The People vs. Recombinant DNA
The ragged coalition against genetic engineering
Welcome (back) to The Science Fictional Now! After an incredibly hectic summer, I’m finally back with another essay - one that I think will have been worth the wait. Those of you who read my first post on the Enhanced Games will know that I’m fascinated by the numerous ethical debates prompted by advances in synthetic biology; today’s post covers a specific historical instance when such arguments spiraled into a full-on political controversy.
The recombinant DNA debates captivated the nation during the 1970s and while the new technology they centered on would spark the biotech revolution, the debates themselves have also had a lasting impact. Arguments laid out during the controversy have repeatedly resurfaced in opposition to newer biologies, impacting both public opinion and regulations. If we want similar debates in the future to be nuanced and productive, we need to first look to the past.
The People vs. Recombinant DNA
As protestors descended on Washington, D.C. for the National Academies’ 1977 Research With Recombinant DNA forum, Roger Noll decided he had to get something off his chest. Noll, a Caltech economist who had consulted for the Los Angeles Lakers, announced that he had a conflict of interest: the team would “like to clone Wilt Chamberlain.”
Noll’s humorous admission marked a moment of levity in an otherwise contentious environment, which was the product of controversial new bioengineering techniques making their way into the public sphere. Scientists’ capacity to engineer living organisms has only increased in the 50 years since the recombinant DNA (rDNA) controversy began, and understanding its origins is crucial for dealing with the protests that will likely accompany the development of new biotech, with all of its ethical dilemmas, going forward. The story of rDNA is one of transformative achievements in molecular biology, but also one of social crisis and the emergence of a heterogeneous group opposing rDNA fractured existing coalitions.
To understand this conflict, let’s first take a step back in order to understand the seminal experiments that led to the creation of the technology. After exploring the origins of rDNA, we’ll trace the technology’s path into the public sphere and the spirited discussions of biosafety and bioethics that this inspired. Finally, we’ll discuss the establishment of scientific consensus that ended the rDNA controversy and set the stage for subsequent public debates about bioethics.
The beginning
It’s easy to take for granted the ease with which modern molecular biologists can read, write, copy, and paste DNA sequences. The cost of sequencing a human genome has fallen nearly five orders of magnitude over the past two decades, and designer sequences can now be synthesized base-by-base. Scientists can easily express nearly any gene of interest in fast-growing E. coli using a process called “molecular cloning” (or simply “cloning”), which involves inserting the desired DNA sequence into a circular vector called a plasmid that can then be transformed into bacteria.
Modern-day cloning traces its origins to techniques developed in the early 1970s, when researchers first devised ways to move fragments of DNA between organisms. Such hybrid sequences became known as “recombinant DNA” and their construction quickly became a technique of interest for researchers across molecular biology. The ease of genetic manipulation that rDNA techniques allowed were a boon to those doing basic research and would play a crucial role in the emergence of the modern biotechnology industry later in the ‘70s.
Of course, the story of rDNA involves far more than just experiments done in molecular biology labs. In 1978, Harvard biochemist Wally Gilbert made the decision to send part of his research group - which was locked in a race to produce human insulin using r DNA - to England, fearing that the hostile environment at home in Cambridge was hampering their efforts. Gilbert’s team inhabited the same Harvard where “young protestors were carrying placards against gene cloning1” in the aftermath of contentious public hearings over the previous two years. The notion of student protests brings to mind images of the long-haired youth who had challenged the Vietnam War in the 1960s; it’s perhaps less obvious why college students a decade later would be protesting advances in molecular biology.
The political activism of the ‘60s did lay some of the groundwork for protests against rDNA, but socially-minded scientists ultimately came down on both sides of the issue. Biologists’ newfound ability to manipulate living organisms prompted questions about the other forms of power they wielded, and rDNA opponents frequently drew on frameworks established in the ‘60s to criticize scientists' regulatory influence and growing financial incentives. At the same time, however, the scientific legitimacy of rDNA research was challenged by older biologists and others raised questions about rDNA’s the philosophical implications. The protests against rDNA were symptoms of both the lingering influence of the ‘60s and broader scientific and societal trends of the ‘70s.
Recombinant DNA origins
In the 1960s, Stanford biochemist Paul Berg became fascinated with the idea of introducing foreign genes into animal cells to study mechanisms of gene regulation. Berg wondered if he could accomplish this by creating hybrids of eukaryotic and bacterial viruses that could both infect mammalian cells and introduce DNA into their host cell’s genome.
Berg’s group demonstrated the creation of such hybrids in 1972, adding genes from the canonical bacteriophage lambda into the genome of the monkey virus SV40 using restriction enzymes, i.e., proteins that cut DNA at a specific sequence. By cutting the two circular DNA sources using the same enzyme, they could generate linear DNA molecules with matching sequences at their ends; these could then be annealed together to generate recombinant viruses. This work had already drawn the attention of other scientists, who worried that introducing these recombinant viruses into E. coli might allow them to be transmitted to humans via the gut microbiome. Berg was ultimately persuaded not to proceed with rDNA experiments in large part because SV40 was known to cause cancer in humans.
The restriction enzyme cloning method that Berg’s lab had used to create their recombinant SV40 had been developed in the lab of his Stanford colleague Stanley Cohen. Collaborating with Herbert Boyer’s lab at the University of California, San Francisco, Cohen’s group created the first recombinant bacterial plasmids in 1973. The plasmids generated in the study retained the characteristics of their natural precursors: the small, circular DNA molecules could be transformed into bacteria and replicated along with their bacterial hosts. While improvements have been made to the original method, the use of recombinant plasmids remains the dominant paradigm in molecular cloning today.
Researchers quickly took to cloning genes of interest into plasmid vectors that could be expressed in fast-growing E. coli. Typically, they used the lab strain K-12, which was known not to be pathogenic or even particularly robust outside of a test tube. Some scientists, however, raised further safety concerns: could the expression of new genes in E. coli produce toxins, increase pathogenicity, or give the bacteria new qualities? The specifics of how rDNA research proved important in shaping the discourse on the subject, and safety concerns became both the first and most enduring criticisms of the emerging field.
These worries gained traction within the scientific community when a group led by Berg himself proposed a moratorium on certain rDNA experiments in 1974. Since stopping his experiments in 1971, Berg had gathered perspectives from more of his colleagues at scientific conferences. A meeting on the topic was held in Asilomar, California in 1973, and similar debates took center stage at the Gordon Conference on Nucleic Acids held the same year. Berg gathered a group of specially-selected scientists and penned an op-ed in Science calling for a pause on experiments involving the cloning of toxin and antibiotic resistance genes, as well as any DNA animal viruses.
Although this voluntary self-regulation was ostensibly driven by safety concerns, it faced criticism from European biologists, who saw it as a tactic for American rDNA pioneers to maintain their competitive edge. One “Berg letter” signatory, Rockefeller University biologist Norton Zinder, later wrote that researchers across the pond felt some of the authors had already violated the letter’s spirit, indicating that Americans might turn a blind eye to future infractions.
Berg and colleagues gathered in early 1975 for a second, more famous conference at Asilomar to establish consensus on rDNA experiments. Despite the presence of some lawyers and ethicists at the conference, its attendees were primarily scientists. Berg and MIT virologist David Baltimore were particularly noted for their outsized influence; Baltimore’s influence grew even further when he was awarded the Nobel Prize in Physiology or Medicine later that year. Berg and Baltimore penned the conference’s summary statement with fellow scientists Sydney Brenner, Richard Roblin, and Maxine Singer.
Scientists at the conference worried2 that external regulation represented an existential threat to their freedom of inquiry, and discussed how best to preserve this freedom going forward. Thus, while the participants did ultimately decide to delay certain experiments, such precautions were characterized by some as methods to stave off more stringent external regulation. Lawyer Alexander Capron, who participated in the conference, argued that “while science has freedom of enquiry if thinking is all that is involved, when doing and acting is involved there's no special privilege for scientific actions.” Questions about free inquiry, risk management, and who should control the types of experiments that were permitted would arise again as the rDNA debates intensified. After Asilomar, scientists promptly resumed experiments under the guidelines put forth by the conference.
Beginnings of the Cambridge controversy
The Asilomar statement set the stage for a new list of guidelines in 1976 from the National Institutes of Health, where Maxine Singer was the chief of Nucleic Acid Enzymology. rDNA research flourished in the wake of the conference and Herbert Boyer co-founded Genentech, marking rDNA’s entrance into the industrial sphere; the company would help create the modern biotech industry and grow into a corporate juggernaut. Universities looked to support the expansion of rDNA research, and Harvard proposed the construction of a new heightened biosafety lab to conduct experiments that fell under the “P3” category of the NIH guidelines3.
Initial discussions of the facility took place at meetings primarily attended by Harvard faculty and Wally Gilbert noted that many of the arguments seized on by rDNA critics were raised in this venue. Cambridge City Councilwoman Barbara Ackerman attended one of these early meetings at the behest of biology professor Ruth Hubbard, a friend from the peace movement. Ackerman also cited the 1971 film adaptation of Michael Chrichton’s The Andromeda Strain as part of her motivation for attending and similar fears of contagion would continue to be deployed against rDNA.
Reporters from the Boston Phoenix had also attended the meeting and published a cover story titled “Biohazards at Harvard” soon after. Hubbard’s husband George Wald, a Nobel Laureate biochemist already known for his apocalyptic predictions and anti-War activism, protested directly to Cambridge’s Mayor Alfred Vellucci. Wald’s plea coupled with the rising public animosity led Vellucci to take action. Jumping at the chance to regulate Harvard, he quickly set a council meeting for June 23rd.
By 1976, Vellucci had gained notoriety as a hard-nosed politician with little tolerance for the universities synonymous with Cambridge. Vellucci disdained Vietnam protestors and intellectuals alike, making his newfound alliance with Wald an unconventional one. Vellucci quickly became suspicious of Harvard’s proposed P3 facility, worrying that scientists might create new diseases or even Frankenstein-style monsters. While it’s unusual for municipal governments to participate in scientific governance, Vellucci clearly appreciated the power he had as the mayor of a city housing two elite research universities.
A few scientists wrote letters to Vellucci in the days leading up to the meeting encouraging restriction of rDNA research. One Mr. Long4 of Cambridge Hospital cautioned Vellucci not to vilify Harvard scientists a priori but urged caution given the number of unknowns in rDNA research. Other correspondence echoed similar concerns, and the resistance to rDNA in Cambridge increasingly focused on public health and worker safety.
Also in Vellucci’s inbox was a short letter from Erwin Chargaff, the retired Columbia University biochemist known for his eponymous “rules” describing biochemical characteristics of DNA. Chargaff had published an op-ed in Science thoroughly critiquing rDNA research in the same month, and he urged Vellucci to consider not only the safety risks of the research, but also what he saw as a lack of scientifically and ethically rigorous thinking.
Chargaff’s scientific critique of rDNA research was vaguely worded but stinging nonetheless; he called most rDNA experiments “unimpressive” and dismissed the whole field as “second-rate molecular biology.” Chargaff opined that hosts safer than E. coli could have been chosen, but also that this paled in comparison to the transgressive act of creating organisms not found in nature. He wrote that “What seems to have been disregarded completely is that we are dealing here much more with an ethical problem than with one in public health” and warned that engineered microbes could constitute “an irreversible attack on the biosphere.”
Chargaff had already become a critic of molecular biology by the 1950s, which he called “biochemistry without a license”; he believed strongly in the complexity of nature and regarded it as something to be studied, not manipulated. These persuasions led him to become a prominent critic of other advances in biotechnology, mostly notably in vitro fertilization. Chargaff was perhaps one of the more extreme critics of recombinant DNA, but the nature of his objections and his condescending insistence that rDNA researchers “study hard” nonetheless illustrated the generational gap between scientists that had emerged. The proliferation of engineering-based approaches was antithetical to the purely discovery-oriented view of biology held by Chargaff and other members of the field’s “old guard.” This difference in philosophy led them to question the very scientific legitimacy of rDNA research.
Indeed, scientists in the ‘70s were divided not only by their attitudes towards science but also towards political and cultural issues. Geneticist Arnold Levine noted that many new professors in the ‘60s and ‘70s had different research philosophies than their older colleagues, but also that these younger researchers “liked Bob Dylan and rock music and hated the Vietnam war, rebelling against their countries’ decisions.” Unsurprisingly, conflicts arose when these same elements of ‘60s counterculture were mobilized in opposition to rDNA research.
One such critic was MIT biologist Jonathan King, who sent a short letter to Vellucci simply asking for a chance to speak at the council meeting. Inspired by Nobel-winning chemist Linus Pauling’s anti-nuclear activism, King became involved in anti-war protests as a student and helped organize the 1969 scientists’ strike against the Vietnam War as a young faculty member at MIT. David Baltimore had also been involved in the strike but now found himself at odds with King over rDNA; the ideological camps formed among socially-minded scientists in the ‘60s were beginning to fall apart.
King was associated with the advocacy organization Science for the People (SftP), a group known for their distinctly anti-capitalist critique of modern science. SftP’s suspicion of rDNA arose from its role in commercializing molecular biology, and the group warned that the field was subject to profit and career incentives that came at the expense of social good. The group questioned the validity of self-regulation and worried that dangerous research would put both experimentalists and the general public at risk. SftP was based in Cambridge and boasted the membership of both current students and older activists like King who had cut their teeth in the protests of the ‘60s. The group remained a key rDNA opponent throughout the Cambridge controversy and as the discussion went national.
The hearings
Vellucci kicked off the June 23rd City Council meeting in characteristic fashion, warning speakers not to “use the alphabet”. To the cynical observer, the mayor seemed intent on sticking it to the university intellectuals that he so clearly despised, while more sympathetic attendees saw him as a defender of the common people. Harvard molecular biologist Mark Ptashne and the NIH’s Maxine Singer spoke in favor of rDNA, assuring Cambridge residents that rDNA experiments were not inherently risky and that the P3 facility would contain any unforeseen hazards. Ptashne also emphasized that he saw this as a consensus view, stating that the vast majority of biologists supported rDNA research and thought it was safe.
Ptashne and Singer were subjected to intense questioning by Vellucci and other Councilmembers, who seemed uncomfortable with both the fact that the NIH guidelines had been so heavily influenced by scientists and the level of technical knowledge necessary to understand them. Risk estimation was another sticking point, with Vellucci demanding an assurance of zero risk and the scientists stating that this was impossible to give; there are no absolutes in biology.
While Ackerman observed that the students in attendance were heavily in favor of rDNA, the crowd as a whole seemed to favor regulation: many brought anti-rDNA signs with them and emphatic points against the technology were met with hearty applause. By the 1970s, disillusionment and distrust of institutions had spread from the heart of the radical movement to mainstream society. The controversial, recently-abolished Atomic Energy Committee had brought scientific organizations under fire and the 1974 Watergate Scandal had brought American trust in the government to a nadir. Cambridge citizens were primed not to trust what authority figures told them, including the scientists and government officials who had told them that rDNA experiments were safe.
Jonathan King had the chance to speak as he’d requested and delivered a rousing speech questioning the rigor of the NIH guidelines and offering examples of potential harms from rDNA experiments; he would continue to speak on the latter topic in lectures and at scientific conferences. King also challenged Ptashne’s assertion that the scientific community supported rDNA research, instead asserting that most researchers harbored serious safety concerns.
Ruth Hubbard also spoke against allowing rDNA research, alleging that the proposed facility wouldn’t be able to contain pathogens that might arise. She argued that “unknowns” surrounding rDNA would need to be studied in isolated containment labs before researchers in populated areas could be allowed to conduct the experiments being proposed. While Hubbard had been involved in the peace movement just like King, she was an older, more experienced researcher and her objections to rDNA research derived from her scientific philosophy in addition to her concerns about safety. She was still nearly 20 years Chargaff’s junior, but her views on scientific knowledge matched his more closely than those of her colleagues in the “Bob Dylan generation.”
Like Chargaff, Hubbard was invested in the idea that biological phenomena were highly complex and resented the notion of programmability that rDNA offered. She referred to the renewed focus on genetics kicked off by the discovery of the structure of DNA as “genomania” and saw it as a reductionist manner of scientific thinking. Hubbard also worried about the social consequences of this logic: her family had fled Austria in 1938 and she saw uncomfortable parallels between the new biology and the Nazi eugenics that she had escaped.
Despite the fact that the rDNA debate had graduated to public forums, well-known scientists who derived their credibility from reputations built on research done at prominent universities remained the most influential speakers on both sides of the issue5. Paradoxically, a controversy centered on public health concerns was repeatedly buoyed not by private citizens, but by the voices of influential scientists; Nobel Laureates like Wald and Baltimore were difficult to ignore.
Interregnum and decision
The contentious June 23rd meeting was followed by a two-week “cooling off” period and second meeting, where Vellucci announced the verdict. The Mayor formed a citizens’ review board to review the NIH guidelines and instituted a three-month ban on P3-level rDNA experiments. During the interregnum, Vellucci was eager to press his advantage and arrived at the United States Conference of Mayors with a sample resolution requiring any universities planning to conduct rDNA research to notify their city’s mayor first. He also sponsored “pro-con booths” in Cambridge’s Kendall Square, which pitted Harvard and MIT researchers against SftP members, to “educate the man on the street.”
Letters had flowed into city hall since the first council meeting, with various parties expressing support for the moratorium or imploring Vellucci to back off. A number of prominent scientists wrote in favor of allowing the research, including Paul Berg and James Watson (of The Double Helix fame). Some of these researchers mentioned that they had been asked to write by Ptashne6, who likely sought to provide evidence of the scientific consensus he had mentioned during his testimony and recruit some Wald-level firepower of his own in the process. Some of these letters stuck to general statements about the safety and potential benefits of rDNA research while others added more flair. Berg called for a “partnership for progress rather than a conspiracy of repression” while Nobel-winning biochemist Severo Ochoa spoke of the potentially transformative benefits of rDNA research, including synthetic insulin and cures for debilitating genetic diseases.
These letters were accompanied by an increasing number from lay residents of Cambridge, most of whom felt that a moratorium was justified. Another short communique from the environmental group Friends of the Earth (FoE) simply stated “We strongly support your position against any laboratory for recombinant DNA research at Harvard.”
FoE was founded during the same period of environmental activism that led to the first Earth Day in 1970 and was therefore ideologically linked to the peace movement. Environmental groups became major opponents of rDNA research as the controversy rose in profile throughout 1976, invoking naturalistic thinking that had long been the basis of conservation efforts. Like SftP, these groups were suspicious of the commercial potential that rDNA offered, seeing it as being at odds with environmental protection. Worried that rDNA research might impact the environment in unexpected ways, attempted to stop federal funding of rDNA research via a 1977 lawsuit focusing on the lack of an environmental impact statement in the NIH guidelines.
Environmental organizations’ entrance into the rDNA debates fractured coalitions that had developed a decade earlier, as scientists affiliated with the environmental groups pushed them to change their stances on rDNA. Stanford biologist Paul Ehrlich tried in vain to convince FoE to reverse their opposition to recombinant DNA and Lewis Thomas, then the president of Memorial Sloan Kettering Cancer Center, resigned from the organization’s advisory board in the wake of their 1977 lawsuit.
Vellucci’s three-month ban was lengthened to six as the citizens’ review board continued its deliberations, but in January of 1977 the group delivered its final report, which found the NIH guidelines to be generally quite sound. The group called only for two additional provisions, which allowed the City of Cambridge to maintain a degree of municipal oversight. A local biosafety board was established and the intent to conduct epidemiological studies of researchers working with rDNA was announced.
By this time, Vellucci had established himself as one of the foremost advocates of rDNA regulation and continued to discuss the topic on radio and TV programs. These appearances earned him even more letters, including from outside of Cambridge. A high school principal from Alberta, Canada expressed concern with rDNA research, and a clinical psychologist from Los Angeles enclosed the report of a review committee in San Diego, which took a more critical view of the NIH guidelines. Another letter came from a Salt Lake City preacher named Pilcher Godwin who supplied religious objections to rDNA research.
While Wally Gilbert mentioned encountering faith-based objections to rDNA research, religious organizations were surprisingly quiet on the subject. Prominent Christian theologians had discussed the ethics of theoretical human cloning scenarios since the mid-60’s, but the specifics of the rDNA controversy remained strangely absent from such conversations. Even a 1977 pamphlet titled “Genetic Manipulation” published by the United Church of Christ provided only a basic overview of the science, stopping short of issuing any moral pronouncements.
Science and religion have long come into conflict, and Pilcher Godwin’s opposition to rDNA research was clearly rooted in a belief that the two were often irreconcilable, illustrated by his observation that the word “scientists” contains the letters to spell “sin.” Pilcher’s opposition stemmed from a belief that bioengineers were “playing God,” which has since become a common religious objection to genome editing.
Some bioethicists reached similar conclusions based on secular philosophy: Leon Kass expressed such an intrinsic value of naturality in his 1971 essay “The New Biology: What Price Relieving Man’s Estate?” While Kass was likewise more concerned with the potential manipulation of human genomes than the recombinant microbes that had already been created, he viewed the two as symptoms of the same type of hubris. In this regard, Kass’ argument resembles those made by Chargaff and Hubbard when they extolled the unknowable complexity of natural life.
Most Cambridge residents, however, remained fixated on safety, and a group called the Safety for Cambridge Residents Committee sent Vellucci a letter expressing a “consensus viewpoint” opposing rDNA research. The group admitted there was not much to be done in light of the review board’s report but assured Vellucci that “at the next election our support for your actions will be most apparent.” For his part, the mayor sent a letter to the president of the National Academies implying that recently reported monster sightings in the Boston area might be connected to rDNA research.
The National Academies forum
Cambridge was just one of several geographic loci where rDNA research had become a subject of scrutiny, but the amount of publicity it generated played a key role in elevating the rDNA controversy into a truly national affair. The debate finally made its way to Washington in 1977, when the National Academies hosted a forum on rDNA research.
Even before it began, the forum drew criticism from rDNA regulation proponents. SftP criticized the forum for its lack of impartiality, since the event was sponsored by a number of pharmaceutical and biotech companies. George Wald and the newly-formed Coalition for Responsible Genetic Research called for a nationwide moratorium on any research that produced combinations of genes not found in nature. The Nobel Laureate upped the ante even further when he dubbed rDNA “perhaps the biggest issue in the history of science and said that the experiments might constitute the biggest break with nature.”
Like Ptashne and Singer in Cambridge, the scientists who spoke in favor of rDNA research at the forum weren’t in for an easy ride. Vellucci had been worried about Frankenstein, but rDNA opponents in Washington brought objections more inspired by Brave New World. One group of protestors brought a sign emblazoned with a Hitler quote about creating a master race, channeling the same Huxleyan fears that Kass had articulated in his 1971 essay. A group called the People’s Bicentennial Commission (PBC) staged a more vocal interruption, chanting “We Shall Not Be Cloned” while marching around the auditorium holding protest signs. Social theorist Jeremy Rifkin, who had founded the PBC several years earlier, echoed SftP’s criticism of the forum, describing it as a closed event rigged by pharma companies and scientists who stood to benefit financially from rDNA.
Rifkin was another young activist who had cut his teeth in the student protests of the ‘60s and had formed the PBC’s ethos by viewing what he learned there through an economic lens. Rifkin’s continued dedication to “revolutionary alternatives” was predicated on the belief that economic change was central to achieving social good. Rifkin published a book critiquing the emerging biotech industry later in 1977, and while his philosophical objections to rDNA resembled those of Wald, Hubbard, Kass, and others, he was also acutely attuned to the power dynamics at play. Where others might have wondered if “man should play God”, Rifkin’s volume was titled “Who Should Play God?” (italics my own). The PBC called for all speakers at the forum to disclose conflicts of interest but outside of Roger Noll’s tongue-in-cheek Wilt Chamberlain joke, few academics mentioned any commercial ties.
In spite of such efforts however, the forum once again focused primarily on biosafety and public health concerns. For example, union director Anthony Mazzocchi opposed rDNA research during the forum because he feared it would endanger technical workers, but believed that research could proceed once the “facts [were] out in the open.” Wald lamented that “The broad questions have not really been addressed. We turn with relief to problems of safety because they are easier.”
Ultimately, the forum ended up simply rehashing previous rDNA debates and consensus seemed no closer than before the meeting. Journalist E.M. Leeper called it the “scientific show of the year.”
The birth of consensus
Despite this residual uncertainty, development of a scientific consensus on the safety of rDNA research was already underway. Historian of science Susan Wright, who was herself involved in the rDNA debates at the University of Michigan, has detailed how a set of key scientific conferences helped form this consensus and quell the raging controversy. At the 1976 Enteric Bacteria Conference, researchers began to recognize that answering questions about the safety of rDNA research represented the best way to avoid regulation that could permanently curtail their freedom of inquiry.
The 1977 Falmouth Conference was accordingly dedicated to identifying potential risks of rDNA research and devising experiments to test them empirically. While the meeting wasn’t completely conclusive in itself, a summary statement by Tufts University biologist Sherwood Gorbach emphasized that rDNA experiments were highly unlikely to create pathogens capable of causing any sort of epidemic7. By this time, other smaller groups of physicians and scientists had issued reports to bodies including the National Academies and Congress and by the summer of 1977, the New York Times had already proclaimed that there would be “No Sci-Fi Nightmare, After All.” The 1978 summary statement of a third meeting in Ascot, England established a more concrete consensus that deemed nearly all potential risks to be minimal. The two reports quickly came to be regarded as scientific fact and were cited repeatedly as the hype around rDNA died down.
By this time, rDNA experiments had also begun to show real results, which made the transformative scientific advances its proponents spoke of much more tangible. Herbert Boyer’s lab had introduced the first protein-coding gene onto a recombinant plasmid in 1977 and the following year, Genentech won the race against Wally Gilbert’s Biogen to synthesize human insulin using rDNA. None of the legislation that threatened rDNA was signed into law and in 1980, Paul Berg won half of the Nobel Prize in Chemistry for his pioneering work on rDNA. Gilbert shared the other half with Cambridge’s Fred Sanger for developing the first DNA sequencing methods. Any doubts about the scientific and political legitimacy of rDNA research faded away: the rDNA evangelists had prevailed.
The end of the beginning
While scientists had become largely free to move DNA between organisms as they saw fit, the “deeper questions” that had bothered Chargaff, Wald, Kass, and others had yet to be answered. Such concerns would resurface repeatedly as new technologies related to genetic modification and human reproduction made their way into the political sphere in subsequent decades.
By the end of the 1970s, the debates over both rDNA and in vitro fertilization looked to be largely resolved, but new groups suspicious of biotechnology, such as the Council for Responsible Genetics, sprang up in the 1980s. These groups acted as biotech watchdogs and dealt with issues including human cloning, genetic discrimination, and genetically modified crops. Environmental groups like Friends of the Earth protested the entrance of genetic engineering to agriculture, becoming increasingly antagonistic towards biotech. Many of the arguments deployed against embryonic stem cell research in the early 2000s drew on earlier objections to rDNA research.
In the case of stem cells however, a scientific consensus wasn’t enough to convince the detractors and many religious groups have remained staunchly opposed to such research. Decades after it was first debated, in vitro fertilization has recently come back under fire and the Southern Baptist Convention passed a resolution opposing the practice earlier this year. It’s no surprise that these ethical questions keep returning because, as Wald noted, they’re much more difficult to answer than questions of safety. rDNA advocates were able to simply side-step these ethical concerns by focusing on safety, but this was only possible because the initial concerns with rDNA research developed in response to a very specific set of experimental conditions. As genome editing and other new technologies come under increasing ethical scrutiny, they’ll likely have to find their own paths through the dark forest of biomedical ethics.
Conclusion
Science, technology, and society scholar Sheila Jasanoff originated the idea of “co-production,” which describes the process by which scientific knowledge and objects evolve along with the discourses, institutions, and other constructs that helped shape them. In the case of rDNA, E. coli containing recombinant plasmids can be seen as a historical object around which the early rDNA discourse grew. The public discussion of rDNA was shaped in crucial ways by the fact that it involved imbuing bacteria with new genetic material and that it stood to make scientists a lot of money. While Ruth Hubbard did question whether cloned DNA might possess some intrinsically dangerous quality, questions about the safety and commercial conflicts of interest associated with rDNA arose not from this fact, but from the specific types of DNA that were manipulated.
It might be tempting to dismiss the safety concerns expressed about rDNA as misinformed or even actively harmful, but a nuanced perspective is perhaps more appropriate. Harvard geneticist George Church, who joined Wally Gilbert’s lab as a graduate student in 1977, called the hazards of rDNA discussed at the time “overblown and under blown at the same time”, noting that for all of the discussion of safety, the possibility of bioterrorism had been completely ignored. While rDNA experiments didn’t end up creating any dangerous pathogens, biosecurity researchers continue to worry that new advances in synthetic biology and artificial intelligence might. Accordingly, debates about how to balance free scientific inquiry with safety have only intensified since the 1970s8. Understanding the rDNA controversy therefore stands to help us make informed decisions about biological risks.
This same understanding will also prepare us to thoughtfully engage with new advances in biotechnology. Genome editing technology continues to make rapid advances in the lab and the clinic, and ethical debates about human germ-line genome editing remain ongoing. The coalition against rDNA consisted of more than just “student protestors” and brought together multiple groups with a variety of different concerns. While social, economic, and environmental attitudes stemming from the protests of the ‘60s helped ignite concerns about the commercialization of biology and the potential environmental impacts of rDNA, such debates quickly became entangled with larger questions of scientific legitimacy, biosafety, and human dignity.
The rDNA controversy exposed generational divides in biology, highlighting the changing values that accompanied the development of powerful new bioengineering techniques. Moreover, while no one has cloned Wilt Chamberlain yet, the rDNA controversy brought about social and philosophical questions that remain open. Understanding the rDNA controversy prepares us not only to better participate in ongoing bioethical discussions, but also to consider in context the new technologies that will undoubtedly push the frontiers of bioengineering.
Thanks to Heather Cook and Rebecka Mähring for comments on drafts of this essay.
Mukherjee, Siddhartha. The Gene: An Intimate History (New York: Scribner, 2017), 144.
Krimsky, Sheldon. Genetic Alchemy. (Cambridge, MA: MIT Press, 1982), 83.
The P1-4 designations discussed in the rDNA debates indicate facilities certified to contain research done at the same numerical biosafety level; this system was quite new in the mid-1970s. Most rDNA experiments could be conducted under more or less standard lab conditions and the Cambridge moratorium did not actually stop any active research at Harvard or MIT.
I was unable to transcribe the author’s first name from their signature and had to improve a bit here. Even my use of “Mr.” might be incorrect as I simply went off the fact that all the other letters in the collection were written by men.
I should note that Ruth Hubbard had been granted a professorship less than a decade prior and only because of her own fight against the sexist tenure system that persisted at Harvard and other universities.
Joshua Lederberg stated this directly while Howard Temin and Arthur Kornberg referred to ‘colleague(s) at Harvard.’
My focus here is on the United States but interestingly enough the epidemic argument proved less influential in British consensus-building due to the greater focus on individual workers’ safety. This was of course a result of the different lab safety regulations in the two countries, which stemmed from their different histories of labor relations.
For a biosecurity-relevant snapshot of this debate, see these two articles from Science. A broader discussion can be found in Charles Mann’s The Wizard and the Prophet.