Scientists and historians have often presumed that the divide between biochemistry and molecular biology is fundamentally epistemological.100 The historiography of molecular biology as promulgated by Max Delbrück's phage disciples similarly emphasizes inherent differences between the archaic tradition of biochemistry and the approach of phage geneticists, the ur molecular biologists. A historical analysis of the development of both disciplines at Berkeley mitigates against accepting predestined differences, and underscores the similarities between the postwar development of biochemistry and the emergence of molecular biology (...) as a university discipline. Stanley's image of postwar biochemistry, with its focus on viruses as key experimental systems, and its preference for following macromolecular structure over metabolism pathways, traced the outline of molecular biology in 1950.Changes in the postwar political economy of research universities enabled the proliferation of disciplines such as microbiology, biochemistry, biophysics, immunology, and molecular biology in universities rather than in medical schools and agricultural colleges. These disciplines were predominantly concerned with investigating life at the subcellular level-research that during the 1930s had often entailed collaboration with physicists and chemists. The interdisciplinary efforts of the 1930s (many fostered by the Rockefeller Foundation) yielded a host of new tools and reagents that were standardized and mass-produced for laboratories after World War II. This commercial infrastructure enabled “basic” researchers in biochemistry and molecular biology in the 1950s and 1960s to become more independent from physics and chemistry (although they were practicing a physicochemical biology), as well as from the agricultural and medical schools that had previously housed or sponsored such research. In turn, the disciplines increasingly required their practitioners to have specialized graduate training, rather than admitting interlopers from the physical sciences.These general transitions toward greater autonomy for biochemistry and allied disciplines should not mask the important particularities of these developments on each campus. At the University of Caliornia at Berkeley, agriculture had provided, with medicine, significant sponsorship for biochemistry. The proximity of Lawrence and his cyclotrons supported the early development of Berkeley as a center for the biological uses of radioisotopes, particularly in studies of metabolism and photosynthesis. Stanley arrived to establish his department and virus institute before large-scale federal funding of biomedical research was in place, and he courted the state of California for substantial backing by promising both national prominence in the life sciences and virus research pertinent to agriculture and public health. Stanley's venture benefited significantly from the expansion of California's economy after World War II, and his mobilization against viral diseases resonated with the concerns of the Cold War, which fueled the state's rapid growth. The scientific prominence of contemporary developments at Caltech and Stanford invites the historical examination of the significance of postwar biochemistry and molecular biology within the political and cultural economy of the Golden State.In 1950, Stanley presented a persuasive picture of the power of biochemistry to refurbish life science at Berkeley while answering fundamental questions about life and infection. In the words of one Rockefeller Foundation officer,There seems little doubt in [my] mind that as a personality Stanley will be well able to dominate the other personalities on the Berkeley campus and will be able to drive his dream through to completion, which, incidentally, leaves Dr. Hubert [sic] Evans and the whole ineffective Life Sciences building in the somewhat peculiar position of being by-passed by much of the truly modern biochemistry and biophysics research that will be carried out at Berkeley. Furthermore, it seems likely that Dr. S's show will throw Dr. John Lawrence's Biophysics Department strongly in the shade both figuratively and literally, but should make the University of California pre-eminent not only in physics but in biochemistry as well.101Stanley, Sproul, Weaver, and this officer (William Loomis) all testified to a perceptible postwar opportunity to capitalize on public support for biological research that relied on the technologies from physics and chemistry without being captive to them, and that addressed issues of medicine and agriculture without being institutionally subservient. What is striking, given the expectation by many that Stanley would ‘be able to drive his dream through to completion,” was that in fact he did not. Biochemists who had succeeded in making their expertise valued in specialized niches were resistant to giving up their affiliations to joint Stanley's “liberated” organization. Stanley's failure was not simply due to institutional factors: researchers as well as Rockefeller Foundation officers faulted him for his lack of scientific imagination, which made it difficult for him to gain credibility in leading the field. Moreover, many biochemists did not share Stanley's commitment to viruses as the key material for the “new biochemistry.”In the end, Stanley's free-standing department did become a first-rate department of biochemistry, but only after freeing itself from Stanley's leadership and his single-minded devotion to viruses. Nonetheless, the falling-out with the Berkeley biochemists was rapidly followed by the establishment of a Department of Molecular Biology, attesting to the unabating economic and institutional possibilities for an authoritative “general biology” (or two, for that matter) to take hold. In each case, following Stanley's dream sheds light on how the possible and the real shaped the (re)formation of biochemistry and molecular biology as postwar life sciences. (shrink)

This last result leads, rather naturally, to some concluding observations and a series of questions for further investigation. These case studies show that in all of the sites examined, the institutionalization of molecular biology as a “discipline” was primarily driven by the need to separate groups of practitioners with divergent but overlapping interests within the local context. Thus molecular biology was contingently separated from agricultural or medical biochemistry, virology, work on the physiology of nucleic acids, and so forth for contingent (...) local institutional reasons. This makes it even more pressing to try to understand how molecular biology came to be delimited on a larger scale. How did it come to be a discipline with specific intellectual content (or did it?), including some problems, tools, and practices and excluding others? How did it gain authority as the forefront biological science by the mid-1960s? We need to understand the ways in which the tensions between different practices, projects, aims, understandings of the goals of molecular biology, and so on were resolved, on what scale and in what venues, so that something approximating the political character of a discipline, rather than a federation, was achieved. If these case studies provide a sound starting point, it will nevertheless prove difficult to answer the interconnected questions implicit here satisfactorily.One means of getting at such questions that should prove of considerable interest is to examine carefully the work of those who were widely cited in the papers of the late fifties through the mid-seventies by the people now considered major founders of molecular biology. By studying the contributions of those who are now omitted in the standard histories and recollections, we will gain a clearer sense of the possibilities that were open as molecular biology took shape. It is already widely recognized that the contributions of a number of biochemists have been given short shrift, but (as the example of Ernest Gale in Rheinberger's study illustrates) there are a great many more figures whose line of work were then crucial but who are now overlooked.6 To understand both what molecular biology was at the time of its early institutionalization and what is has become, it will be enormously helpful to understand at what point the definition or ideology “hardened” and the grounds for inclusion and exclusion of individuals and lines of work were reformed. Studies of this sort are appropriate in many other areas as well, of course; in general, they should different histories, political standing, and institutional bases of those disciplines in their national cultures. It is likely (but a matter for investigation!) that such differences influenced the opportunities for introducing new bench practices, if in no other way than by delimiting the niches within which certain practices could be initiated.7 And since new practices can fail to achieve their objectives, can transform the direction of work and disciplinary allegiances of their practitioners, can lead to only routine results, or can open up important new vistas, the character of the available niches from which to work can prove to have a strong influence on the direction that new work takes if and when it starts to flourish. A key aspect of this problematic (not yet adequately studied, I believe) is the problem of drawing boundaries between different kinds of work and determining where each should fit among established disciplines and/or within some new construct. To the extent that an “international” solution is ultimately achieved to such problems, it must surely be achieved in light of initially different ways of dealing with it in different countries.Underlying work of the sort we have been exploring is the thorny problem of how best to contextualize the work being studied. This, I believe, is one of the major historiographic problems that we must face in the history of science. It is by no means a new problem, of course, but a particularization of the age-old problem of the (seeming) overdetermination of historical events. If we deal with local cultures, to understand how they develop and their fate we need to understand their location within larger cultures. But it is utterly unclear how to draw appropriate boundaries on the relevant larger culture(s). As even this brief discussion has shown, institutional cultures, the cultures of sponsoring agencies, “the” culture of science (or of biological science, physical science, etc., as appropriate), and national cultures all can provide relevant contexts, all can occasionally determine the fate of work undertaken in a particular local context. The potentially intractable problem of delimiting the boundaries of investigation looms large here, but it is one that must be faced explicity if we are to profit fully from the enormously stimulating investigations of local cultures exemplified in the four papers published in this symposium. My own view is that we have no abstract standard available for determining which boundaries are appropriate to a given study, and, indeed, that no single contextualization is adequate to the examination of any given case, but that, nonetheless, we can (at least sometimes) distinguish useful and explanatory delimitations of the larger context from others that prove to be misleading.Against this background, I hope that the four papers published in this special issue will stimulate the readers of the JHB to carry out similar studies—that is, studies that seek to characterize and contextualize local experimental cultures —over a wide range of cases. I also hope that some of those who take up this challenge will deal with the larger questions raised by the need to find a way of balancing different, sometimes competing, contextualizations of such studies. The fact that any given case requires multiple contextualizations, resulting in multifaceted representations no one of which is alone adequate, will surely land us in fascinating, hopefully fruitful and productive, controversies. (shrink)

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)

This paper investigated the part played by collaborative practices in chaneling the work of prominent biochemists into the development of molecular biology. The RNA collaborative network that emerged in the 1960s in France encompassed a continuum of activities that linked laboratories to policy-making centers. New institutional frameworks such as the DGRST committees were instrumental in establishing new patterns of funding, and in offering arenas for multidisciplinary debates and boundary assessment. It should be stressed however, that although this collaborative network was (...) based on centralized initiatives aimed at developing molecular biology as a new biological specialty, it operated above all as a nexus of practices. The main argument of this paper is that the central allocation of funds and resources, exemplified by the DGRST operation, actually enhanced the creation of a self-conscious community of biochemists turned molecular biologists by virtue of an increased circulation of tools, skills, and results that took place within the RNA network and a few analogous systems of exchange.Having hands on “things” viewed as identical for all practical purposes was a potent factor in changing the experimental systems and their meanings. Limited but shared means of doing helped to reduce uncertainties, change representations, and turn contingent decisions into meaningful choices. The collaborative enterprises then resulted in personal contacts and the transfer of skills and materials, which gradually incorporated the biochemical tools into systems producing facts relevant to molecular biology as defined by its early practitioners. In that sense, networking was a regulatory process that stabilized new research objects and acculturated French biochemists.The mere existence of such a collaborative network also changed the scale of the disciplining process. Collaborations may have been started for contingent motives, but multiple exchanges resulted in the emergence of a new collective, and amplified small displacements. Collaborations, however, worked both ways, and the RNA network may be viewed as an efficient “trading-post.” An unexpected outcome of the development of a conversion zone is the fact that, by the late 1960s, the former biochemists dominated the “new” world of molecular biology — both in terms of research habits, since interests in structural studies dominated the field, and in terms of institutional initiatives such as the creation of laboratories and institutes for molecular biology.As an example of the cognitive displacements achieved by the network, I have focused here on the stabilization of “messenger RNA” as a new biological entity. This process illustrates the role of “boundary objects” and other mediating innovations in the development of disciplinary structures. Students of science trained in the symbolic interactionism tradition have proposed that “boundary objects” enhance the multiple interactions between heterogeneous social worlds: they are robust enough to enhance unity, but plastic enough to be manipulated in different social and cultural contexts.81 Within the emerging network, messenger RNA was a weakly structured “genetic information carrier” in common use, but it could, at the same time, be a strongly structured “macromolecular structure” adapted to practical and local uses. Consequently, messenger RNA favored the association of groups of heterogeneous scientists with backgrounds and interests in medical biochemistry, genetics, physical chemistry, organic chemistry, and so forth. This contrast between general and local uses was also instrumental in integrating the manipulation of things and the negotiation of aims. In contrast to transfer RNAs, which in the French context remained objects for chemical (and mainly structural) studies, messenger RNA became a key component of the new culture of “genetic information”. Messenger RNA was a loose theoretical entity described as a “genetic information carrier” in the policy-making documents, while operational but tacit and more conflicting definitions prevailed at the bench. In other words, messenger RNA was not only a classical “boundary object” but also a “flag object,” which tightened the collaborative network by mediating between the DGRST offices and the laboratories. (shrink)

The convergence of developmental biology — embryology — and molecular biology was one of the major scientific events of the last decades of the twentieth century. The transformation of developmental biology by the concepts and methods of molecular biology has already been described. Less has been told on the reciprocal transformation of molecular biology on contact with higher organisms. The transformation of molecular biology occurred at the end of a deep crisis which affected this discipline in the sixties and seventies (...) and which led to a cruel criticism of the preexisting models of gene regulation. Numerous new, sometimes heterodox, models were proposed to describe the level at which gene regulation took place and its underlying mechanisms. The crisis resolved itself at the beginning of the eighties with the rapid accumulation of results from genetic engineering techniques and, above all, a displacement of the descriptive level from the molecule to the cell. This displacement gave molecular biologists the 'explanandum' which had been cruelly lacking during their initial study of higher organisms. The new molecular cell biology is an interfield explanation of living phenomena, relating a description and an interpretation localized at different levels of organization. (shrink)