The code breaker, p.25
The Code Breaker, page 25
Silver’s techno-enthusiasm set the tone for what participants viewed as a historic moment. “For the first time we as a species have the ability to self-evolve,” Silver told the group. “I mean, this is an incredible concept.” He meant the word “incredible” to be a compliment.
As with the Asilomar conference, one of the goals of the UCLA conference was to fend off government regulation. “The main message we need to draw is to keep the state out of any form of genetic decision,” Watson argued. The attendees accepted that view. “No state or federal legislation to regulate germline gene therapy should be passed at this time,” organizer Gregory Stock wrote in his summation.
Stock went on to write a pro-editing manifesto, Redesigning Humans: Our Inevitable Genetic Future. “A key aspect of human nature is our ability to manipulate the world,” he argued. “To turn away from germline selection and modification without even exploring them would be to deny our essential nature and perhaps our destiny.” He emphasized that politicians should not try to interfere. “Policymakers sometimes mistakenly think that they have a voice about whether germinal technologies will come into being,” he wrote. “They do not.”21
The American enthusiasm for genetic engineering was a sharp contrast to the attitude in Europe, where policymakers and various commissions had increasingly turned against it, both in agriculture and in humans. The most notable expression came from a meeting convened by the Council of Europe in Oviedo, Spain, in 1997. The resulting Oviedo Convention was intended to be a legally binding treaty designed to prohibit the use of biological advances in ways that threatened human dignity. It barred genetic engineering in humans except “for preventive, diagnostic or therapeutic reasons and only where it does not aim to change the genetic make-up of a person’s descendants.” In other words, no germline editing. Twenty-nine European countries incorporated the Oviedo Convention into their laws, with Britain and Germany being notable holdouts. Even where it was not ratified it helped shape what is still a general consensus in Europe against genetic engineering.22
Jesse Gelsinger
The optimism among American researchers about genetic engineering was deflated in September 1999 by a tragedy that happened in Philadelphia to a sweet, handsome, and slightly rebellious eighteen-year-old high school student. Jesse Gelsinger suffered from a mild form of a disease of the liver caused by a simple genetic mutation. It caused his liver to have problems ridding his body of ammonia, which is a byproduct of the breakdown of proteins. It usually kills victims as babies, but Gelsinger’s milder form meant that he could survive by eating a very low-protein diet and taking thirty-two pills a day.
A team at the University of Pennsylvania was testing a genetic therapy for the disease. Such therapies do not involve actually editing the DNA of the cells inside the body. Instead, genes without the mutation are created in a lab, and then doctors put these good genes into a virus that serves as a delivery mechanism. In Gelsinger’s case, the viruses with the good genes were injected into an artery that led into the liver.
It was unlikely that the therapy would help Gelsinger right away, because it was a trial designed to see how the therapy could be used to save babies. But it offered him hope that someday he would be able to eat hot dogs, and in the meantime, some babies would be saved. “What’s the worst that can happen to me?” he said to a friend as he was leaving for the Philadelphia hospital. “I die, and it’s for the babies.”23
Unlike the seventeen other humans in the trial, Gelsinger had a massive immune response caused by the virus transporting the therapeutic gene, which resulted in a high fever followed by the breakdown of his kidneys, lungs, and other organs. In four days he was dead. Work on gene therapy ground to a halt. “We were all very much aware of what happened,” Doudna recalled. “That made the whole field of gene therapy go away, mostly, for at least a decade. Even the term gene therapy became kind of a black label. You didn’t want that in your grants. You didn’t want to say, ‘I’m working on gene therapy.’ It sounded terrible.”24
The Kass Commission, 2003
The debate over genetic engineering at the turn of the century—after the completion of the Human Genome Project and the cloning of Dolly the sheep—led to another U.S. presidential commission, this one created by President George W. Bush in 2003. It was chaired by Leon Kass, a biologist and social philosopher who had first expressed wariness about biotechnology thirty years earlier.
Kass is the most influential of the country’s bioconservatives, the ethical traditionalists with a knowledge of biology who urge restraint when dealing with new genetic technologies. The son of secular Jewish immigrants, he earned a biology degree at the University of Chicago, where he was deeply influenced by its “great books” core curriculum. He got a medical degree from Chicago and a PhD in biochemistry from Harvard. With his wife, Amy, he went to Mississippi in 1965 as part of the cadre of civil rights workers registering Blacks to vote, an experience that reinforced his faith in traditional values. “In Mississippi I saw people living in perilous and meager circumstances, many of them illiterate, but sustained by religion, extended family and community attachment,” he recalled.25
Upon returning to the University of Chicago as a professor, his writings ranged from scientific papers on molecular biology (“The Antibacterial Activity of 3-Decynoyl-N-Acetylcysteamine”) to a book on the Hebrew Bible. After reading Huxley’s Brave New World, he became more interested in “how the scientific project to master nature could, if we are not careful, lead to our dehumanization.” Combining his appreciation for both science and the humanities, he began to tackle the issues raised by reproductive technologies such as cloning and in vitro fertilization. “I soon shifted my career from doing science to thinking about its human meaning,” he wrote, “worrying about upholding our humanity against possible technological degradation.”
His first published warning about bioengineering was a letter in Science in 1971 criticizing Bentley Glass’s contention that “every child has the inalienable right to a sound heritage.” Kass declared, “To make good such an ‘inalienable right’ means converting human reproduction into manufacture.” The following year he wrote an essay explaining his wariness about genetic-engineering technologies. “The road to Brave New World is paved with sentimentality—yes, even with love and charity,” he wrote. “Have we enough sense to turn back?”26
* * *
In 2001, the Kass Commission included many distinguished conservative or neoconservative thinkers, including Robert George, Mary Ann Glendon, Charles Krauthammer, and James Q. Wilson. Two prominent philosophers proved to be especially influential members. The first was Michael Sandel, a Harvard professor who is the contemporary successor to John Rawls in defining the concept of justice. At the time, he was writing an essay titled “The Case Against Perfection: What’s Wrong with Designer Children, Bionic Athletes, and Genetic Engineering,” which he published in The Atlantic in 2004.27 The other key thinker was Francis Fukuyama, who in 2000 published Our Posthuman Future: Consequences of the Biotechnology Revolution, which was a forceful call for governments to regulate biotechnology.28
Not surprisingly, their final 310-page report, Beyond Therapy, was thoughtful, vibrantly written, and filled with qualms about genetic engineering. It warned of the dangers of using technology to go beyond merely treating diseases to using it to enhance human capabilities. “There are reasons to wonder whether life will really be better if we turn to biotechnology to fulfill our deepest human desires,” the report declared.29
Focusing mainly on philosophical rather than safety concerns, the authors discussed what it meant to be human, to pursue happiness, to respect nature’s gifts, and to accept the given. It argued the case, or more accurately it preached the case, that going too far to alter what is “natural” was hubristic and endangered our individual essence. “We want better children—but not by turning procreation into manufacture or by altering their brains to gain them an edge over their peers,” they wrote. “We want to perform better in the activities of life—but not by becoming mere creatures of our chemists or by turning ourselves into tools designed to win or achieve in inhuman ways.” One can almost sense a congregation nodding “Amen” while a few people in the back mutter, “Speak for yourself.”
I. I use the word “embryo” in the broad sense. The single-cell organism resulting from a fertilized egg is a zygote. When the zygote divides to become a collection of cells that can implant in the wall of the uterus, it is called a blastocyst. About four weeks later, after the development of an amniotic sac, it becomes an embryo. After eleven weeks, it is usually referred to as a fetus.
George Daley, Doudna, and David Baltimore at the 2015 international summit
CHAPTER 36 Doudna Steps In
The Hitler nightmare
In the spring of 2014, when the battle to win CRISPR patents and launch gene-editing companies was heating up, Doudna had a dream. More precisely, she had a nightmare. In it, a prominent researcher asked her to meet someone who wanted to learn about gene editing. When she went into the room, she recoiled. Sitting in front of her, with pen and paper ready to take notes, was Adolf Hitler with the face of a pig. “I want to understand the uses and implications of this amazing technology you’ve developed,” he said. Doudna was jolted awake by the nightmare, she recalls. “As I lay in the dark, my heart racing, I couldn’t escape the awful premonition with which the dream had left me.” She began to have trouble sleeping at night.
Gene-editing technology had enormous power to do good, but the thought of using it to make alterations in humans that would be inherited by all future generations was unnerving. “Have we created a toolbox for future Frankensteins?” she asked herself. Or perhaps even worse, would it be a tool for future Hitlers? “Emmanuelle and I, and our collaborators, had imagined that CRISPR technology could save lives by helping to cure genetic disease,” she later wrote. “Yet as I thought about it now, I could scarcely begin to conceive of all of the ways in which our hard work might be perverted.”1
Happy Healthy Baby
Around that time, Doudna was confronted with an example of how people with good intentions could pave the way for gene editing. Sam Sternberg, one of the researchers on her close-knit CRISPR team, received an email in March 2014 from an aspiring young entrepreneur in San Francisco named Lauren Buchman, who had gotten Sternberg’s name from a friend. “Hi, Sam,” she wrote. “Nice to meet you by email. I see that you’re located just across the Bridge. Any chance I could buy you a coffee and chat a bit about what you’re up to?”2
“I’d be happy to meet sometime though my schedule is busy,” Sternberg replied. “Maybe in the meantime, you could fill me in a bit on what your company is doing.”
“I’ve started a company called Happy Healthy Baby,” she explained in her next email. “We’ve seen a potential of Cas9 to aid in preventing genetic diseases in children conceived through IVF in the future. Ensuring that this is done with the highest level of scientific and ethical standards is first and foremost to us.”
Sternberg was surprised but not totally shocked. By that time CRISPR-Cas9 had already been used to edit embryos implanted in monkeys. He was interested in digging a bit deeper into what Buchman’s motivations were and how she was thinking about developing this concept, so he agreed to meet her at a Mexican restaurant in Berkeley. There Buchman pitched him on the idea of offering people the chance to use CRISPR to edit their future babies.
She had already registered the domain name HealthyBabies.com. Might he want to be a cofounder? This surprised Sternberg, and not simply because he shared with his lab pal Blake Wiedenheft a good-humored humility. He had no experience editing human cells, much less knowing the first thing about how to implant embryos.
When I first heard about Buchman’s concept, I found it disconcerting. But when I tracked her down, I was surprised to find that she was actually quite thoughtful about the moral issues. Her sister was a leukemia survivor and could not, as a result of her treatment, have children. Buchman herself was trying to launch a career and worried about her biological clock running down. “I was a woman in my thirties,” she recalls. “And we’re all facing the same issue. We want a career and not to be mommy-tracked, and we are starting to deal with fertility clinics.”
She knew that in vitro fertility clinics could screen for harmful genes before choosing an embryo to implant, but as a thirtysomething woman she also knew that producing a bunch of fertilized embryos was easier said than done. “You may end up producing only one or two embryos,” she points out, “so preimplantation genetic screening is not always easy.”
That’s when she heard about CRISPR and got excited. “The idea that we could treat something in cells seemed so promising and wonderful.”
She was sensitive to the social issues. “All tech can be used for good or for bad, but the early movers in new technologies have the opportunity to promote positive and ethical usage,” she says. “I wanted to do gene-editing right, and to do it in the open, so there would be an established pattern for ethical procedures for patients who wanted to use it.”
Some of the venture capitalists and biotech entrepreneurs she consulted ended up pitching her on weird ideas that freaked her out, such as enlisting biohackers to crowdsource the editing of patients’ genes. “The more I heard, the more I thought ‘I have to do this,’ ” she says, “because if I don’t, these fringe folks with no regard for the impact or the ethics will take over the field.”
Sternberg left the dinner at the Mexican restaurant before dessert. He had no interest in being a cofounder, but he was intrigued enough to agree to visit the company’s workspace. “There was never a chance in a million that I was going to get involved, but I was curious,” he says. He knew that Doudna was beginning to worry about these sorts of things, so he decided to visit the lab so that he could talk to someone who wanted to be in the driver’s seat on the type of CRISPR application that would stir up controversy.
During his visit, Sternberg watched a promotional video for Happy Healthy Baby, filled with animation and stock footage of lab experiments, in which Buchman, sitting in a sunny room with big glass windows, explains the idea of gene-editing babies. He told her that he didn’t see any chance that CRISPR would be approved for use on human babies in the U.S. for at least ten years. She replied that the clinics did not have to be in the U.S. There would likely be other countries where the procedure would be allowed, and people who could afford gene-edited babies would be willing to travel.
Sternberg decided not to get involved, but for a while George Church agreed to serve as an unpaid science advisor. “George suggested that I work with sperm cells rather than embryos,” Buchman recalls. “He said it might be less controversial or troubling.”3
Buchman eventually abandoned the venture. “I dug into the use cases, market regulations, and ethics, and it became obvious that I was too early to be working on this,” she says. “The science wasn’t ready, and society wasn’t ready.”
When Sternberg described his meetings to Doudna, he told her that Buchman had “a Promethean glint in her eye.” Later, he used that phrase in a book he wrote with Doudna, which infuriated Buchman. Had the Happy Healthy Baby pitch occurred a few years earlier, Doudna and Sternberg wrote, they would have dismissed the idea “as pure fantasy” because “there was little chance of anyone pursuing such Frankenstein schemes.” But the invention of CRISPR-Cas9 technology had changed that. “Now, we could no longer laugh off this kind of speculation. Making the human genome as easily manipulable as that of a bacterium was, after all, precisely what CRISPR had accomplished.”4
Napa, January 2015
As a result of her Hitler dream and Sternberg’s Happy Healthy Baby story, Doudna decided in the spring of 2014 to become more engaged in the policy discussions about how CRISPR gene-editing tools should be used. At first she considered writing an op-ed for a newspaper, but that did not seem adequate to the challenge. So she harked back forty years earlier to the process that led to the February 1975 Asilomar conference, the one that had come up with the “prudent path forward” guidelines for work on recombinant DNA. She decided that the invention of CRISPR gene-editing tools warranted convening a similar group.
Her first step was to enlist the participation of two of the key organizers of the 1975 Asilomar conference: Paul Berg, who had invented recombinant DNA, and David Baltimore, who had been involved in most of the major policy gatherings, beginning with Asilomar. “I felt that if we could get them both we would have a direct link to Asilomar and a stamp of credibility,” she recalls.
Both agreed to participate, and the meeting was set for January 2015 at a resort in Napa Valley about an hour north of San Francisco. Eighteen other top researchers were invited, including Martin Jinek and Sam Sternberg from Doudna’s lab. The focus would be on the ethics of making inheritable genetic edits.
At Asilomar the discussions had been mostly about safety, but Doudna made sure that the Napa conference tackled the moral questions: Did the premium that America put on individual liberty require that decisions about gene-editing of babies be left mainly to parents? To what extent would creating gene-edited babies—and abandoning the idea that our genetic endowments came from a random natural lottery—undermine our sense of moral empathy? Was there a danger in decreasing the diversity of the human species? Or, to frame the question from a more bioliberal perspective: If the technology was available to make healthier and better babies, would it be ethically wrong not to use it?5
A consensus quickly developed that it would be bad to completely ban germline gene editing. The participants wanted to leave the door open. Their objective became similar to that of Asilomar: finding a path forward rather than putting on the brakes. That would become the theme of most subsequent commissions and conferences organized by scientists: it was too early to do germline editing safely, but someday it would happen, and the goal should be to provide prudent guidelines.
