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Sydney Brenner and Biotechnology

by Antoinette Sutto

Table of Contents

Introduction
I. Monsters and mutants? The controversy over recombinant DNA
II. Chromosomes and Consultancies
III. Philip Morris
Conclusion
References

Introduction

Dr. Christopher Booth, the director of the Clinical Research Center, an organization under the umbrella of Britain’s Medical Research Council, wrote to Sydney Brenner in March of 1980 to ask him about biotechnology. Specifically, he wanted to know what it was. Booth had been contacted by a government committee drawing up a report on biotechnology in Britain, “and we found it somewhat difficult to determine precisely what biotechnology is.”1

Booth was right to pose the question, and he was not wrong to direct his inquiry to Brenner. Biotechnology had become a buzzword by 1980. The event that is usually said to have set off the “biotech revolution” of the 1970s was the development by Herbert Boyer of the University of California San Francisco and Stanley Cohen of Stanford of a process through which DNA from one species could be inserted into and replicated in another, i.e. recombinant DNA technology. Boyer and Cohen made their discovery in the early 1970s. In 1974, their respective institutions applied for a patent on this technology, which was granted in 1980. Boyer and Cohen’s work — and the patent on it — were part of a broader trend. The same year that the patent for recombinant DNA was granted, the Supreme Court decided the patent case of Diamond vs. Chakrabarty in favor of Ananda Chakrabarty, a biochemist working at General Electric who had developed a bacterium which could break down crude oil. This case established that genetically modified organisms could be patented.2 Across the Atlantic, researchers in Great Britain developed the technology to produce monoclonal antibodies, although they did not patent it.3 Finally, just a few months after Booth wrote to Brenner, the American company Genentech — one of whose founders was Herbert Boyer — went public with astounding success. By the early 1980s, investors all over the world were itching to move capital into this new and exciting field. Indeed, indeed the context of Booth’s letter was an effort on the part of the British government to create a connection between research laboratories and investors which would allow the commercial exploitation of researchers’ discoveries. All of this raised concerns about both the new technology itself as well as how to structure the interface between academic research and investment capital that the commercial exploitation of biotechnology made necessary.

Historians of science have offered a variety of perspectives on how to define biotechnology and how best to understand the scientific and cultural changes that accompanied the biotech boom. Especially for scholars writing in the 1970s, 80s and early 90s, when the discovery of recombinant DNA still fresh in everyone’s minds, it was easy to be dazzled — or rendered profoundly uneasy — by the promise and the potential dangers of recombinant DNA. Was this a revolution in biology? Many observers at the time, including scientists and historians of science, thought so. Or did biotechnology have a longer history in which the discoveries of the 1970s were turning points, but perhaps not enough to constitute a revolution? Did “biotechnology” mean simply “recombinant DNA” or should the concept be more comprehensive?4 After all, humans had been modifying organisms for their own purposes for thousands of years, gaining an enormous amount of applied microbiology expertise in the process. Japan, for example, was seen as a biotechnology center in the 1970s because of its strength in industrial fermentation; this technology did not make use of the genetic engineering discoveries of that decade.5

And in terms of the science alone, it is worth emphasizing that Cohen and Boyer’s discovery didn’t come out of nowhere. The idea that it might be possible to cut and splice DNA had occurred to many biologists by the late 1960s, and by the early 1970s a number of groups were working on the same fundamental idea: “obtaining a well-defined piece of DNA,” then “attaching this piece of DNA” to a vector of some kind “to carry the foreign DNA into a living cell.”6 The concern that what might be possible through this kind of research could have devastating consequences for humans and their environment was already a topic of discussion in the 1960s — the term “genetic engineering” was coined then, not later.7

At the same time, the 1970s and early 80s remain a turning point scientifically and, as numerous scholars have pointed out, culturally. The relationships of scientists and universities to industry changed significantly. In particular, how researchers thought about patents and licensing changed. As Soraya de Chadarevian has pointed out about the “failure” of British researchers to patent the procedure for monoclonal antibodies in the 1970s, for example, “Britain was not in a ‘patent culture’ in the 1970s.”8 The situation in the United States was similar. Sally Smith Hughes has argued that although there were certainly continuities with the past in terms of commercial exploitation of biological research, the Cohen-Boyers patent fundamentally altered the landscape. “The patent became an agent in the transformation of molecular biology from a predominantly academic discipline to one with pervasive practical applications and industry connections. This patent history sets the stage for a shift in attitude and research emphasis in molecular biology in the 1980s toward a focus on applications, extensive interaction with the commercial world, and a resultant blurring of boundaries between academia and industry.”9 Daniel Kevles has made a parallel argument about Diamond v. Chakrabarty, which was decided in 1980. In his view, this Supreme Court decision “seemed in many quarters to link the making of money to the making of monsters, or, at least, to manipulation of the essence of life.” In so doing it brought into patent law a host of moral and ethical questions with far-reaching consequences.10

The history of biotechnology during this period also needs to be understood in the context of the larger political and economic situation. While histories of biology and genetics might give the impression that specific scientific discoveries were the main drivers of all this change, there was a political and economic push as well as a scientific pull. In Japan, for example, the post-WWII industrial boom had led to dangerously high levels of industrial pollution, which spurred an interest in new, cleaner, or perhaps even cleaning microbiology technologies. The oil crisis of the 1970s, which brought increased energy costs, also played a role. A similar dynamic was at work in Germany — the West German “economic miracle” of the 1950s and 60s had had a profoundly negative effect on the environment. This spurred interest in biotechnology, which was understood to be cleaner technology.11

Across the board, economic thinkers in wealthy countries feared that the old industrial economy had peaked. The interest in biotechnology in Britain, for example, was “colored by the legacy of the country’s Great Power and imperial status, which left the country with disproportionately large government research institutes, with its great oil and chemical companies now seeking to diversify, and with a national obsession over economic decline counterbalanced by hopes of technological greatness.”12 In the United States, federal policy on biotechnology changed substantially between the 1970s and the early 1980s. While the government earlier on expressed caution about new techniques in biotechnology — as evidenced in the 1976 NIH guidelines on recombinant DNA research — the Reagan administration was focused on economic growth and sought to encourage “collaborations between universities and industries,” especially in new and promising areas like biotech. This was backed up by legal changes, e.g. the Bayh-Doyle Act (1980) “which gave universities the right and incentive to hold patents on inventions arising from federally funded research.” The concern about potential biohazards which had been so prominent in the early 1970s faded away, and “by late 1980…the NIH guidelines had been weakened to the point of virtual dismantling.”13 Scientific discovery alone did not drive change — government policy and broader economic trends were behind a significant amount of the interest in exploiting biotechnology.

Biotechnology, in other words, is a slippery term. It predated the biotechnology boom itself by decades and can be understood in both a broad, long-term sense — the discovery that yeast makes bread rise is a form of biotechnology, and the applied microbiology used in industry and food production by the twentieth century certainly is as well — and a narrower sense, focusing on the newness of the technologies developed in the 70s and 80s and their impact on public health, public perception of science, and the relationship of research institutions (and researchers) to industry. And, as recent scholarship has pointed out, the political, economic and cultural context in which scientific discoveries are made plays a crucial role in how those discoveries are understood and applied.14

When Booth asked Brenner what specifically biotechnology was, he asked a very good question. We don’t have a record of Brenner’s reply to his colleague, but if anyone was in a position to offer an answer, it was Brenner. Sydney Brenner (1927-2019) was among the most influential molecular biologists of the twentieth century. He made a number of significant contributions to the field of molecular biology in the 1960s, including (in collaboration with Francis Crick and colleagues at Caltech and the Institute Pasteur in France) the discovery of messenger RNA, and established C. elegans, a tiny roundworm, as a model organism for studying genes and proteins. He and two colleagues were awarded the Nobel Prize in medicine in 2002 for their work on genetic regulation of organ development and programmed cell death, much of which was based on the work on C. elegans. The professional context in which Brenner worked was important too. Brenner joined what became the British Medical Research Council’s Laboratory of Molecular Biology (LMB) in the late 1950s and served as its director from 1979 until 1986; he worked in a laboratory unit distinct from, although located in, the LMB until he retired in 1992. Research done at the LMB by Brenner and others played a key role in the development of molecular biology in the 1950s and 1960s. The lab was the scene of a number of discoveries key to the biotech revolution in the 1970s, including César Milstein and Georges Köhler’s discovery of monoclonal antibodies in 1975. Because it was a Medical Research Council laboratory (the Medical Research Council is a British government agency that coordinates and funds medical research), Brenner as its director was engaged not just in the science of the biotech revolution but also in the politics of how the new scientific discoveries were to be exploited and the debates about the effects this would have on the process of science itself.

This essay will use Brenner’s career to explore two key moments in the history of biotechnology: the debate about the safety of recombinant DNA in the 1970s and the partnerships between research institutions and industry that formed the core of the biotechnology boom in the late 1970s and early 1980s. It will also examine an additional case that draws on many of the themes present in the first two, Brenner’s collaboration with Philip Morris to found a molecular biology research institute in the 1990s. What emerges from this exploration is a portrait not only of how quickly the field of molecular biology changed over the course of several decades, but how it changed — how scientists, administrators, investors and to a certain extent the public navigated this brave new world. The essay will highlight the relevance of the Sydney Brenner collection at CSHL to scholars interested in contributing to the history of biotechnology — the themes and material addressed here by no means exhaust what is available in Brenner’s papers.

I. Monsters and mutants? The controversy over recombinant DNA

Some of the first experiments in genetic engineering were conceived by Stanford biochemist Paul Berg in the early 1970s. It was the success of a series of experiments by Stanley Cohen and Herbert Boyer, however, that pushed recombinant DNA into the limelight. Cohen and Boyer’s idea was first hatched during informal conversations at a conference in Hawaii in November of 1972. They began their experiments soon after, and by early 1973 it was clear that their technique worked. They shared their work at a Gordon Research Conference that summer, and the following November they published a paper. The research was striking enough to make the front page of the New York Times six months later in May of 1974.15 As historian of science Doogab Yi has pointed out, while Cohen and Boyer received most of the attention, the work of many others, particularly Paul Berg, was crucial to this discovery. Although what they did was very significant, Cohen and Boyer benefited from a certain amount of hype, some of which they generated themselves.16

Was this research potentially dangerous? Paul Berg hadn’t thought so, but some of his colleagues at Stanford, including molecular biologist Joshua Lederberg, were not so sure; Lederberg’s misgivings had been enough to make Berg put his experimental program on hold. The fact that it was not entirely clear whether recombinant DNA experiments posed a threat to laboratory staff, the general public or the environment led a number of researchers to convene a meeting at MIT in April of 1974 that resulted in a letter published in Science, Nature and the Proceedings of the National Academy of Sciences. This letter called for a moratorium on further recombinant DNA experiments until it could be determined that they were safe.17 In the letter, the authors — Paul Berg, David Baltimore, Boyer, Cohen, James Watson, Norton Zinder and others — described some of the potential risks. For example, E. coli bacteria were used “to clone the recombinant DNA molecules and to amplify their number.” Given that “strains of E. coli commonly reside in the human intestinal tract, and they are capable of exchanging information with other types of bacteria,” it was possible that if people came into close contact with modified E. coli, “new DNA elements introduced into [the modified] E. coli might possibly become widely disseminated among human, bacterial, plant, or animal populations, with unpredictable effects.” The authors were at pains to note, however, that their “concern was based on judgements of potential rather than demonstrated risk.” That is, these dangers at this point were hypothetical. Indeed, nailing down precisely what, if any, dangers recombinant DNA might pose was itself a challenge.18

The call for a moratorium in the United States led to a discussion of the issue in Great Britain, where the Medical Research Council decided to “order an immediate freeze on all recombinant DNA experiments in Britain.” The British government convened a commission headed by plant physiologist Eric Ashby to address the issue. Brenner was not among the members of the so-called Ashby Working Group, but he did contribute a detailed white paper emphasizing the significance and potential of recombinant DNA. Brenner had been taken aback months earlier when he had received a letter from the MRC requesting him to comply with the moratorium, and in his white paper argued forcefully that banning this type of research “would be a disaster, since it would deny us access to the very scientific knowledge we urgently need.”19

Concerned that the British might gain control of the conversation about this issue, Berg organized a meeting in Asilomar, a conference center at Monterey Bay, California, to address it. He had read an early version of the Ashby report, was aware of Brenner’s role in it, and was eager for him to participate in the Asilomar meeting.20 When he wrote to Brenner in September of 1974 to invite him to be on the organizing committee, Berg emphasized that the conference needed to be “international in its representation and impact.” Scientists from outside the US should be “involved in both organizing the meeting and, more importantly, in generating the recommendations that come from the conference.” He asked Brenner to suggest people from Britain and Europe to invite and — more importantly — to help put together conclusions from the discussions at the conference and draw up a set of recommendations for this type of research.21

The Asilomar conference itself has gone down as a turning point in the history of genetic engineering research, particularly with reference to the relationship between scientists and the public. Scientists, administrators and other individuals who had reason to be professionally involved in or concerned with recombinant DNA research in the 1970s have emphasized its significance and attributed to it an importance that went far beyond the practical utility of the safety protocols for recombinant DNA research that the conference developed.22

And Brenner’s participation was key, as a handwritten letter to him from Berg after the conference attests. Berg expressed deep appreciation for Brenner’s “magnificent contribution” and for his “wisdom[;] your comments and ideas and ideas and certainly your humor rescued us on several occasions when we floundered.”23 Berg’s letter also points to some of the ambiguities of the Asilomar conference. When he thanked Brenner for his contribution, he called it a “contribution to the conference’s outcome (success?)” He also suggested that his own perspective on the conference, which had been a month previous to the date of the letter, had shifted, although he did not say how.

What, then, was the significance of the Asilomar conference? If it was a success, on whose terms? Did it deserve the importance given to it in hindsight?

One document in the Brenner collection at CSHL archives that throws light on some of the issues at stake is an “Open letter to the Asilomar Conference on Hazards of Recombinant DNA” from the Genetic Engineering Group of Science for the People, which was made up of individuals affiliated with Harvard Medical School, MIT and Boston University. The writers’ position on science and scientists points to part of the wider public context in which the Asilomar conference took place. By the early 1970s, the Cold War and the nascent environmental movement had left a significant proportion of the population, including some academics and scientists, with doubts about the value of some forms of scientific research and suspicions about who ultimately benefited from it. In their open letter to Asilomar, of the first things the writers did was to argue that many promising and exciting discoveries of the past turned out to have terrible unforeseen consequences. Here they cited the “tragic results already caused by, for example, radium, asbestos, thalidomide, vinyl chloride and dieldrin” (this last is a pesticide that is toxic to humans and animals). Scientists, they implied, were not necessarily in a position to judge the potential effects of their own work. Moreover, they continued, it was not clear that this work “[arose] from social or medical needs of large segments of the population” or that it would address any problems outside of the narrow research concerns of molecular biologists. The result of this was that “that experiments that happen to be conceived, get done, regardless of whether or not they should be done.”

In other words, the writers of the letter questioned scientists’ ability to judge risks, take the needs of the public into account, and regulate themselves accordingly. They even implied that the reason for this was not naiveté but rather greed: to assume that “the molecular biology community…is capable of wisely regulating this development alone…is like asking the tobacco industry to limit the manufacture of cigarettes.”24 This is quite a comparison, since the tobacco industry was and is known for suppressing research showing that its products are a health hazard. It is difficult to determine how far the writers intended this comparison to be taken. In 1975, the commercial applications of recombinant DNA were imaginable — Stanford and UC had applied for the patent on Cohen and Boyer’s methods a year before, after all — but not yet real. The comment indicates either a startling prescience about the commercial viability of genetic engineering or a profound distrust of molecular biologists’ ability to place public safety above publishing papers, or perhaps both.

The Genetic Engineering Group of Science for the People, then, distrusted the molecular biology community’s willingness and ability to regulate itself and did not think that the scientists doing the research were in a position to make valid judgements about its dangers. They argued that “decisions at this crossroad of biological research must not be made without public participation.” Yet this was not what they saw happening at Asilomar. Rather, “we see even in the structure of this conference that a scientific elite is here alone trying to determine the direction that such regulation should take.”25

The “Open letter to Asilomar” points to one of the fundamental points of conflict about the Asilomar conference: the question of what it was, or should have been, about. The writers of the letter wanted a conversation about the bigger picture, with public involvement and a debate about who benefitted from this type of research and whether it should be done at all. There were a number of journalists in attendance who were thinking along similar lines; one of them in fact got into an altercation with Sydney Brenner over whether journalists should be allowed to record parts of the conference that the participants preferred to keep off the record. In Brenner’s recollection “the man went berserk — accusing me of being a fascist and so on.”26

A discussion fully open to the public was not what the organizers wanted, and it was not what happened. The problem was not that Brenner, Berg or anyone else were fascists or that they were harboring secret plans to hatch armies of Frankenbugs in the interest of getting a profitable patent or a Nature paper. Rather, the issue was that the scientific community, although not in full agreement about the hazards, tended by 1975 to believe that the risks of recombinant DNA research were being over-hyped in the press. The goal of the Asilomar conference was not a long public debate over the merits of the research itself. Rather, the goal was quite narrowly focused: to arrive at a set of guidelines for proceeding with this research that would demonstrate researchers’ responsibility and commitment to safety and thus head off any attempts at outside regulation of recombinant DNA research by the federal government. They reached consensus on the content of their suggested guidelines, which were published shortly after in Science and PNAS.27

Asilomar in this sense is similar to other lesser-known meetings convened by scientists in the late 70s to discuss the potential hazards of recombinant DNA in the light of the federal guidelines issued by the NIH in 1976 (these guidelines originally placed substantial limits on rDNA research, including its commercial application, but were soon weakened). Like Asilomar, these later conferences were intended as closed meetings of professionals rather than open public debates, and the organizers had a tendency set up the discussion so as to exclude certain issues and push toward specific outcomes: “reservations about claims for decreased hazard were for the most part organized out of consideration, whereas claims that certain types of risk were minimal were organized in.”28 In this sense, Asilomar and subsequent meetings about recombinant DNA are relevant not only for their importance to the history of molecular biology, but also for the sociology of science in a broader sense, since they offer a glimpse into how the scientific community addressed the partly scientific, partly political problem of how to assess and communicate risk to a non-scientific audience.

Another key issue that was brought to the fore by Asilomar was the question of what kinds of issues scientists considered their responsibility to address. The conference’s focus on “epidemiological risks and laboratory safety issues” had the effect — whether intended or not — of “[contributing] to the marginalization of further issues, such as the ethical and commercial aspects of rDNA technology.”29 Indeed, some researchers who were in the field at the time (but who did not necessarily attend the conference) have argued that there appeared to be a blind spot about the importance of issues beyond technical matters and safety protocols. One immunologist, interviewed decades later, thought that the conference

did little or nothing about the impact of big-business-driven biotechnology on the universities and society in general…I think Asilomar really downplayed the real social problems that had inevitably arisen as part of the emergence of biotechnology and a profit-hungry industry behind it, and it didn’t help in that respect.30

The immunologist’s comment may be colored by hindsight to a certain extent, since in 1975 the huge boom in biotechnology and the concomitant transformation of the relationship between researchers and industry lay mostly in the future. Moreover, had the organizers of the conference decided to hash out the social and ethical issues that recombinant DNA and its commercial exploitation brought with it, they might not have achieved their primary goal of agreeing on a regulatory framework.31 At the same, it is worth asking why there seemed to be a lack of interest in addressing broader questions. In the course of a discussion about Asilomar years later, in February of 2000, in which the original organizers participated, it emerged that “the meeting’s organizers [had] decided not to address ethical issues surrounding genetic alteration but to stick to safety issues they felt they could address as scientists.”32 The comment implies that the scientists organizing the meeting considered some the broader social or moral issues as beyond their professional purview or perhaps outside their area of responsibility. Brenner may have been speaking for both himself and others when he said years later that he didn’t believe that scientists, as a group, had “some special responsibility” that went beyond their responsibilities as human beings.33

What is the significance of the Asilomar conference in the context of Brenner’s career and the development of biotech in the 1970s and 1980s? Asilomar, along with the debate both then and later over what that meeting represented, or what it should have been or could have been, illuminates a specific historical moment in the history of biotechnology. The conversation at Asilomar took place largely among academic biologists with no ties to industry. Within a few decades, such a group would have been impossible to convene, since “today most senior academic researchers have ties to biotechnology companies that would complicate any attempts at self-scrutiny.”34 This meant that a debate over commercial applications or corporate ties would have made little sense, or, had it taken place, would have remained highly theoretical. Brenner in this sense was representative — like most of his colleagues, he did not (yet) have extensive ties to a biotech industry which in any case was still in its very early stages. For him and a lot of other molecular biologists, this would change dramatically within a few years. The conference also took place at a time, 1975, when there was still significant public concern about the dangers of genetic engineering, even though most biologists were or would soon be convinced that the risks were not so dramatic as some had imagined. The documents on Asilomar, including those produced by or directed to Sydney Brenner, offer a look into the concerns and assumptions of a community of scientists right at the beginning of a significant change in their professional and intellectual world.

Finally, the Asilomar conference brought to the fore the question of whether, when and how researchers should discuss their work with laypeople. The aspect of this that was specific to recombinant DNA was the question of how to deal with a widespread public perception of danger in a case where the danger might actually be minimal; researchers were concerned that addressing such a perceived danger might have the unintended effect of reinforcing the idea that the danger was real. Paul Berg alluded to some of these public communications challenges in a letter to Brenner when he mentioned his own visit to England to appear in a BBC debate “on the matter of our recent letter to Science and Nature concerning synthetic recombinant DNA molecules.” Berg did not think there had been “that much of a debate,” an opinion “shared by others who attended,” but thought that “perhaps the public seeing the program will find a bit of the controversy that was there at the beginning.”35 Berg was probably referring to his own experience in the early 70s, when it was really not yet clear how much of a safety risk recombinant DNA experiments might pose. Another biology professor who was interviewed years later about Asilomar thought that raising questions in a public setting about larger issues had “boomeranged,” because it “made people suspicious for the sake of needing to become suspicious.” That is, scientists’ willingness to talk about potential risks reinforced the idea that the risks were there and that they were significant, even if that was not necessarily the case. More than that, it led the general public to conclude “that they should have some say in the decision-making.”36

As that biologist’s comment implies, issues of communication were linked to issues of responsibility — to whom, if anyone, were researchers obligated to render an account of what they were doing? Who got a say about whether research was justified or permissible? As historian Sheldon Krimsky put it in his history of the controversy, “Who gets the benefits and who bears the risks?”37 In the case of recombinant DNA and genetic engineering, these questions were further complicated by the dramatic shift that would soon happen in who was paying for a lot of this research and who hoped to gain from it.

II. Chromosomes and Consultancies

Perhaps the most important cultural shift for scientists engaged in recombinant DNA and other related genetic and molecular biological research in the 1970s and early 1980s occurred in their relationship to industry. More and more professional researchers took on consulting work for biotechnology companies or even founded such companies themselves. The barrier between academic research and industry became very porous. This had its advantages, including technology transfer from laboratories engaged in basic research to companies ready to find commercial applications for that technology. Many professional scientists also found new sources of research funding through this new relationship and some personally made a great deal of money, either through consulting fees or having their names on the patents for commercially exploitable discoveries.

How did this new constellation of economic, professional and personal connections work in practice? It sounds straightforward: researchers collaborated with biotech startups and large pharmaceutical companies to move innovative discoveries into the marketplace. But this relationship was new for everyone involved and the details had to be worked out on a day to day basis. It wasn’t always straightforward — logistically, legally, or in terms of professional ethics.

Brenner did a significant amount of consulting work for biotech firms in the 1980s. His correspondence, along with other related materials in the CSHL Sydney Brenner collection, illustrates the challenges faced by scientists working as consultants. Specifically, the collaboration between the Medical Research Council (Brenner was head of the MRC’s Laboratory for Molecular Biology) and Celltech in the early 1980s is well documented enough to allow for an in-depth exploration of the researcher/consultant-biotech company relationship during the biotech boom of the late 70s and early 1980s.

What was Celltech? It was a biotechnology company conceived with the goal of “reproducing in this country [the UK] the sort of small entrepreneurial ‘high technology’ laboratory (to operate in the area of recent developments in molecular and cell biology) that are now very much part of the American way of life,” according to MRC administrator Tony Vickers writing to Christopher Booth in March of 1980, when the project was still in the planning stage.38 Interest in biotech on the part of large corporations and investors had grown significantly by the late 1970s.39 In June of 1980, just months after Vickers described the Celltech project to Booth, the Supreme Court decided in favor of the Chakrabarty patent in the United States; this decision meant that other biology-related patents like that of Cohen and Boyer could be approved.40 And in October — just a month before the Celltech project was formally launched — Genentech would have their spectacular IPO. Biotech was booming and the British, as Vickers’s letter suggests, didn’t want to be left behind by the Americans.

But Celltech was distinct. It wasn’t a typical private biotech start-up. Rather, it was the brainchild of Britain’s National Enterprise Board (NEB), which had been founded in the mid-1970s to spur British industry and promote economic growth. Celltech had a significant amount of private funding — in addition to the NEB, its founding shareholders included a number of large private companies, and more than half of its £12 million capital came from the City, the British equivalent of Wall Street.41 Crucially, Celltech also enjoyed a special partnership with the Medical Research Council and its laboratories — including the Laboratory of Molecular Biology (LMB) of which Brenner was the director.

The agreement between Celltech and the MRC gave Celltech “the right in the first instance to exploit commercially all discoveries made in MRC facilities [which included the LMB] or otherwise the property of MRC, provided that these” discoveries fell into one of the categories listed in the agreement, including “recombinant DNA, cell fusion,” and “monoclonal antibodies.”42 As the science editor of the Financial Times later commented, this relationship with the MRC was a “coup” on Celltech’s part, since it gave them “exclusive access to all research on monoclonal antibodies in the laboratories and units of the MRC.” The MRC was “a government funded research operation, costing the taxpayer more than £100m a year.”43 Celltech’s investors, in other words, had an opportunity to profit enormously from publicly funded research.

Initially, it remained open what the ultimate scope of the Celltech-MRC collaboration would be. A Nature article published in June of 1980, while the project was still in the planning stage, described it as a “commercial biotechnology venture” focusing on the commercial exploitation of monoclonal antibodies in which three different laboratories would participate: the LMB, the laboratories of the Imperial Cancer Research Fund, and Cold Spring Harbor.44 The inclusion of CSHL is interesting, since the Celltech project was intended specifically as an economic driver for the British biotechnology industry — how did an American lab fit into that picture?

Correspondence between Brenner and others at the MRC about the project sheds some light on the potential collaboration and why it ultimately did not come to fruition. Brenner wrote to Vickers on 20 February 1980 to let him know confidentially that he had spoken to Jim Watson on the phone the previous day. Watson had been “enquiring in a very general way whether some association between Cold Spring Harbor Laboratory and ourselves would be possible in relation to the exploitation of monoclonal antibodies. They have been developing a number of reagents against structural components of cells.” Brenner thought that these reagents were research- rather than commercially oriented, but “some may have wider application.” Rumors of the Celltech project had reached Watson, and Brenner had confirmed that “we are involved in the exploitation of monoclonal antibodies,” but he had been cagey on further details and did not “mention the NEB.” He had told Watson that he would bring the matter up with Vickers and “ask whether you [Vickers] and/or the NEB see any interest in having an American connection; I can see many advantages but there may be problems.”45 There are a few pages of notes taken by Brenner a few days later during a phone call with Watson about monoclonal antibodies, and some from another call with CSHL assistant director Joe Sambrook about the NEB/Celltech project — evidently the information about the NEB’s role had gotten out, even though Brenner hadn’t said anything about it to Watson. He noted that he had spoken to Vickers on February 27 about “the Cold Spring Harbor situation,” noting that “the commercial collaboration needed to be worked out by NEB; the question of scientific collaboration could be left until later.”46

In the end, it didn’t work out. Watson ultimately decided that it would be better for CSHL to “go it alone and form our own company.”47 The NEB may also have played a role in the decision not to pursue a collaboration — Brenner’s letters do mention potential problems with an American connection, although he does not specify what those were. It is also worth emphasizing that even this brief transatlantic discussion about collaboration shows how the commercialization of molecular biology was shaping how scientists worked together: Brenner noted that the commercial aspect of the collaboration would have to be worked out first, while the scientific part could wait until later.

Once the scope and form of the Celltech-MRC collaboration had been determined and the project was operating, it was necessary to figure out how the scientific collaboration would work in practice. For example, Brenner made an effort to ensure that industry scientists had in-person contact with their MRC counterparts. In June of 1981, he suggested that scientists from Celltech as well as ICI, Unilever and Wellcome be invited to the LMB’s annual laboratory symposium, because “this could create very useful links with these groups.”48 And work on collaborative projects between Celltech and MRC was moving forward, as evidenced by the project status descriptions in a review of the progress of the collaboration dated 5 November 1981.49 At the same time, there was some frustration on the part of scientists about what they saw as Celltech’s failure to fulfill its mission. César Milstein expressed annoyance about the company in a letter to Brenner in April of 1981, arguing that Celltech was failing to think in the long term and “failing to develop the link we are interested in, namely, their ability to take a nascent commercial star into the development stage and away from us.” He was irritated with the “Celltech technocrats” who needed to work harder to “see the problem as we see it.”50 Brenner shared Milstein’s concerns that Celltech did not appear to be doing what it had promised to do, and noted that “there is dissatisfaction in the laboratory about the relationship and…doubts not only about Celltech’s intentions and technical ability but also about its commercial expertise.”51

The collaboration with industry also created challenges related to how to categorize individual scientists’ contributions to a given project and how to categorize projects in terms of their relationship to the MRC-Celltech collaboration — the giving and receiving of scientific advice, for example, could prove tricky. An instance of this problem occurred in the fall of 1981, when Brenner contributed to a project relating to insulin. His contribution was advice and expertise rather than laboratory work, and although it was based on work done in MRC labs, it was not clear whether the advice was coming from Brenner in his role as a private consultant to Celltech, or Brenner in his role as an MRC staff member. As Charles Kirkman of the MRC described it to Celltech, “we have the problem of deciding what actions they [MRC scientists] are taking under their consultancies and when they are acting for the MRC under the Research and Marketing Agreement,” i.e. the legal framework for collaboration between Celltech and the MRC. The distinction mattered, because advice given by an MRC employee in the capacity of a private consultant was regarded by Celltech as Celltech property, and MRC would receive no benefits under the Research and Marketing Agreement, even if the advice was based on experience in an MRC lab. Kirkman thought that the MRC had been allowing this to happen too often, and that in this particular case, “the company might recognize Dr. Brenner’s intent that he was acting for the MRC and that, if this ever comes to commercial exploitation, there should be at least a nominal consideration to the MRC so that this goes on the record as part of the MRC’s help to Celltech.”52 In the context of a collaboration with industry, scientific advice was not simply scientific advice — it was a product with value and ownership had to be determined.

Along similar lines, a research project might be straightforward in scientific terms but very complicated when it came to how to situate it within the legal framework of the collaboration. For example, in the summer of 1981 Brenner was working on a new immunoassay method with potential commercial value. This “method could be used with ordinary antibodies and does not need monoclonal antibodies although using the latter would be of distinct advantage,” he explained. The MRC-Celltech agreement specified a collaboration to develop research based on several specific biotechnologies, including monoclonal antibodies. Because Brenner’s new method didn’t strictly require the use of monoclonal antibodies, it seemed to Brenner that it lay “outside the Celltech agreement. However, a proprietary unique method of assay taken together with monoclonals would seem to be a good basis for commercial exploitation and the method may therefore be valuable.” The project required “feasibility studies” which “will take time and require additional people,” so outside funding would be useful. If Brenner and his LMB staff did “this work with our own resources and it is successful it will automatically belong to the NRDC.” In his view, “it would be a pity to have that happen simply by default.”53 (The NRDC, Britain’s National Research Development Corporation, was a government agency tasked with technology transfer from the public to the private sector. Researchers in Britain generally did not express great enthusiasm about using it as a vehicle for technology transfer.54)

What would be the best way forward for this project? Brenner saw several options. One was to “give this to Celltech as a Category C proposal.” Category C included discoveries that were made in MRC labs but which were funded entirely by Celltech. It was not clear from the MRC-Celltech agreement, however, whether this project would fit in that category. Brenner was also “not certain whether Celltech has the resources to develop and exploit this work.” Another option “would be to put this to Unilever for funding and with some exclusivity to develop and apply the results in the event of success.” There were plusses to that idea, “but I do not know whether we should, or need to, involve the NRDC or Celltech or both in such an arrangement.” In any case, it would be necessary to have a thorough discussion before going any further with the project.55 Brenner’s description of the issues here highlights a change in how researchers thought about their projects. The collaboration between the MRC and industry required scientific projects to be placed not only in their relation to previous and future research — if they were potentially commercially viable, they also had to be placed into an additional framework created by the legal relationships between the MRC, Celltech, and possibly other companies. This second framework often determined whether and how a specific project might be funded and move forward.

This new framework was not static. Experience revealed that some tinkering was required. For example, the Celltech-MRC agreement limited MRC scientists’ ability to accept funding from charities and international agencies, and in early 1983 there was some discussion of how the agreement might be altered to allow for this.56 There were also some legal hiccups and professional ethics questions to address. Especially for projects that did not precisely fit into the agreement as it already stood, it could be challenging to draw up an appropriate framework for a collaboration even when both parties were interested. Brenner’s immunoassay project (mentioned above) fell into this category. Celltech’s chief executive Gerard Fairtlough initially drew up a draft agreement between Brenner personally and Celltech. Charles Kirkman of the MRC immediately flagged this as “quite inappropriate,” and Brenner, too, agreed that it was “not proper to make this agreement with me personally.”57

A larger ethical problem became evident in the relationship between MRC scientists and Celltech’s Science Council, the body that provided Celltech with scientific advice and strategy. MRC scientists, including Brenner and César Milstein, sat on this council as scientific consultants. This led to a series of potential ethical conflicts that made it clear by 1981 that Brenner and Milstein would have to resign from their positions on the council. Gerard Fairtlough outlined the situation in a draft statement to the press, noting that experience in the first year of the Celltech-MRC collaboration had shown that there was a need for greater clarity in everyone’s roles within the collaboration. Celltech had “benefitted greatly from the advice of its Science Council,” and “in giving this advice, the members of the Council should have Celltech’s interests in mind.” That is, when MRC scientists who sat on the Council were giving advice in that capacity, it was understood to be for Celltech’s benefit. But then Fairtlough got to the core of the issue: “for those members of the Council who are senior MRC staff involved in collaboration with Celltech, this can give rise to confusion about roles.”58 In other words, senior MRC scientists like Brenner and Milstein who were working on joint MRC-Celltech projects and giving Celltech scientific consulting advice were in an awkward position because it was not always clear whose interests they represented.

The consulting relationship between senior MRC scientists and Celltech would have to change. Brenner and Milstein both resigned from their positions on the Science Council. But no one wanted to cut consulting ties entirely; Celltech naturally wanted to continue to make use of Brenner’s expertise. Fairtlough proposed that Brenner “become a Special Consultant to Celltech” after leaving the Science Council. But Brenner saw immediately that this “relationship proposed by Gerard [Fairtlough] would put [him, Brenner] in the same ambiguous position as [his] membership of the Scientific Council.”59 Ultimately, late in 1981, the MRC and Celltech created an “umbrella agreement” which was intended to clarify the collaboration between Celltech and Brenner’s lab, the LMB. It was to include “an administrative framework for projects, provide funds for two post-doctoral positions, and cover the advice and guidance which Dr. Brenner and other senior LMB scientists would give to the collaborations and to Celltech generally.”60 This change created a minor PR problem, since the departure of the two researchers from the Science Council might make it seems as if there had been a breach in MRC-Celltech relations, which could “lead to adverse publicity.”61 In the end, though, the public relations effects of this change in policy were not disastrous.

The primary significance of Brenner and Milstein’s departure from the Celltech Science Council and the development of the “umbrella agreement” in the fall of 1981 was to make clear how difficult it was to square 1) the consulting role played by MRC scientists and the relationship between Celltech and MRC scientists that was necessary for the partnership and 2) the norms of professional ethics. Indeed, the issue went beyond the potential conflict of interest outlined above. Brenner’s complicated relationship with Celltech had also had an effect on his staff at LMB, who needed reassurance that “the Director of the Laboratory had undivided loyalty to LMB and the [Medical Research] Council and that his services to Celltech were to further those interests.”62 In a memo to his staff dated 30 October, 1981, Brenner revealed how much discontent there in fact was. Part of the problem was rooted in European patent law, which stipulated that any prior disclosure of research results, including the publication of a paper or even giving a talk, invalidated any subsequent patent claims. For this reason, Brenner had “asked to see the abstracts of all manuscripts as early as possible” before publication, which “[gave] rise to disquiet” and claims that “the whole system represents an interference with scientific freedom.”63 Brenner ultimately backed down on the requirement that all staff submit research for review and reiterated that no one wanted the laboratory to become “a service center for outside organizations — industrial or otherwise.”64 Yet the problem did not go away. An internal MRC report from the following year noted that “the inevitable erosion of academic freedom which results from any commercial exploitation of research findings is a source of resentment by some staff.”65

The collaboration between the MRC and Celltech, in other words, had potential — despite the various challenges and criticism the collaboration faced, no one was urging that it be abandoned — but it had also created the potential for significant professional conflicts of interest, changed the norms of scientific communication and in some cases created resentment among colleagues. In this sense, it was representative of the enormous changes in scientific culture that the commercialization of biotechnology brought to the field of molecular biology during this period.

Where does this leave us? The glossy brochure for the conference Biotech 84 Europe, with its image of DNA backed with the image of a microchip, gives a sense of where the field was in the mid-1980s, after the initial excitement had cooled and the challenges had become apparent. It revealed both the successes of the biotechnology industry as well as pointing to some of the points of tension and conflict. With exhibitions from a wide array of biotech companies and panels on patents, licenses, the international market and “How to Win,” it gives the impression of an industry experiencing rapid growth. Caroline Vaughan, Celltech’s Director of Business Development, gave a presentation entitled “Systems for collaboration in advanced biotechnology” in a panel on “From research into the real world.” Fairtlough was there as well, in a panel on biotechnology and industry. The brochure also included a black and white drawing showing biotechnology specialists in action — thinking, looking through microscopes, conversing, and helming massive computer banks.66 Brenner gave a talk during the plenary session, “Biotechnology — here and now,” entitled “The progress of biotechnology — the promise, potential and reality.” One of the things he addressed was the need to distinguish between scientists and businesspeople: “The roles of the parties should never be confused… Make sure the areas of responsibility are clear and separate.”67 This advice may well have been based on his experience at Celltech.

Celltech wasn’t the only firm that Brenner consulted for. Among others, he also did consulting work for the British firm Biotechnology Investments, Ltd., in the early 1980s and commented half-humorously, half-not about the professional conflicts any indiscretion about this work could cause.68 Brenner’s involvement in the MRC-Celltech collaboration, however, is documented in enough detail to provide a useful picture of how things were on the ground during the biotech boom of the early 1980s. Through his work as a scientist and a biotechnology consultant, he faced the same professional challenges as many of his colleagues in Britain, the United States and elsewhere during this period, as molecular biology transformed from an academic discipline into a thriving industry.

III. Philip Morris

In 1975, the Genetic Engineering Group of Science for the People wrote an open letter to the organizers and participants in the Asilomar conference that compared scientists engaged in recombinant DNA research with tobacco companies. The point of this unflattering comparison was lost on no one.

Twenty years later, in the mid-1990s, Brenner was in negotiations with the Philip Morris company, who were offering to found a molecular biology research institute in the San Diego area with Brenner as its head and endow it with a trust of $225 million, which would provide $15 million a year in funding for fifteen years.69 Although he was excited about having this big new project ahead of him and eager to make connections between the proposed institute and the many other research centers in the San Diego area, Brenner drifted away from the project within a few years, leaving it to a younger colleague, Roger Brent.70 Nevertheless, Brenner’s association with Philip Morris is significant for several reasons.

First, a collaboration between a large corporation like Philip Morris and scientist of Brenner’s stature, who at this stage of his career would have had no trouble obtaining large federal grants through the normal academic funding process, highlighted the continuation of a process that had begun in the 1970s: government funding of basic research was declining, and corporations, whether small biotech startups or large multinationals, were ready to step in and provide lavishly — in exchange for the right to commercialize any marketable discoveries.71

Second, the collaboration called into question the category of “basic research” in molecular biology, which had already been undermined significantly through the changes in the field over the previous twenty years. Did “basic research” mean the pursuit of scientific knowledge purely for its own sake and with no intention to profit commercially? Or could the standards for what counted as “basic” be a little more relaxed? A Philip Morris internal memo written in July of 1994 records a meeting involving the company’s senior scientists which addressed precisely this issue. The scientists in the meeting agreed that the company should fund “basic research,” which was defined as “original investigations that advance scientific knowledge but do not have specific commercial objectives.”72 This left a certain amount of wiggle room, since it was certainly possible to have non-specific commercial objectives. Basic research did not necessarily mean that those doing it or funding it had no plans to use the results for commercial gain.

A brief look at the type of basic research problem Philip Morris intended to fund sheds light on the question of what the potential applicability of this research was and to what extent it was relevant to the corporation’s commercial strategy. They were interested specifically in cell signal transduction, which one science writer termed the “haute biology of the 1990s.”73 Cell signal transduction (or cell signaling) is the process by which molecular signals coming to the cell from the outside are transmitted into the cell’s interior so that it can respond. It is carried out by means of signaling molecules on the surface of and inside the cell. Cell signaling is crucial to the health of the cell, and when this process goes awry, it can cause cells to become cancerous.74 This was a field of great interest to any researcher who wanted to contribute to an understanding of how cells function, which certainly falls under the category of basic research, but its potential applications for a tobacco company are not difficult to guess. Tobacco companies had disputed the link between smoking and cancer for decades. Funding research into cell signal transduction offered both a chance to generate good PR by funding science and, depending on what the research revealed about the causes of cancer, perhaps the opportunity to muddy the waters about the link between cigarettes and lung cancer. (Because Philip Morris had acquired Kraft Foods in the late 1980s, they may also have been thinking about the links between consumption of highly processed foods and a range of health problems, including cancer.) This was flat out denied at the time by Philip Morris, however. A company spokesperson told Science that “This contribution is driven by extremely positive ideals and hopes for the future, not a cynical and negative need to address current controversies.”75

Internally, although the company did not say the word “cancer,” they certainly implied a potential connection. In the July 1994 memorandum that discussed the future molecular biology research institute, it was explained that the research funded by the institute should be of basic scientific significance, and thus allow them to attract top scientific talent, and “perhaps contribute information useful about our products, and thus to the health and enjoyment of our consumers.” Specifically, understanding “signal transduction…will lead to an understanding of the mechanisms involved in both normal as well as aberrant cell growth which results in chronic diseases…More specific to our products, signal transduction is fundamental to understanding the cell mechanisms involved in taste, odor, the impact of nutrition on aging and health, as well as the causes of cellular changes leading to chronic diseases…With control [of these mechanisms] we can affect consumers’ perceptions of our products, as well as improve the effects of those products on the quality of life.”76 If one reads between the lines, the repeated reference to “aberrant cell growth” and “chronic diseases” imply that they were at least aware of the possibility of leveraging the research to change public perceptions about the health risks of their products. Further on in the memo, they stated clearly that “Philip Morris is a company whose products are implicated in human health,” and “our products will be affected and perhaps dramatically changed by developments of basic research.” They wanted to be “ahead of, not behind, these developments.”77 Funding basic research themselves was a way to maintain control over the narrative in terms of the public’s perception of the health risks of Philip Morris products.

In other words, basic research as most scientists understood the term and basic research as Philip Morris understood it were not necessarily the same thing. For the tobacco company, the problems that basic research solved were not theoretical or technical problems in molecular biology — rather, basic research was seen as a way of solving strategic, product development and public relations problems. Just as other aspects of scientific work —collaboration, communication, information-sharing — had changed as a result of the growing commercialization of molecular biology, the Philip Morris example suggests that even the idea of “basic research” had as well.

Finally, the relationship between corporations and scientists on the one hand and “the public” on the other comes up repeatedly. While the organizers and critics of the Asilomar conference in 1975 had grappled with the question of the interaction between scientists and the public, the Philip Morris example highlights a different kind of communication, one that became more and more common as molecular biology became increasingly tied to industry: communication between corporations and the public about science. This communication was not always direct. Often, it came in the form of attempts to manage public perception using science. For example, those at Philip Morris who were involved with the collaboration with Brenner knew that having scientific knowledge at their disposal could help them shape public opinion. The research that they planned to sponsor was to both be and “be seen to be” for the public good. Optics were important. Philip Morris could brighten its public image without the use of conventional advertising, since the new research institute “will be seen as a significant contribution to the public good because of the type of research, the scientists involved…and the quality of its leaders.”78 Both the science and the scientists, including Brenner, were part of the messaging. Along similar lines, the president and chairman of the Scripps Institute, who were also involved in the project, noted that “broad ranging trust by the scientific community and the public” was necessary for this project, and discussed the steps that had been taken to ensure this.79

Tobacco money was contentious. And there were huge sums of it available for those willing to take it — by the 1990s scientists were “increasingly being drawn into the fray” about the ethics of accepting funding from this source. Brenner was not concerned about the potential ethical pitfalls of accepting a significant amount of money from a large tobacco company. Philip Morris emphasized that scientists at the new institute would be free to conduct research as they saw fit, “unconstrained by any obligation to seek out commercially applicable results,”80 and Brenner saw no reason for concern about intellectual freedom. Brenner wasn’t alone in his confidence that such a collaboration could be carried out in a way that maintained intellectual freedom for scientists. Many researchers did see a problem, however. Some had accepted money from tobacco industry organizations such as the Tobacco Research Council and experienced misgivings, either at the time or after the fact. Others felt they had been used by the industry or described situations in which the industry had unfairly criticized individual scientists whose research results they disliked.81 As far as the history of molecular biology is concerned, the significance of the debate about tobacco industry funding is broader than the argument over the ethics of working with tobacco companies specifically. The potential issues that many people would have seen in Brenner’s relationship to Philip Morris was part of a much longer debate over ethics, corporate ties and the funding of molecular biology research. The fear that scientists who accepted funding from large corporations would end up being coopted and lose their intellectual independence had been a recurring theme in the history of the commercialization of molecular biology since the 1970s.

The research that Philip Morris planned to fund at their new institute in the 1990s was not biotechnology in the sense of genetic engineering — they did not express an interest in recombinant DNA methods specifically. At the same time, the focus of the institute was molecular biology research that could be patented and/or used for commercial purposes, which certainly fall into the category of biotechnology broadly defined. Moreover, the issues relating to the practice and ethics of science that arose were very similar to those generated by Brenner’s collaboration with Celltech, for example — ethical conflicts of interest, concerns about intellectual freedom, and the big issue of how science as it was “conventionally” done in universities and pure research institutions could and should operate in this new commercial context.

Conclusion

In 1980, Brenner’s Medical Research Center colleague Christopher Booth asked him what biotechnology was. The answer to this question varies depending on which scientists, or which historians of science, you ask. It is possible to conceive of biotechnology in very broad terms and include a wide variety of inventions and processes that humans have developed over the centuries that involve engineering parts of the natural world to solve problems in food production, industry, and medicine. Alternately, and perhaps more productively, one can focus on the last third of the twentieth century, when a series of scientific discoveries in the field of molecular biology combined with a series of social, political and economic changes to turn “biotechnology” into a buzzword, something that was on the minds of researchers, investors, and the general public.

If we use this latter definition, the development of recombinant DNA technology is central to the story, although it is not the whole story in and of itself. It is true that many of the issues that came up in the context of the scientific advances of the 70s and 80s — things like commercialization of science, patenting, public concerns about potential hazards — had come up before in the context of other scientific discoveries. But the advances made in molecular biology and genetics in those decades allowed researchers (and industry) to do things that really were groundbreaking and occasionally frightening in their implications. Moreover, these discoveries were made in a specific historical context: the economic malaise and energy crisis of the 1970s, the early years of the environmental movement with its distrust of big science, and in the US and UK, the eagerness of the Reagan and Thatcher governments in the 80s to privatize whatever could be privatized, deregulate whatever could be deregulated and spur economic growth at all costs. It was the combination of scientific discovery and a specific societal context that turned biotechnology into a buzzword for investors, a source of excitement and occasionally frustration and stress for scientists, and a line item in public opinion polls.

Sydney Brenner’s career spanned this period, and the Brenner collection contains notes, correspondence, memoranda and many other documents that illuminate key themes and events of the biotechnology boom — there is a vast amount of material there for exploration of the big themes and questions of the history of modern biotechnology.

References

1 C. C. Booth to Sydney Brenner, 13 March, 1980. SB 1/2/5 (Sydney Brenner Collection, Series 1 (Correspondence), Sub-series 2 (Institutional), Box 5), Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988.
2 Daniel T. Kevles, “Ananda Chakrabarty wins a patent: biotechnology, law and society, 1972-1980,” Historical Studies in the Physical and Biological Sciences 25, 1 (1994): 111-135.
3 Soraya de Chadarevian, “The making of an entrepreneurial science: biotechnology in Britain, 1975-1995,” Isis 102, 4 (Dec. 2011): 601-633.
4 For an account that stresses the longue durée of biotechnology and the breadth of techniques and applications, see Robert Bud, The uses of life: a history of biotechnology (Cambridge: Cambridge University Press, 1993). For an in-depth analysis of the “recombinant DNA revolution,” see Susan Wright, “Recombinant DNA technology and its social transformations, 1972-1982,” Osiris 2 (1986): 303-360, “Molecular biology or molecular politics? The production of scientific consensus on the hazards of recombinant DNA technology, Social Studies of Science 16, 4 (Nov. 1986): 593-620 and Molecular Politics: Developing American and British Regulatory Policy for Genetic Engineering, 1972-1982 (Chicago: University of Chicago Press, 1994). Scholars such as Lily E. Kay and Angela Creager have emphasized that many of the aspects of the “recombinant DNA revolution” in the 1970s are not as new as they might appear, suggesting that “revolution” is far too strong a word. See Lily E. Kay, “Problematizing basic research in molecular biology,” and Angela Creager, “Biotechnology and blood: Edwin Cohn’s plasma fractionation project, 1940-1953,” both in Arnold Thackeray, ed., Private science: biotechnology and the rise of the molecular sciences (Philadelphia: University of Pennsylvania Press, 1998), pp. 20-38 and 39-62.
5 Bud, Uses of Life, 141-152.
6 Susan Wright, “Recombinant DNA technology and its social transformation,” 309-311.
7 Bud, Uses of Life, 167-171.
8 Chadarevian, “The making of an entrepreneurial science,” 601.
9 Sally Smith Hughes, “Making Dollars out of DNA: The First Major Patent in Biotechnology and the Commercialization of Molecular Biology, 1974-1980,” Isis 92, 3 (September 2001): 541-575, quote p. 543.
10 Kevles, “Ananda Chakrabarty wins a patent,” 135.
11 Bud, Uses of Life, 141-149.
12 Bud, Uses of Life, 154.
13 Hughes, “Making dollars out of DNA,” 570-571.
14 Nathan Crowe, “The historiography of biotechnology,” in Michael Dietrich, Mark E. Borrello and Oren Harman, eds., Handbook of the Historiography of Biology (Springer Reference, 2021), 217-242, pp. 233-234.
15 Hughes, “Making dollars out of DNA,” 542, 544; Errol C. Friedberg, Sydney Brenner: a biography (Cold Spring Harbor: Cold Spring Harbor Press, 2010), 181-183.
16 Doogab Yi, “Cancer, viruses and mass migration: Paul Berg’s venture into eukaryotic biology and the advent of recombinant DNA research and technology, 1967-1980, Journal of the History of Biology 41, 4 (Winter 2008): 589-636.
17 Friedberg, Sydney Brenner, 182-184.
18 Paul Berg et al., “Potential biohazards of recombinant DNA molecules,” Science 185, no. 4148 (July 26, 1974): 303.
19 Friedberg, Sydney Brenner, 184-185, quote from Brenner’s white paper p. 185.
20 Friedberg, Sydney Brenner, 185.
21 Paul Berg to Sydney Brenner, September 17, 1974, SB 1/2/43.
22 Priska Gisler and Monika Kurath, “Paradise lost? ‘Science’ and ‘the public’ after Asilomar,” Science, Technology & Human Values 36, 2 (March 2011): 213-243.
23 Paul Berg to Sydney Brenner, March 15, 1975, SB 4/1/2 (Sydney Brenner Series 4 (Subject files), Sub-series 1 (General), Box 2), Folder: Asilomar meeting on biohazards, Jan-March.
24 Genetic Engineering Group of Science for the People, Open letter to the Asilomar Conference on Hazards of Recombinant DNA, SB 4/1/2, Folder: Asilomar meeting on biohazards, Jan-March.
25 Genetic Engineering Group of Science for the People, Open letter to the Asilomar Conference on Hazards of Recombinant DNA, SB 4/1/2, Folder: Asilomar meeting on biohazards, Jan-March.
26 Friedberg, Sydney Brenner, 187-188, quote from Brenner on p. 188.
27 Paul Berg, David Baltimore, Sydney Brenner, Richard O. Roblin and Maxine Singer, “Asilomar conference on recombinant DNA molecules,” Science 188, no. 4192 (June 76, 1975): 991-994; Paul Berg, David Baltimore, Sydney Brenner, Richard O. Roblin and Maxine Singer, “Summary statement of the Asilomar conference on recombinant DNA molecules,” Proceedings of the National Academy of Sciences of the United States of America, 72, 6 (June 1975): 1981-1984.
28 Susan Wright, “Molecular biology or molecular politics?”, 598.
29 Geisler and Kurath, “Paradise lost?” 215.
30 Unnamed immunologist, quoted in Geisler and Kurath, “Paradise lost?”, 228.
31 Marcia Barinaga, “Asilomar revisited: lessons for today?” Science 287, no. 5458 (March 3, 2000): 1584-1585.
32 Marcia Barinaga, “Asilomar revisited,” 1584.
33 Sydney Brenner, Lewis Wolport, Errol C. Friedberg and Eleanor Lawrence, Sydney Brenner: A life in Science (London: Science Archive Limited, BioMed Central Limited, 2001), 157.
34 Marcia Barinaga, “Asilomar revisited,” 1584.
35 Paul Berg to Brenner, September 17, 1974, SB 1/2/43.
36 Geisler and Kurath, “Paradise lost?” 229-230.
37 Sheldon Krimksy, Genetic alchemy: the social history of the recombinant DNA controversy (Cambridge, MA: MIT Press, 1982), 68.
38 Tony Vickers to C. C. [Chris] Booth, 17 March 1980. SB 1/2/5, Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988.
39 Susan Wright, “Recombinant DNA technology and its social transformation,” 328.
40 Hughes, “Making Dollars of DNA,” 569.
41 “How to make a Nobel Prize Pay,” Financial Times, May 13, 1983, in SB 4/1/5, Folder: Celltech, 1981-1984; and “Biotechnology” NEB press release, 23 July 1980, SB 1/2/5, Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988.
42 Third draft of agreement between Celltech, the MRC and the NEB, page 2 and Schedule 1, SB 1/2/5, Folder: Celltech-MRC agreement.
43 David Fishlock, “How to make a Nobel Prize Pay,” Financial Times, May 13, 1983, in SB 4/1/5, Folder: Celltech, 1981-1984
44 “One way ahead for British biotechnology,” Nature 285 (5 June 1980): 349. SB 1/2/5, Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988.
45 Brenner to Vickers, 20 February 1980, SB 1/2/5, Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988
46 Celltech NRDC, Comments on proposed agreement between Celltech and NRDC, plus Brenner’s notes, SB 1/2/5, Folder: Celltech – MRC Agreement, National Enterprise Board, 1979-1980; 1988.
47 Watson to G. H. Fairtlough, 17 September 1980, Zinder collection, Box 130, cited in Wargas and Pollock, “Second Century: Cold Spring Harbor Laboratory and the Biotechnology Revolution,” page 8.
48 Sydney Brenner to Charles Kirkman, 11 June 1981, SB 1/2/5, Folder: Celltech, 1981.
49 Second review of progress in implementing the MRC/Celltech agreement, 5 November 1981. SB 4/1/5, Folder: Celltech, 1981-1984.
50 Cesar Milstein, memo to Sydney Brenner, 21 April, 1981. SB 1/2/26, Folder: MRC—Celltech. Italics in original.
51 Untitled memo by Brenner, 29 April 1981, in SB 1/2/26, Folder: MRC-Celltech.
52 Kirkman to Ron Cox (Celltech), 8 September 1981. SB 1/2/5, Folder: Celltech, 1981.
53 Memo by SB dated 27 July, 1981. SB 1/2/5, Folder: Celltech, 1981. Italics in original.
54 Biotechnology: Report of a Joint Working Party (London: 1980), Sydney Brenner Collection, pp. 26-27,
55 Memo by SB dated 27 July, 1981. SB 1/2/5, Folder: Celltech, 1981.
56 William [Bill] Matthews to Sydney Brenner, 2 February 1983, and “Review of MRC/Celltech Agreement, Working Document,” SB 4/1/5, Folder: Celltech—Policy, 1982-83.
57 Brenner, handwritten note dated 12 June [1981], C. A. Kirkman to Brenner, 3 June 1981, and Fairtlough to Brenner, 29 May 1981 with enclosed draft, SB 1/2/6, Folder: Celltech — immunoassay project.
58 Draft Statement: Changes in membership to the Celltech Science Council, 17 November, 1981, SB 1/2/6, Folder: Celltech — Science Council, 1980-1981.
59 Charles Kirkman to Sydney Brenner, 28 September 1981, SB 1/2/5, Folder: Celltech — Fairtlough, Gerard 1981-1987.
60 “Minutes of Meeting of Science Council held on Tuesday, 24 November, 1981,” SB 4/1/5, Folder: Celltech, 1981-1984.
61 “Minutes of Meeting of Science Council held on Tuesday, 24 November, 1981,” and “Second review of progress in implementing the MRC/Celltech agreement, 5 November 1981,” in SB 4/1/5, Folder: Celltech, 1981-1984.
62 “Second review of progress in implementing the MRC/Celltech agreement, 5 November 1981,” in SB 4/1/5, Folder: Celltech, 1981-1984; Kirkman to Fairtlough, 12 November 1981, in Sydney Brenner 1/2/6, Folder: Celltech – science council 1980-1981.
63 Sydney Brenner, memo “To all members of the scientific staff,” 30 October, 1981, in SB 1/2/5, Folder: Celltech — Fairtlough, Gerard 1981-1987.
64 Sydney Brenner, memo “To members of the scientific staff,” 13 November 1981, in SB 1/2/25, Folder: MRC—Celltech.
65 Medical Research Council, “Commercial Exploitation” report, 82/ST117, July 1982, Annex 1: “Research and marketing agreement with Celltech Limited — progress report,” page 2. SB 4/1/5, Folder: Celltech — Commercial Exploitation, 1982.
66 Biotech 84 Europe: International Conference & Exhibition brochure, SB 1/2/3, Folder: Biotech 84 Europe, 1984.
67 Sheet of paper with info on the plenary session, and green conference flier about the plenary session, SB 1/2/3, Folder: Folder: Biotech 84 Europe, 1984.
68 SB to David Leathers, 9 February, 1984, SB 1/2/3, Folder: BIL — Brenner wishes that his name not be used in the BIL prospectus, 1984; see also SB 1/2/3 Folder: BIL (Biotechnology Investments, Ltd), 1981, 1983 and SB 4/1/3, Folder: Biotechnology Investments Ltd.
69 Draft proposal for the creation of the Philip Morris Institute for Molecular Science,” SB 1/2/32, Folder: Philip Morris, 1994, p. 10.
70 Jon Cohen, “Tobacco money lights up a debate,” Science 272, no. 5261 (April 26, 1996): 488-494, 489; Friedberg, Sydney Brenner, 256.
71 Cohen, “Tobacco money,” 490-491.
72 Memorandum re: Research Institute, SB 1/2/32, Folder: Philip Morris, 1994. Italics in original.
73 Cohen, “Tobacco money,” 489.
74 NIH, National Cancer Institute, NCI Dictionary, “Signal transduction,” via https://www.cancer.gov/publications/dictionaries/cancer-terms/def/signal-transduction, accessed 5/26/21.
75 Statement by Philip Morris spokesman George Knox, quoted in Cohen, “Tobacco money,” 489.
76 Memorandum re: Research Institute, SB 1/2/32, Folder: Philip Morris, 1994, pages 2-3.
77 Memorandum re: Research Institute, SB 1/2/32, Folder: Philip Morris, 1994, page 7.
78 Memorandum re: Research Institute, SB 1/2/32, Folder: Philip Morris, 1994, page 3.
79 Gerald Edelman and Richard Lerner to Charles Wall, 30 June, 1994, SB 1/2/32, Folder: Philip Morris, 1994, pp. 3-4.
80 Draft proposal for the creation of the Philip Morris Institute for Molecular Science,” SB 1/2/32, Folder: Philip Morris, 1994, page 15.
81 Cohen, “Tobacco money,” 489-491.

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