after World War I. They applied new theories and laboratory techniques to study not only problems directly relevant to medicine, but also questions in theoretical biochemistry such as reaction kinetics, oxidation-reduction, and chemical structure.

As the papers of the influential biochemist William Mansfield Clark* show, from the 1920s to the mid-1950s he led at Johns Hopkins Medical School an elite research group that emphasized studies of equilibria and oxidation-reduction reactions in metabolic systems. Similarly, the growing influence of chemistry on biochemistry resulted in the appointment in 1928 of Hans T. Clarke* as head of the biochemistry department at Columbia's College of Physicians and Surgeons. His department, which focused on organic chemistry, and especially on the chemistry of proteins and steroids, became by 1940 one of the largest and most influential in biochemistry in America.11.

Several research currents, notably enzymology and protein chemistry, shaped the direction of American biochemistry. During the 1920s and 1930s theories of enzyme kinetics were developed and hundreds of enzymes which catalyze diverse vital reactions were discovered, culminating in the early 1930s with the crystallization of several proteolytic enzymes. Manuscript sources at the APS on Nobel laureate John Howard Northrop**, who led these researches at the Rockefeller Institute, include several files on his scientific activities.

The 1930s also saw the growing influence of the German organic chemist Emil Fischer on the development of protein chemistry in America. As his numerous students became directors of their own research programs, they emphasized Fischer's peptide theory of protein structure. Protein chemistry assumed a principal place within biochemistry, and the Rockefeller Institute, which had traditionally stressed a physico-chemical approach to biological knowledge, was in the vanguard of this field. In fact, this trend was in part responsible for the eclipse of nucleic acid research in the 1930s, since the primacy of proteins was regarded as the explanation to all phenomena involving biological specificity.12.

The manuscript sources on Phoebus A. T. Levene** and Max Bergmann* of the Rockefeller Institute contain materials on these trends in biochemistry. The Bergmann Papers* also document trends in leather chemistry, and through his extensive correspondence with biochemist Karl P. Link** of the University of Wisconsin, also developments in agricultural chemistry.

By the mid-1940s, due to the impact of gene research and the rise of molecular biology, the attention of biochemists was increasingly drawn to the biochemistry of nucleoproteins and nucleic acids, culminating in 1953 in the elucidation of the double helical structure of DNA, the genetic blue-print of life. This discovery, in turn, accelerated the shift away from protein research toward the biochemistry of nucleic acids. But in the 1930s and 1940s, only a few researchers were attracted to the study of the biological properties of nucleic acids. Geneticist Jack Schultz* at the California Institute of Technology was one of the early believers in the role of nucleic acids as hereditary determinants.

Schultz's* extensive correspondence with his close friend, Swedish biochemist Torbjorn O. Caspersson**, affords rare insights into the intellectual and social dynamics within the community of biochemists whose research interests were dominated by the protein paradigm. Similarly the papers of biochemist Erwin Chargaff* (in H. T. Clarke's* biochemistry department at Columbia), who had worked out in the 1940s a key element in the DNA puzzle, are an invaluable source on the intellectual and social challenges inherent in scientific work which is outside the mainstream of research.13.

The differentiation between physiology and biochemistry has not resulted in a total intellectual separation between these disciplines. There has been a wide common ground between the two areas, which in turn has accommodated within it other overlapping fields, specifically microbiology, immunology, and pathology. The close relations between physiology, pathology, and microbiology (especially bacteriology) developed during the late nineteenth century. With the acceptance of Pasteur's germ theory of disease and the rise of bacteriology, physiological processes in animals and plants could no longer be fully explained apart from microbiology-bacteriological knowledge then consisting mainly of microscopical classifications of bacteria based on morphology, differential staining, and life cycles. Following the medical reforms at the turn of the century, bacteriologists (trained mainly in Germany) had become central to the growth of life sciences. The discovery that sub-microscopic filterable organisms called viruses cause diseases in plants and animals gave rise in the 1910s and 1920s to the new specialty of virology. Initially subsumed under bacteriology or microbiology, the study of viruses evolved by the 1940s into a major research area within molecular biology and cancer research.14.

The papers of Simon Flexner* include extensive material on American microbiology in general, as well as on Flexner's* own contributions to the study of bacteria and viruses. The Library also houses the papers of microbiologists Peyton Rous*, Peter K. Olitsky*, and Thomas M. Rivers* of the Rockefeller Institute, scientists who had pioneered physiological investigations of animal and plant viruses. Rivers* and Rous* were especially instrumental in promoting virology through leadership of their respective departments, their key positions in professional societies and scientific journals, and their wide collegial networks.

In addition to its ties to the physiological and medical traditions, microbiology was also shaped by chemistry. In contrast to physiologists and microbiologists like Rous*, Olitsky*, and Rivers*, biochemists usually viewed bacteria as a bag of chemicals-especially enzymes -- to be extracted, purified, characterized, and manipulated.15 For example, biochemist Florence Seibert* spent her long career at the University of Pennsylvania (Phipps Institute) studying the chemical properties of the active principle in tubercle bacilli. As her papers illustrate, although she worked on clinical problems in a quasi-medical institution, she maintained strong intellectual and social bonds to the chemists' establishment that had shaped her career.

The scientific activities of Seibert*, as well as those of Rivers*, Rous*, and Olitsky*, also show that it is difficult to separate neatly the growth of microbiology (especially in the medical context) from the science of immunology. Indeed, with the acceptance of the germ theory of disease, the two fields had developed side by side; investigations of diseases of microbial origins paralleled studies of immunity. Serum therapies in the late nineteenth century gave way to searches for antibody-producing vaccines and therapeutic drugs of the twentieth century. Pharmaceutical research formed an important research area where microbiology, biochemistry, physiology, and immunology intersected intellectually, institutionally, and commercially.

As with the branched development of microbiology, immunology differentiated into cellular (or humoral) and chemical subspecialties. The cellular approach, exemplified by the research of Rous*, Rivers*, and Olitsky*, emphasized the role of immune cells (e.g., leucocytes, phagocytes, and macrophages) that defend the body against foreign invaders (antigens). Advocates of the physico-chemical approach to immunology, on the other hand, stressed the specificity of chemical reactions by which antibodies neutralize the effects of antigens, a research area known as immunochemistry or molecular immunology. Among the founders of immunochemistry were the Swedish Nobel laureate Svante Arrhenius**, and Austrian-born Karl Landsteiner* (discoverer of the four blood groups and their immunogenetic significance) of the Rockefeller Institute. While the Library's manuscript sources on these scientists do not deal directly with immunochemistry, they do offer interesting insights that help place each scientist's work within the social context which shaped his Weltanschauung.16.

Biophysics, though a strong intellectual and technological force in the life sciences, was not only a late bloomer but also an anomalous field. The salient features of institutional infrastructure which serve as indicators of disciplinary growth -- scientific societies, journals, departments, endowed chairs -- have been largely absent in American biophysics. While in the second decade of the century there were influential research programs in biophysics in England (e.g., those of A. V. Hill and E. D. Adrian) and in Germany, biophysics research in America was just emerging.

Probably one of the barriers to the coalescence of biophysics as a discipline was its great diversity. A catch-all term for technical and theoretical applications of physics to biology, biophysics since the late nineteenth century encompassed investigations in muscle physiology, electrophysiology, acoustics, pneumatics, respiration, blood-flow, and cardio-vascular function. Biophysics utilized principles of optics and the laws of light propagation in microscopy, photosynthesis, and in studies of color vision. During the first two decades of the century, biophysics also came to include aspects of quantum theory and the interaction of radiation with biological matter: applications of x-rays and ultraviolet rays to organisms and cells, radiation genetics, methods of x-ray diffraction for probing biomolecular structure, spectroscopy, the use of radioisotope tracers, and beginning in the 1950s, the techniques of nuclear magnetic resonance. With a primary emphasis on techniques and instruments and with specialized literature on a wide range of topics scattered in diverse scientific journals, biophysics remained an eclectic field that did not mature into a bona fide discipline until well into the 1950s.

In the 1920s, American biophysicists had begun carving out a small niche for themselves in the interstices between physics, engineering, biology, biochemistry, and physiology. Some of these early investigations (notably at the Universities of Michigan, Chicago, Wisconsin, Rochester, Pennsylvania, Columbia University, the Carnegie Institution of Washington, and the Rockefelier Institute) had begun to outline the scientific content of biophysics, initiating an awareness of its potential disciplinary autonomy. A new subdivision, formally designated as biophysics, first opened at the Rockefeller Institute in 1927 under Ralph W.G. Wyckoff**, who worked on the biological applications of x-ray crystallography and later on the design and construction of the ultracentrifuge. Although the division was terminated upon his departure in the late 1930s (and revived in the 1950s under the Institute's new director Detlev W. Bronk), Wyckoffs** embryonic research program, as the manuscript sources on Wyckoff** reveal, was very important for the growth of biophysics.17.

It seems that by the late 1920s biophysics was "in the air," so to speak. In 1928 the new biology division at the California Institute of Technology under T. H. Morgan established a department of biophysics, and Hugo Fricke at the Biological Laboratory at Cold Spring Harbor founded a special laboratory of biophysics. That same year, the biophysics institute -- the Eldridge Reeves Johnson Foundation -- was founded at the University of Pennsylvania under the leadership of Detlev W. Bronk, the dean of American biophysics. A center for a wide range of studies in neurobiology and biophysics, the Johnson Foundation served as a nursery of the new field. Although the manuscript sources on Bronk are not substantial, minor correspondence with Bronk appears in many of the collections in this bibliography. Furthermore, the English biophysicist F. J. W. Roughton* -- a specialist on hemoglobin and oxygen transport in the blood -- had participated in projects at the Johnson Foundation. His correspondence and extensive scientific records document various aspects of biophysics not only at the University of Pennsylvania but in other institutions as we11.18.

These diverse activities did not coalesce into a discipline, however. As late as 1938 Warren Weaver, director of the Natural Sciences Division of the Rockefeller Foundation, observed that "biophysics... is still for the most part an orphan subject. Able young physicists, however genuine their interest, hesitate to devote themselves to a profession which is insufficiently recognized to offer a reasonable chance for a permanent job."19.

The anomalous development of biophysics may well serve as a corrective to arguments of institutional determinism in the history of science. In spite of its lagging disciplinary status, biophysics had a major impact on the transformation of biology into a sophisticated technology-based science; these trends are reflected in a number of manuscript sources. Osterhout's* studies of membrane permeability and electrophysiology may be properly included in biophysics. In addition to the material on Ralph W.G. Wyckoff** and on F. J. W. Roughton*, the papers of Mildred Cohn* of the University of Pennsylvania contain accounts of various investigations in biophysics, especially the early applications of nuclear magnetic resonance to biological problems. The Roughton Papers* and the Cohn Papers* are enhanced by the material on Britton Chance**. The papers of Alexander Hollaender* (one of the founders of radiation genetics) provide a rich record on the growth of radiation genetics after World War II, and on the relation of that field to regulatory issues of environmental safety.

Patronage, Politics, and the Rise of Research

The intellectual developments in physiology, biochemistry, and biophysics (and related fields) were shaped by complex social factors, and influenced by national and global politics. These interrelated social and political forces shifted patterns of patronage of the life sciences, stimulated the rise of new research institutions (including industrial research laboratories), and especially through the two world wars led to a reorganization of scientific research and to an influx of émigré scientists to the United States. These trends in American science are represented in most of the manuscript sources in this bibliography.

The pattern of scientific patronage during the first five decades of this century may be roughly described as cyclical, having shifted from the public to the private sphere and back again. Early in the century, the life sciences -- heavily weighted toward practical goals, especially agriculture -- were supported mainly by the government. A wide range of biological investigations were conducted in the bureaus of the United States Department of Agriculture and in agricultural colleges. Some of these institutions (such as the University of Missouri and the University of Wisconsin) eventually became leading research centers in the life sciences; the manuscript sources on W. J. Robbins*, K.P. Link**, W. J. V. Osterhout*, W. M. Clark*, and P. K. Olitsky* document aspects of these developments. Agriculturally oriented science continued to be predominantly government science even in the following decades.

The state and federal governments also supported practically oriented research programs related to public health; the papers of E. L. Severinghaus* reflect aspects of these activities. But as the files in the Flexner Papers* on Wickliffe Rose and the Rockefeller Sanitary Commission show, public health causes, medically oriented projects, and bio-medical education were active domains of the large philanthropies, notably the various Rockefeller boards. With the creation of the Carnegie Corporation in 1911 and the Rockefeller Foundation in 1913, the support of the life sciences (with the exception of agriculture) increasingly came from the private sphere.20.

Initially, before the 1920s, the Rockefeller and Carnegie foundations supported little research by individuals in universities. Having come into existence during the Progressive Era, the large foundations reflected the spirit of reform that permeated the first and second decades of this century. These reforms, manifested in major changes in public education, in the rise of various social movements, and in large-scale civic projects, were inspired in part by the growing influence of business, industry, and technology in American life, and were informed by a drive for efficiency and technical training. Science, previously occupying only a marginal place in American education, increasingly moved from the periphery to the center of the school curriculum.

Biology played an integral role in that transformation. Viewed as a means for effecting changes in society, the life sciences (and by extension the behavioral sciences) became the underpinnings of several social programs which received generous support from the large foundations. The support for eugenics and genetics research by the Carnegie philanthropies and Rockefeller's Bureau of Social Hygiene are examples par excellence of social reforms of the Progressive Era which were based on applied knowledge in the life sciences.21 The APS library is a prime repository of archival sources on eugenics; however, being an aspect of genetics, they are outside the scope of this bibliographic guide.

The emphasis by the Carnegie and Rockefeller foundations on large scale projects of social utility did not preclude their supporting basic research (though not in a university context). During the first decade of the century, two major research institutes which had an enormous impact on the growth of the life sciences were established: the Carnegie Institution of Washington (1902) and the Rockefeller Institute for Medical Research (1901). Within the broad spectrum of its research activities (which included the physical, earth, and planetary sciences), the Carnegie Institution gave considerable support to biological research at its laboratories: the Department of Plant Biology (the Desert Laboratory), the Department of Marine Biology, the Nutrition Laboratory, the Department of Embryology, and the Department of Genetics (Station of Experimental Evolution) at Cold Spring Harbor.22 The papers of Warren Harmon Lewis*, who worked at the Carnegie Institution, afford insights into activities at the Department of Embryology, and both the desert and marine laboratories.

Cold Spring Harbor* was enormously important for the growth of genetics, and Milislav Demerec*, its director after 1940, made it into a mecca for molecular biologists. It evolved into an international scientific center that promoted the cooperation of physicists, chemists, and biologists on fundamental problems in biology, biochemistry, and biophysics, with an emphasis on gene research. The papers of Milislav Demerec* and Jack Schultz*, as well as the Cold Spring Harbor* collection, document aspects of this transition from classical genetics to molecular biology.

In contrast to the Carnegie Institution of Washington, the Rockefeller Institute supported strictly biomedical research; clinical studies were conducted in the adjacent Institute Hospital. America's principal leaders of scientific medicine, the Johns Hopkins bacteriologist William H. Welch and his disciples ("Welch rabbits"), were a major force in planning the institute; the policies were implemented by Welch's protégé, Simon Flexner*, the Institute's director for over thirty years. Motivated by the gospel of scientific medicine, Flexner* and the Institute's leaders emphasized a physico-chemical approach to fundamental problems in physiology. While the German research ethos inspired individual freedom of inquiry, the Institute also encouraged interdisciplinary team research. In fact, the Rockefeller Institute became Adolph von Harnack's model of privately supported, project oriented science when he founded the Kaiser-Wilhelm Institute in 1913.23.

Beginning in 1906 with three departments -- Pathology and Bacteriology, Physioiogy and Pharmacology, and Chemistry -- the Institute by the 1930s had expanded into four laboratory buildings. Even in the Institute's Hospital, approximately half of the space was designed primarily for laboratories, reflecting the primacy of research. The Institute's laboratories created in the 1920s included physical chemistry, photobiology, biophysics, cytology, and endocrinology. The Institute's Princeton branch -- the Department of Animal and Plant pathology -- became by the late 1930s a world-class center of biochemistry and microbiology, where J. H. Northrop** and W. M. Stanley** conducted their Nobel Prize-winning work on proteins.24.

Aside from the emphasis on theoretical physico-chemical aspects of vital phenomena, the Rockefeller Institute was in the vanguard of laboratory technology. The Institute's workshops produced some of the most sophisticated instruments in the United States, including x-ray spectrographs, electrophoresis apparatus, and ultracentrifuges; some of the important innovations in chemical separation techniques of chromatography in the 1940s took place at the Institute. These various laboratory technologies became indispensable to the study of cells and molecules, and placed the Institute in the forefront of biomedical research. By the mid-1950s, the Rockefeller Institute (renamed The Rockefeller University) had become not only an international training center, but also a model for other departments and institutions in the life sciences.25.

The manuscript sources at the Library are especially informative regard this remarkably influential research institute. The voluminous collection of Simon Flexner's* papers, which documents the scientific and administrative activities at the Institute, is complemented by manuscript sources on biochemists, physiologists, microbiologists, and biophysicists Taken together, the sources on Peyton Rous*, T. M. Rivers*, W.�J.�V. Osterhout*, Max Bergmann** K. Landsteiner*, P.�K. Olitsky*, R. W.�G. Wyckoff**, P.�A. T. Levene**, J. H. Northrop**, J� Loeb**, and W. M. Stanley** (and the papers at the APS of Florence R Sabin, James B. Murphy, Eugene L. Opie, George W. Corner, and Rufus Cole) provide scholars with materials which cover a substantial portion of the history of the Rockefeller Institute.

The manuscript sources at the Library illuminate another important chapter in the history of the life sciences: the involvement of the United States in World War I, and the effect of the war on the subsequent direction of American science. On the technological and scientific level, cooperative war projects gave rise to new instruments and devices, to novel materials, methods, and treatments. These developments, in turn, transformed the character of warfare and made science indispensable to it. On the social level, war activities were responsible for the emergence of a scientific community self-conscious of its importance to national welfare. World War I, sometimes referred to as the "chemists' war", was particularly important in the emergence of a strong academic and industrial chemistry. Led by a powerful scientific establishment, in which Simon Flexner* played an important role, America's men of science played up the lessons of the war. Emphasizing the benefits of cooperative research and the need for new scientific institutions, they lobbied for a substantial increase in financial support for science from the private sector, especially the Carnegie and Rockefeller foundations.26.

Historians of science have focused their attention on cooperative war projects which involved the physical sciences and engineering: submarine detection devices, aeronautic instrumentation, wireless communication, methods for computing projectile trajectories, atmospheric research, and projects of the Chemical Warfare Service. Relatively little, however, has been written on war-related projects in the life sciences. The Rockefeller Institute, for example, played an important role in these activities. Under the leadership of Simon Flexner* -- Lieutenant Colonel and consultant on Army medical problems during the war -- the chief task of the Institute was to conduct courses in bacteriology, clinical chemistry, and pathology for medical officers and technicians. Hundreds of army personnel were trained by the institute's staff, among them Olitsky* and Rous*. In addition to war-related medical training, Flexner's* laboratory developed a rapid method for producing serum to combat an outbreak of cerebrospinai meningitis, an antidysentery serum, and new techniques for typing and treating pneumonia. P. A. T. Levene's** laboratory was converted into a production site for pharmaceuticals such as barbitols and antidotes to mustard gas; in Loeb's** division J. H. Northrop** developed a microbial process for the production of acetone for explosives. Rous*, together with two colleagues at the Institute, developed methods for preserving human blood in blood banks, which facilitated blood transfusions.27.

The manuscript sources on Flexner*, Olitsky*, and Rous* contain material on some of these war projects, affording glimpses into the early links between the life sciences and the military, ties which served as a precedent for the mobilization of life scientists during World War II. Complementing these sources on actual projects are the correspondence files between Osterhout* and Arrhenius** and between J. T. Lloyd and Robbins*, which contain detailed accounts of Europe during the war years, the effects of the war on the international scientific community, and changing attitudes toward German science. These sources indicate that the involvement of the life scientists in the war was of greater significance than previously acknowledged.

As a result of the rising status of science during the war and the promotion of basic research as a national resource, science began to be supported on a massive scale by the large foundations. Beginning in 1919, the National Research Council -- an institution established during the war introduced a program of postdoctoral fellowships financed by the Rockefeller Foundation. During the 1920s, under the aegis of various boards, the Rockefeller philanthropies funneled millions of dollars into fellowship programs and awarded multi-million dollar grants to science departments in universities. During the 1920s, the Rockefeller's General Education Board and International Education Board emphasized fundamental research in the physical sciences: physics, mathematics, and chemistry. Departments in the life sciences did receive grants-in-aid and young researchers were awarded Rockefeller Fellowships in biological fields, but these fields were not the first priorities.28.

As the Seibert Papers* show, the Guggenheim Foundation was an important source of funding for talented individuals in the life sciences.

Beginning in the 1930s, with the consolidation of the Rockfeller philanthropies, the Rockefeller Foundation reformulated its science policy, concentrating its resources on the biological sciences. Under the directorship of the former University of Wisconsin mathematical physicist Warren Weaver, the Rockefeller Foundation's Natural Sciences Division allocated millions of dollars to grants and fellowships specifically aimed at developing a biology based on applications of physics and chemistry to fundamental problems of life. By circumventing institutional barriers and by crossing boundaries of traditional disciplines, Rockefeller grants and fellowships promoted cooperative projects which merged genetics, biochemistry, physiology, biophysics, microbiology, and immunology into the hybrid discipline of molecular biology.29.

In order to accomplish this massive reorganization of the life sciences, Weaver and his staff depended on the advice of experts -- leaders in those branches of the life sciences relevant to the new program. Flexner*, of course, had a great deal of input into the "new biology" (about which he had several reservations), as did F.R. Lillie** and W.B. Cannon*. As the manuscript sources show, these men who had shaped the course of experimental biology at the turn of the century also influenced the design of the new biology in the 1930s. The papers of W.J. Robbins* are a highly informative source on the activities of the Rockefeller Foundation during its organizational phase of the early 1930s. Having traveled extensively in Europe and Asia, Robbins prepared detailed reports for the Foundation, describing numerous laboratories he had visited. These reports are not only a valuable source of information on the life sciences abroad, but also offer insights into the modus operandi of the Rockefeller Foundation during the 1930s. Bergmann's* correspondence with the Rockefeller Foundation illuminates the purposes and policy of its fellowship program.

The 1920s and 1930s also saw the rise of cooperation between the pharmaceutical industries and the universities. Sobered by the lessons of the war (particularly the dependence on German drugs), and with the abrogation of German-owned patents in 1917, American drug companies came to regard biochemical research as an essential resource for the maintenance of a competitive edge, both in wartime and peacetime. Several pharmaceutical houses in the 1920s courted researchers in physiology, biochemistry, pharmacology, and microbiology; they established consultantships and industrial fellowships, and cultivated joint projects with university departments. Particularly strong links among academic biochemistry, pharmacology, and nutrition developed in the 1920s between the University of Wisconsin and a number of food and drug industries; Elmer L. Severinghaus* played an active role in that liaison.30.

Due partly to industry's growing emphasis on research, and partly to the war's lessons, America's custodians of "pure Wissenschaft", who previously had looked askance at utilitarian science, entered increasingly into industrial research. A new breed of life scientists emerged, among them A. N. Richards of the University of Pennsylvania and Merck & Company, Roger Adams of the University of Illinois and Abbot Laboratories, A. L. Tatum of the University of Wisconsin and Parke-Davis, all of whom forged early links between academic life sciences and pharmaceutical houses. Eli Lilly and Co., for example, began its cooperative relations with academia by sponsoring a few projects in Woods Hole in the 1920s; by the 1940s it had developed in-house research facilities as well as an elaborate system of contracts with biochemists and physiologists. Some of the collaborations of Lilly (and other pharmaceutical companies) are documented in the Seibert Papers*, the Chargaff Papers* and the Neuberg Papers*. Hoffmann-La Roche, having established sophisticated in-house research in the 1930s, was able to attract Severinghaus* to become its director of research in the 1940s. Several letters in the Severinghaus Papers* afford interesting insights into issues concerning industry-university relations in the life sciences.

The Impact of World War II

The life sciences in the 1930s were also greatly influenced by the political events in Europe, forces that culminated in the eruption of World War II. With the rise of the Nazi Party in Germany and the growing virulence of anti-Semitism, the academic futures of Jewish scientists in Germany became bleak. Prominent researchers at universities and the Kaiser-Wilhelm Institutes were relieved of their posts, and the careers of young scientists of Jewish descent were truncated. Many deposed scholars from the physical, biological, and social sciences made their way to America. With the support of the Rockefeller Foundation, and through special funds and committees established to help refugee scholars, these European scientists found academic posts and research opportunities in the United States.31.

The intellectual migration of the 1930s had important consequences for the development of the life sciences, especially biochemistry and molecular biology in the 1940s and 1950s. Austrian biochemist Erwin Chargaff*, who developed his program under H. T. Clarke* at Columbia, made some of the most significant contributions to nucleic acids research in the late 1940s, work which led to the elucidation of the structure of DNA. A vociferous critic of American culture, Chargaff* maintained strong professional and emotional bonds with European colleagues; his correspondence offers cross-cultural perspectives on the intellectual and institutional aspects of biochemistry research. In contrast to Chargaff*, Max Bergmann* adopted his new homeland with great enthusiasm. His research program in protein chemistry at the Rockefeller Institute was extremely influential, and as his correspondence reveals, he helped several German biochemists to emigrate to America. Among these deposed scholars was Carl Neuberg*, former director of the Kaiser-Wilhelm Institute for Biochemistry, and a leader in carbohydrate chemistry. The Neuberg Papers* contain extensive correspondence with prominent scientists in Germany, documenting a sadder and less successful story of an intellectual migration.

The political events of the 1930s that precipitated the exodus of German scientists eventually drew America into the war in 1941. During the "preparedness" phase (1940-1941), the leaders of American science reorganized the nation's scientific resources for the demands of war. The Office of Scientific Research and Development (OSRD) was established under the leadership of Vannevar Bush, Director of the Carnegie Institution of Washington, for the purpose of contracting with educational institutions, scientific organizations, individuals, and industries in order to coordinate war-related research. Within the OSRD, the Committee on Medical Research (CMR) was assembled under the leadership of the University of Pennsylvania pharmacologist Alfred N. Richards to develop war projects in the life sciences.32.

The organization of divisions and projects during World War II was far more orderly and efficient than during World War I. A subcommittee on medicine dealt with problems such as infectious and tropical diseases and aviation medicine. The papers of F. J. W. Roughton*, an expert on blood oxygen and high-altitude physiology, document some of his war activities in the United States. In addition to CMR projects, work related to diseases was conducted within the Army's and Navy's Medical Corps. A team of researchers at the Rockefeller Institute -- the "Naval Research Unit" under the direction of (Captain) T. M. Rivers*, worked on projects such as epidemic diseases, bacterial and viral research, immunology, and typing of pneumonia; the Rivers Papers* contain several files about these war-time projects.33.

Research in physiology within the OSRD included the development of blood substitutes and agents for boosting resistance to disease. The blood fractionation project at Edwin J. Cohn's** biochemistry laboratory at Harvard (described in the Joseph Stokes, Jr. Papers at the APS) was a principal achievement of CMR. Most biochemists worked on the production of hormones, penicillin, drugs, and bio-organic war chemicals, projects which were frequently coordinated with pharmaceutical firms. In fact, an important by-product of the war effort was an even closer tie between the drug industries and academic research in the life sciences. The Chargaff Papers* contain several files on biochemistry work within the OSRD, as well as on the subsequent ties of his research to the food and drug industries.

At the end of World War II (which, in spite of the life scientists' contributions, is sometimes referred to as the "physicists' war") science emerged even more triumphant than in the previous war. Massive war research such as the Manhattan Project, the development of the proximity fuse, and the penicillin and blood-fractionation projects forged strong links between science and government, bonds that could not be readily severed. Scientists learned what could be accomplished with the large-scale combinations of basic research and rapid development of its applied technologies. The OSRD was disbanded in 1945, but leaders of American science played up the "lessons of the bomb" and lobbied for the support of "big science" by the federal government. Not everyone embraced the wartime model during peacetime. The proponents of free enterprise, especially the Rockefeller and Carnegie foundations, opposed the concept of "planned" research. After a few years of public debate over the patronage of science, the convoluted path to federally supported science culminated in 1950 with the creation of the National Science Foundation.34.

Although the life sciences within the OSRD were not as visible in the war effort as some of the large-scale projects in the physical sciences, researchers in the biological sciences were quite conscious of their contributions, as well as of their relative lack of recognition and prestige. They launched a vigorous campaign to secure for themselves a stable institutional position within the new federally funded science. The founding of the American Institute of Biological Sciences (ATBS) in 1947, and the substantial expansion of the National Institutes of Health (NIH) were the outcomes of these efforts. Little has been written about the AIBS, which by the mid-1960s experienced serious problems with its finances and reputation; the AIBS files in the papers of W. H. Lewis*, P. Rous*, and J. Schultz* help illuminate this little-known episode in the history of the life sciences. The papers of plant physiologist W. J. Robbins*, a central figure in the coordination of postwar science, are a rich source on the strengthening of biology in the postwar era.35.

The National Institutes of Health, which supported the researches of several scientists included in this bibliography, has remained the single most important federal institution in the life sciences, in terms of policy-making, regulatory functions, peer review, and the allocation of research funds.36.

Having come a full cycle, the life sciences evolved from being mainly government-sponsored early in this century, to being supported primarily by the private sector during the interwar period, and back to federally funded research during the postwar era, except on a radically larger scale. The probing of cells and molecules now entailed sophisticated apparatus and team-work, inflating annual institutional budgets to millions of dollars.

The intensified financial commitment mirrored the rising academic status of biology. By 1960 the life sciences had entered an era often referred to as a "golden age". Two major problems had been solved in the early 1950s: the structure of proteins, and the structure of nucleic acids, issues that have been generally regarded as essential to explaining and controlling most vital phenomena on the molecular and cellular levels. Under the new lens of molecular biology, the physico-chemical study of microorganisms had been intensified, molecular immunology had come to dominate the approach to the immune system, cancer research had emerged as a major federal goal, and neurophysiology, especially brain research, became a new frontier. American universities and scientific institutes not only played a leading role in many of these researches, but also attracted scientists from abroad; in a sense an attenuated form of the intellectual migration continued well past the war period.

While World War II was indeed a major turning point in the development of several fields in the life sciences -- notably molecular and cellular biology -- the transformations had begun at the turn of the century. Physiology, biochemistry, and to some extent biophysics were nurtured within the crusade of scientific medicine. World War I pointed up the need for biomedical research, for promoting physiology, biochemistry, and pharmacology as national resources, which in turn resulted in a commitment by the private sector to a large-scale support of research. The policy of the Rockefeller Foundation to concentrate massive funds in a physico-chemical attack on cells and molecules created a hybrid discipline-molecular biology -- that altered the intellectual and social character of biological research. The manuscript sources annotated in Part Two document major episodes within that transformation. Not all aspects of the history of the life sciences are equally well represented in this bibliography. However, taken together, these records form an important resource in mapping some of the prominent intellectual and social contours of the life sciences over a period of half a century.