The code breaker, p.24
The Code Breaker, page 24
Even though human gene–editing technologies had not yet been devised, the battle lines had thus been defined. It became the mission of many of the scientists to find a middle ground rather than let the issue become politically polarized.
Asilomar
In the summer of 1972, Paul Berg, who had just published his seminal paper on how to make recombinant DNA, went to the ancient clifftop village of Erice on the coast of Sicily to lead a seminar on the new biotechnologies. The graduate students who attended were shocked by what he described, and they peppered him with questions about the ethical dangers of genetic engineering, especially the modification of humans. Berg had not focused on such questions, and he agreed to hold an informal discussion one evening on the ramparts of the old Norman-era castle overlooking the Straits of Sicily. Under a full moon, eighty students and researchers drank beer and wrestled with the ethical issues. The questions they asked were basic but hard for Berg to answer: What if we could genetically engineer height or eye color? What about intelligence? Would we do that? Should we? Francis Crick, the co-discoverer of DNA’s double-helix structure, was there, but he stayed silent as he sipped his beer.6
The discussions led Berg to convene a group of biologists in January 1973 at the Asilomar conference center on the California coast near Monterey. Known as “Asilomar I” because it launched a process that would culminate two years later at the same conference site, the meeting focused mainly on lab safety issues. It was followed in April by a conference organized by the National Academies of Science at MIT, which discussed how to prevent the creation of recombinant DNA organisms that could be dangerous. The more the participants discussed it, the less sure they became that any method would be foolproof. So they issued a letter—which was signed by Berg, James Watson, Herbert Boyer, and others—calling for a “moratorium” on the creation of recombinant DNA until safety guidelines could be formulated.7
This led to a memorable gathering that would become famous in the annals of scientists attempting to regulate their own field: the four-day Asilomar conference of February 1975. As the migration of monarch butterflies dappled the sky, 150 biologists and doctors and lawyers from around the world, plus a few journalists who agreed to turn off their tape recorders if the discussion got too heated, gathered to walk the dunes, sit at conference tables, and debate what restraints should be put on new genetic engineering technologies. “Their discussions suggest both the vitality of small boys with new chemistry sets and the electricity of back yard gossip,” Michael Rogers of Rolling Stone wrote in a piece aptly titled “The Pandora’s Box Conference.”8
One of the primary organizers was a soft-spoken but gently commanding MIT biology professor named David Baltimore, who that year would win the Nobel Prize for his work showing that viruses containing RNA, such as coronaviruses, can insert their genetic material into the DNA of a host cell through a process known as “reverse transcription.” In other words, the RNA can be transcribed into DNA, thus modifying the central dogma of biology, which states that genetic information travels in only one direction, from DNA to RNA. Baltimore would go on to become president of Rockefeller University and then Caltech, and his half-century career as a respected leader of policy councils would become a model for Doudna’s own public involvement.
After Baltimore set the stage by explaining why the meeting had been convened, Berg described the science that was at issue: recombinant DNA technology made it “ridiculously simple” to combine DNA from different organisms and create new genes. Soon after he had published his discovery, Berg told the group, he started to get calls from researchers asking him to send them material so they could do their own experiments. When he asked the callers what they wanted to do, Berg recalls, “we’d get a description of some kind of horror experiment.” He began to fear that some mad scientist would create a new microbe that could threaten the planet, like what Michael Crichton described in his 1969 bio-thriller, The Andromeda Strain.
During the policy debates, Berg insisted that the risks of using recombinant DNA to create new organisms were so hard to calculate that such research should be banned. Others found that position absurd. And Baltimore, as he would generally do throughout his career, sought to find a middle ground. He argued for restricting the use of recombinant DNA to viruses that had been “crippled” so that they could not spread.9
James Watson, true to form, played the cranky contrarian throughout. “They had worked themselves into a level of hysteria,” he later told me. “I was for researchers doing whatever they wanted.” At one point he got into a nasty clash with Berg, whose disciplined demeanor was a stark contrast to Watson’s impetuousness. The argument got so heated that Berg threatened to sue Watson. “You have signed a letter saying there is a potential risk to this line of work,” Berg reminded him, referring to their letter from the year before. “For you to now say you’re not willing to institute any procedures which would protect the staff of Cold Spring Harbor, where you’re the director, I could bring a suit against you for being irresponsible, and I will.”
As the bickering among the elders intensified, some of the younger attendees sneaked out to the beach to smoke dope. By the evening before the conference was scheduled to end, no consensus had been reached. But a panel of lawyers helped spur the scientists by warning that their institutions would likely be held liable if anyone in any lab ever got infected with recombinant DNA. The university responsible might then have to shut down.
Later that night, Berg and Baltimore stayed up with a few colleagues eating takeout Chinese food in a beachside cabana. Using a blackboard they had commandeered, they spent hours trying to write a statement. Around 5 a.m., just before the sun rose, they emerged with a draft.
“The new techniques, which permit combination of genetic information from very different organisms, place us in an arena of biology with many unknowns,” they wrote. “It is this ignorance that has compelled us to conclude that it would be wise to exercise considerable caution in performing this research.” Then they described in detail the type of safeguards and restrictions that would be put on experiments.
Baltimore made copies of their provisional statement in time to have it distributed at the 8:30 a.m. session, at which point Berg took on the task of herding the scientists to support it. Someone insisted they vote on each paragraph. Berg knew that would be a disaster, and he vetoed the idea. But he did yield to the eminent molecular biologist Sydney Brenner, who asked for an up-or-down vote on the central recommendation being proposed: that the moratorium on genetic engineering research be lifted and that it should proceed with certain safeguards. “The pause is over,” Brenner said. The room agreed. A few hours later, just as the bell rang for the final lunch, Berg asked for a vote on the document as a whole, which included detailed safety provisions that labs would have to follow. Most hands went up in favor. Ignoring those who still clamored to speak, he then asked if there were any opposed. Only four or five hands were raised, including that of Watson, who thought all the safeguards were silly.10
* * *
The conference had two goals: guarding against the hazards that could come from creating new forms of genes and guarding against the threat that politicians would ban genetic engineering altogether. On both fronts, the Asilomar process was successful. They were able to chart “a prudent path forward,” an approach that Baltimore and Doudna would later replicate in the debates over CRISPR gene editing.
The restrictions agreed to at Asilomar were accepted by universities and funding agencies worldwide. “This unique conference marked the beginning of an exceptional era for science and for the public discussion of science policy,” Berg wrote thirty years later. “We gained the public’s trust, for it was the very scientists who were most involved in the work and had every incentive to be left free to pursue their dream that called attention to the risks inherent in the experiments they were doing. Restrictive national legislation was avoided.”11
Others were less willing to join the mutual back-patting. Erwin Chargaff, a brilliant biochemist who had made key discoveries about the structure of DNA, looked back on the event as a charade. “At this Council of Asilomar there congregated the molecular bishops and church fathers from all over the world, in order to condemn the heresies of which they themselves had been the first and the principal perpetrators,” he said. “This was probably the first time in history that the incendiaries formed their own fire brigade.”12
Berg was right that Asilomar was a great success. It paved the way for genetic engineering to become a booming field. But Chargaff’s mocking assessment pointed to another lasting legacy. Asilomar became notable for what the scientists did not discuss there. Their focus was on safety. None of them addressed the big ethical question, the one that Berg had stayed up late discussing in Sicily: How far should we go if and when methods of engineering our genes turned out to be safe?
Splicing Life, 1982
Asilomar’s lack of focus on ethical issues bothered many religious leaders. That prompted a letter to President Jimmy Carter signed by the heads of three major religious organizations: the National Council of Churches, the Synagogue Council of America, and the U.S. Catholic Conference. “We are rapidly moving into a new era of fundamental danger triggered by the rapid growth of genetic engineering,” they wrote. “Who shall determine how human good is best served when new life forms are being engineered?”13
These decisions should not be left to scientists, the trio argued. “There will always be those who believe it appropriate to ‘correct’ our mental and social structures by genetic means. This becomes more dangerous when the basic tools to do so are finally at hand. Those who would play God will be tempted as never before.”
Carter responded by appointing a presidential commission to study the issue. It came back in late 1982 with a 106-page report titled Splicing Life that ended up being inconclusive mush. It merely called for further dialogue to reach societal consensus. “A goal of this Report is to stimulate thoughtful, long-term discussion—not preempt it with conclusions that would, of necessity, be premature.”14
The commission’s report did raise two concerns that were prescient. The first was a fear that genetic engineering was leading to increased corporate involvement in university research. Universities had historically focused on basic research and the open exchange of ideas, and the report warned, “These goals may run headlong into those of industry—the development of marketable products and techniques through applied research by maintaining a competitive posture, protecting trade secrets, and seeking patent protection.”
The second concern was that genetic engineering would increase inequality. New biotech procedures would be expensive, so people who were born into privilege would likely get the most benefits. That could widen, and genetically encode, existing inequalities. “The possibilities presented by gene therapy and gene surgery may in fact call into question a central element of democratic political theory and practice: the commitment to equality of opportunity.”
Preimplantation genetic diagnosis and Gattaca
After the development of recombinant DNA in the 1970s, the next big bioengineering advance—and set of ethical issues—came in the 1990s. It resulted from the confluence of two innovations: in vitro fertilization (the first test-tube baby, Louise Brown, was born in 1978) combined with genetic sequencing technology. This led, in 1990, to the first use of what became known as preimplantation genetic diagnosis.15
Preimplantation diagnosis involves fertilizing an egg with sperm in a Petri dish, doing tests on the resulting embryosI to determine their genetic characteristics, and then implanting into a woman’s womb the embryo with the most desired traits. It allows parents to choose the gender of their child and avoid having a child who carries a genetic disease or some other attribute the parents find undesirable.
The potential of such genetic screening and selection entered the popular imagination through the 1997 film Gattaca (the title is made up of the letters of the four DNA bases), starring Ethan Hawke and Uma Thurman. It tells of a future in which genetic selection is regularly used to ensure that children are enhanced with the best hereditary traits.
To promote the movie, the studio took out advertisements in newspapers that appeared as if they were for a real gene-editing clinic. Headlined “Children Made to Order,” the ad read, “At Gattaca, it is now possible to engineer your offspring. Here’s a checklist to help you decide what traits to pass on to your newborn.” The list included gender, stature, eye color, skin color, weight, addictive susceptibility, criminal aggressive tendencies, musical ability, athletic prowess, and intellect. The final choice was “None of the above.” The ad advises of that option, “For religious or other reasons, you may have reservations about genetically engineering your child. We respectfully invite you to reconsider. From where we sit, the human race could use a little improving.”
At the bottom of the ad was a toll-free telephone number, which led to a recording offering callers three options: “Press one if you’d like to take the steps to ensure that your offspring is disease-free. Press two if you’d like to enhance intellectual and physical traits. Press three if you don’t want to tamper with your kid’s genetic makeup.” Within two days, the toll-free number had received fifty thousand calls, but the studio, alas, did not track how many chose each of the options.
The hero of the movie, played by Hawke, was conceived without the benefits or burdens of preimplantation engineering, and he must battle genetic discrimination in order to fulfill his dream of becoming an astronaut. He is, of course, triumphant, since this is a movie. A particularly interesting scene occurs when his parents decide to make use of gene editing in having their second child. The doctor describes all the traits and enhancements he can engineer: better eyesight, desired eye and skin color, no predisposition toward alcoholism or baldness, and more. “Is it good to leave a few things to chance?” the parents ask. No, the doctor assures them, they are merely giving their prospective child “the best possible start.”
That led film critic Roger Ebert to write, “When parents can order ‘perfect’ babies, will they? Would you take your chances on a throw of the genetic dice, or order up the make and model you wanted? How many people are prepared to buy a car at random from the universe of all available cars? That’s how many, I suspect, would opt to have natural children.” But then Ebert smartly expressed the worries that were beginning to form at the time: “Everybody will live longer, look better and be healthier in the Gattacan world. But will it be as much fun? Will parents order children who are rebellious, ungainly, eccentric, creative, or a lot smarter than their parents are? Don’t you sometimes have the feeling you were born just in time?”16
Watson and others at UCLA, 1998
Once again, the irascible old DNA pioneer James Watson sat in the audience loudly mumbling provocative thoughts that he seemed gleefully unable to suppress. This time it was at a gene-editing conference hosted by UCLA professor Gregory Stock in 1998. French Anderson, a leader in using genetic engineering to create drugs, gave a mini-sermon on the need to distinguish between treating diseases, which he proclaimed to be moral, and providing children with genetic enhancements, which he said wasn’t. Watson began to snort and stir. “No one really has the guts to say it,” he interrupted, “but if we could make better human beings by knowing how to add genes, why shouldn’t we do it?”17
The title of the gathering was “Engineering the Human Germline,” and it focused on the ethics of making genetic edits that would be inherited. These “germline” edits were fundamentally different, medically and morally, from somatic-cell edits that affect only certain cells in an individual patient. The germline was a red line that scientists had been reluctant to cross. “This is the first gathering where people have talked openly about germline engineering,” Watson said approvingly. “It seems obvious that germline therapy will be much more successful than somatic-cell edits. If we wait for the success of somatic therapy, we’ll wait until the sun burns out.”
It was absurd, Watson said, to treat the germline as “some great Rubicon and crossing it involved going against natural law.” When he was challenged about the need to respect “the sanctity of the human gene pool,” he erupted. “Evolution can be just damn cruel, and to say that we’ve got a perfect genome and there’s some sanctity to it is utter silliness.” His schizophrenic son, Rufus, was a daily reminder that the genetic lottery could be, as he put it, damn cruel. “The biggest ethical problem we have is not using our knowledge and not having the guts to go ahead and try to help someone,” he insisted.18
For the most part, Watson was preaching to the choir. The opinions at the UCLA conference ranged from enthusiasm to unbridled enthusiasm for gene editing. When someone suggested that going down that slope might lead to unintended consequences, Watson was unwavering. “I think the slippery slope argument is just crap. Societies thrive when they’re optimistic, not pessimistic, and the slippery slope argument sounds like one from a worn-out person who’s angry at himself.”
Lee Silver, a Princeton biologist, had just published Remaking Eden, which became a manifesto for the conference. He had coined the word “reprogenetics” to describe the use of technology to determine which genes a child would inherit. “In a society that values individual freedom above all else, it is hard to find any legitimate basis for restricting the use of reprogenetics,” he wrote.19
Silver’s work was important because it framed the issue as being about individual freedom and liberty in a market-based consumer society. “If democratic societies allow parents to buy environmental advantages for their children, how can they prohibit them from buying genetic advantages?” he prodded. “Americans would respond to any attempt at a ban with the question, ‘Why can’t I give my child beneficial genes that other children get naturally?’ ”20
