Nothing had been formalized by the last evening of the conference, until the lawyers took the stage. The five attorneys asked to discuss the legal ramifications of cloning and laid out a grim vision of potential risks: if a single member of a laboratory was infected by a recombinant microbe, and that infection led to even the palest manifestations of a disease, they argued, the laboratory head, the lab, and the institution would be held legally liable. Whole universities would shut down. Labs would be closed indefinitely, their front doors picketed by activists and locked by hazmat men in astronaut suits. The NIH would be flooded with queries; all hell would break loose. The federal government would respond by proposing draconian regulations—not just on recombinant DNA, but on a larger swath of biological research. The result could be restrictions vastly more stringent than any rules that scientists might be willing to impose on themselves.
The lawyers’ presentation, held strategically on the last day of Asilomar II, was the turning point for the entire meeting. Berg realized that the meeting should not—could not—end without formal recommendations. That evening, Baltimore, Berg, Singer, Brenner, and Roblin stayed up late in their cabana, eating Chinese takeout from paper cartons, scribbling on a blackboard, and drafting a plan for the future. At five thirty in the morning, disheveled and bleary-eyed, they emerged from the beach house smelling of coffee and typewriter ink, with a document in hand. The document began with the recognition of the strange parallel universe of biology that scientists had unwittingly entered with gene cloning. “The new techniques, which permit combination of genetic information from very different organisms, place us in an arena of biology with many unknowns. . . . It is this ignorance that has compelled us to conclude that it would be wise to exercise considerable caution in performing this research.”
To mitigate the risks, the document proposed a four-level scheme to rank the biohazard potentials of various genetically altered organisms, with recommended containment facilities for each level (inserting a cancer-causing gene into a human virus, for instance, would merit the highest level of containment, while placing a frog gene into a bacterial cell might merit minimal containment). As Baltimore and Brenner had insisted, it proposed the development of crippled gene-carrying organisms and vectors to further contain them in laboratories. Finally, it urged continuous review of recombination and containment procedures, with the possibility of loosening or tightening restrictions in the near future.
When the meeting opened at eight thirty on the last morning, the five members of the committee worried that the proposal would be rejected. Surprisingly, it was near unanimously accepted.
In the aftermath of the Asilomar Conference, several historians of science have tried to grasp the scope of the meeting by seeking an analogous moment in scientific history. There is none. The closest one gets to a similar document, perhaps, is a two-page letter written in August 1939 by Albert Einstein and Leo Szilard to alert President Roosevelt to the alarming possibility of a powerful war weapon in the making. A “new and important source of energy” had been discovered, Einstein wrote, through which “vast amounts of power . . . might be generated.” “This new phenomenon would also lead to the construction of bombs, and it is conceivable . . . that extremely powerful bombs of a new type may thus be constructed. A single bomb of this type, carried by boat and exploded in a port, might very well destroy the whole port.” The Einstein-Szilard letter had generated an immediate response. Sensing the urgency, Roosevelt had appointed a scientific commission to investigate it. Within a few months, Roosevelt’s commission would become the Advisory Committee on Uranium. By 1942, it would morph further into the Manhattan Project and ultimately culminate in the creation of the atomic bomb.
But Asilomar was different: here, scientists were alerting themselves to the perils of their own technology and seeking to regulate and constrain their own work. Historically, scientists had rarely sought to become self-regulators. As Alan Waterman, the head of the National Science Foundation, wrote in 1962, “Science, in its pure form, is not interested in where discoveries may lead. . . . Its disciples are interested only in discovering the truth.”
But with recombinant DNA, Berg argued, scientists could no longer afford to focus merely on “discovering the truth.” The truth was complex and inconvenient, and it required sophisticated assessment. Extraordinary technologies demand extraordinary caution, and political forces could hardly be trusted to assess the perils or the promise of gene cloning (nor, for that matter, had political forces been particularly wise about handling genetic technologies in the past—as the students had pointedly reminded Berg at Erice). In 1973, less than two years before Asilomar, Nixon, fed up with his scientific advisers, had vengefully scrapped the Office of Science and Technology, sending spasms of anxiety through the scientific community. Impulsive, authoritarian, and suspicious of science even at the best of times, the president might impose arbitrary control on scientists’ autonomy at any time.
A crucial choice was at stake: scientists could relinquish the control of gene cloning to unpredictable regulators and find their work arbitrarily constrained—or they could become science regulators themselves. How were biologists to confront the risks and uncertainties of recombinant DNA? By using the methods that they knew best: gathering data, sifting evidence, evaluating risks, making decisions under uncertainty—and quarreling relentlessly. “The most important lesson of Asilomar,” Berg said, “was to demonstrate that scientists were capable of self-governance.” Those accustomed to the “unfettered pursuit of research” would have to learn to fetter themselves.
The second distinctive feature of Asilomar concerned the nature of communications between scientists and the public. The Einstein-Szilard letter had been deliberately shrouded in secrecy; Asilomar, in contrast, sought to air the concerns about gene cloning in the most public forum possible. As Berg put it, “The public’s trust was undeniably increased by the fact that more than ten percent of the participants were from the news media. They were free to describe, comment on, and criticize the discussions and conclusions. . . . The deliberations, bickering, bitter accusations, wavering views, and the arrival at a consensus were widely chronicled by the reporters that attended.”
A final feature of Asilomar deserves commentary—notably for its absence. While the biological risks of gene cloning were extensively discussed at the meeting, virtually no mention was made of the ethical and moral dimensions of the problem. What would happen once human genes were manipulated in human cells? What if we began to “write” new material into our own genes, and potentially our genomes? The conversation that Berg had started in Sicily was never rejuvenated.
Later, Berg reflected on this lacuna: “Did the organizers and participants of the Asilomar conference deliberately limit the scope of the concerns? . . . Others have been critical of the conference because it did not confront the potential misuse of the recombinant DNA technology or the ethical dilemmas that would arise from applying the technology to genetic screening and . . . gene therapy. It should not be forgotten that these possibilities were still far in the future. . . . In short, the agenda for the three-day meeting had to focus on an assessment of the [biohazard] risks. We accepted that the other issues would be dealt with as they became imminent and estimable.” The absence of this discussion was noted by several participants, but it was never addressed during the meeting itself. It is a theme to which we will return.
In the spring of 1993, I traveled to Asilomar with Berg and a group of researchers from Stanford. I was a student in Berg’s lab then, and this was the annual retreat for the department. We left Stanford in a caravan of cars and vans, hugging the coast at Santa Cruz and then heading out toward the narrow cormorant neck of the Monterey Peninsula. Kornberg and Berg drove ahead. I was in a rental van driven by a graduate student and accompanied, improbably, by an opera-diva-turned-biochemist who worked on DNA replication and occasionally burst into strains of Puccini.
On the last day of our meeting, I took
a walk through the scrub-pine groves with Marianne Dieckmann, Berg’s long-term research assistant and collaborator. Dieckmann guided me through an unorthodox tour of Asilomar, pointing out the places where the fiercest mutinies and arguments had broken out. This was an expedition through a landscape of disagreements. “Asilomar,” she told me, “was the most quarrelsome meeting that I have ever attended.”
What did these quarrels achieve? I asked. Dieckmann paused, looking toward the sea. The tide had gone out, leaving the beach carved in the shadows of waves. She used her toe to draw a line on the wet sand. “More than anything, Asilomar marked a transition,” she said. “The capacity to manipulate genes represented nothing short of a transformation in genetics. We had learned a new language. We needed to convince ourselves, and everyone else, that we were responsible enough to use it.”
It is the impulse of science to try to understand nature, and the impulse of technology to try to manipulate it. Recombinant DNA had pushed genetics from the realm of science into the realm of technology. Genes were not abstractions anymore. They could be liberated from the genomes of organisms where they had been trapped for millennia, shuttled between species, amplified, purified, extended, shortened, altered, remixed, mutated, mixed, matched, cut, pasted, edited; they were infinitely malleable to human intervention. Genes were no longer just the subjects of study, but the instruments of study. There is an illuminated moment in the development of a child when she grasps the recursiveness of language: just as thoughts can be used to generate words, she realizes, words can be used to generate thoughts. Recombinant DNA had made the language of genetics recursive. Biologists had spent decades trying to interrogate the nature of the gene—but now it was the gene that could be used to interrogate biology. We had graduated, in short, from thinking about genes, to thinking in genes.
Asilomar, then, marked the crossing of these pivotal lines. It was a celebration, an appraisal, an assembly, a confrontation, a warning. It began with a speech and ended with a document. It was the graduation ceremony for the new genetics.
“Clone or Die”
If you know the question, you know half.
—Herb Boyer
Any sufficiently advanced technology is indistinguishable from magic.
—Arthur C. Clarke
Stan Cohen and Herb Boyer had also gone to Asilomar to debate the future of recombinant DNA. They found the conference irritating—even deflating. Boyer could not bear the infighting and the name-calling; he called the scientists “self-serving” and the meeting a “nightmare.” Cohen refused to sign the Asilomar agreement (although as a grantee of the NIH, he would eventually have to comply with it).
Back in their own laboratories, they returned to an issue that they had neglected amid the commotion. In May 1974, Cohen’s lab had published the “frog prince” experiment—the transfer of a frog gene into a bacterial cell. When asked by a colleague how he had identified the bacteria expressing the frog genes, Cohen had jokingly said that he had kissed the bacteria to check which ones would transform into a prince.
At first, the experiment had been an academic exercise; it had only turned biochemists’ heads. (Joshua Lederberg, the Nobel Prize–winning biologist and Cohen’s colleague at Stanford, was among the few who wrote, presciently, that the experiment “may completely change the pharmaceutical industry’s approach to making biological elements, such as insulin and antibiotics.”) But slowly, the media awoke to the potential impact of the study. In May, the San Francisco Chronicle ran a story on Cohen, focusing on the possibility that gene-modified bacteria might someday be used as biological “factories” for drugs or chemicals. Soon, articles on gene-cloning technologies had appeared in Newsweek and the New York Times. Cohen also received a quick baptism on the seamy side of scientific journalism. Having spent an afternoon talking patiently to a newspaper reporter about recombinant DNA and bacterial gene transfer, he awoke the next morning to the hysterical headline: “Man-made Bugs Ravage the Earth.”
At Stanford University’s patent office, Niels Reimers, a savvy former engineer, read about Cohen and Boyer’s work through these news outlets and was intrigued by its potential. Reimers—less patent officer and more talent scout—was active and aggressive: rather than waiting for inventors to bring him inventions, he scoured the scientific literature on his own for possible leads. Reimers approached Boyer and Cohen, urging them to file a joint patent on their work on gene cloning (Stanford and UCSF, their respective institutions, would also be part of that patent). Both Cohen and Boyer were surprised. During their experiments, they had not even broached the idea that recombinant DNA techniques could be “patentable,” or that the technique could carry future commercial value. In the winter of 1974, still skeptical, but willing to humor Reimers, Cohen and Boyer filed a patent for recombinant DNA technology.
News of the gene-cloning patent filtered back to scientists. Kornberg and Berg were furious. Cohen and Boyer’s claims “to commercial ownership of the techniques for cloning all possible DNAs, in all possible vectors, joined in all possible ways, in all possible organisms [is] dubious, presumptuous, and hubristic,” Berg wrote. The patent would privatize the products of biological research that had been paid for with public money, they argued. Berg also worried that the recommendations of the Asilomar Conference could not be adequately policed and enforced in private companies. To Boyer and Cohen, however, all of this seemed much ado about nothing. Their “patent” on recombinant DNA was no more than a sheaf of paper making its way between legal offices—worth less, perhaps, than the ink that had been used to print it.
In the fall of 1975, with mounds of paperwork still moving through legal channels, Cohen and Boyer parted scientific ways. Their collaboration had been immensely productive—together they had published eleven landmark papers over five years—but their interests had begun to drift apart. Cohen became a consultant to a company called Cetus in California. Boyer returned to his lab in San Francisco to concentrate on his experiments on bacterial gene transfer.
In the winter of 1975, a twenty-eight-year-old venture capitalist, Robert Swanson, called Herb Boyer out of the blue to suggest a meeting. A connoisseur of popular-science magazines and sci-fi films, Swanson had also heard about a new technology called “recombinant DNA.” Swanson had an instinct for technology; even though he knew barely any biology, he had sensed that recombinant DNA represented a tectonic shift in thinking about genes and heredity. He had dug up a dog-eared handbook from the Asilomar meeting, made a list of important players working on gene-cloning techniques, and had started working down the list alphabetically. Berg came before Boyer—but Berg, who had no patience for opportunistic entrepreneurs making cold calls to his lab, turned Swanson down. Swanson swallowed his pride and kept going down the list. B . . . Boyer was next. Would Boyer consider a meeting? Immersed in experiments, Herb Boyer fielded Swanson’s phone call distractedly one morning. He offered ten minutes of his time on a Friday afternoon.
Swanson came to see Boyer in January 1976. The lab was located in the grimy innards of the Medical Sciences Building at UCSF. Swanson wore a dark suit and tie. Boyer appeared amid mounds of half-rotting bacterial plates and incubators in jeans and his trademark leather vest. Boyer knew little about Swanson—only that he was a venture capitalist looking to form a company around recombinant DNA. Had Boyer investigated further, he might have discovered that nearly all of Swanson’s prior investments in fledgling ventures had failed. Swanson was out of work, living in a rent-shared apartment in San Francisco, driving a broken Datsun, and eating cold-cut sandwiches for lunch and dinner.
The assigned ten minutes grew into a marathon meeting. They walked to a neighborhood bar, talking about recombinant DNA and the future of biology. Swanson proposed starting a company that would use gene-cloning techniques to make medicines. Boyer was fascinated. His own son had been diagnosed with a potential growth disorder, and Boyer had been gripped by the possibility of producing human growth hormone, a protein to treat such growth d
efects. He knew that he might be able to make growth hormone in his lab by using his own method of stitching genes and inserting them into bacterial cells, but it would be useless: no sane person would inject his or her child with bacterial broth grown in a test tube in a science lab. To make a medical product, Boyer needed to create a new kind of pharmaceutical company—one that would make medicines out of genes.
Three hours and three beers later, Swanson and Boyer had reached a tentative agreement. They would pitch in $500 each to cover legal fees to start such a company. Swanson wrote up a six-page plan. He approached his former employers, the venture firm Kleiner Perkins, for $500,000 in seed money. The firm took a quick look at the proposal and slashed that number fivefold to $100,000. (“This investment is highly speculative,” Perkins later wrote apologetically to a California regulator, “but we are in the business of making highly speculative investments.”)
Boyer and Swanson had nearly all the ingredients for a new company—except for a product and a name. The first potential product, at least, was obvious from the start: insulin. Despite many attempts to synthesize it using alternative methods, insulin was still being produced from mashed-up cow and pig innards, a pound of hormone from eight thousand pounds of pancreas—a near-medieval method that was inefficient, expensive, and outdated. If Boyer and Swanson could express insulin as a protein via gene manipulation in cells, it would be a landmark achievement for a new company. That left the issue of the name. Boyer rejected Swanson’s suggestion of HerBob, which sounded like a hair salon on the Castro. In a flash of inspiration, Boyer suggested a condensation of Genetic Engineering Technology—Gen-en-tech.
Insulin: the Garbo of hormones. In 1869, a Berlin medical student, Paul Langerhans, had looked through a microscope at the pancreas, a fragile leaf of tissue tucked under the stomach, and discovered minute islands of distinct-looking cells studded across it. These cellular archipelagoes were later named the islets of Langerhans, but their function remained mysterious. Two decades later, two surgeons, Oskar Minkowski and Josef von Mering, had surgically removed the pancreas from a dog to identify the function of the organ. The dog was struck by an implacable thirst and began to urinate on the floor.
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