The code breaker, p.30
The Code Breaker, page 30
As it turned out, the political and public reaction to the CRISPR babies was in line with Andy’s. Two weeks after returning from Hong Kong, Doudna attended that meeting on Capitol Hill with eight senators to discuss gene editing. Such meetings are usually a forum for politicians to express their shock and dismay about something they don’t fully understand and then call for more laws and regulations. Quite the opposite occurred at the Senate briefing, which was hosted by Illinois Democrat Dick Durbin and included South Carolina Republican Lindsey Graham, Rhode Island Democrat Jack Reed, Tennessee Republican Lamar Alexander, and Louisiana Republican Bill Cassidy (a doctor). “I was pleased that all of those senators, all of them, were encouraging of the general idea of editing as an important technology,” Doudna says. “I was surprised none of them were demanding more regulations. They just wanted to figure out, ‘Where do we go from here?’ ”
Doudna and National Institutes of Health director Francis Collins, who accompanied her, explained that there were already regulations in place to restrict the use of gene editing in embryos. The senators were more interested in trying to understand the value CRISPR might have in medicine and agriculture. Rather than focus on the just-born Chinese CRISPR babies, they asked detailed questions about how CRISPR might work, both in somatic therapies and germline editing, to cure sickle-cell anemia. “They were electrified by the sickle-cell potential, and for other debilitating single-gene diseases such as Huntington’s and Tay-Sachs,” Doudna recalls. “They talked about what it meant for sustainable health care.”5
* * *
Two international commissions were created to deal with the issue of germline editing. The first was organized by the national science academies that had been part of the process since 2015. The other was convened by the World Health Organization. Doudna feared that having two groups might lead to conflicting messages, thus allowing future He Jiankuis to make their own interpretations of the guidelines. So I met with Victor Dzau, president of the U.S. National Academy of Medicine, and Margaret Hamburg, co-chair of the WHO commission, to see how they would divide up responsibility. “The national academies group is focusing on science,” Hamburg said. “The WHO is looking at how to create a global regulatory framework.” Even though there will be two reports, Dzau said, it will be better than in the past, when the scientific academies in different countries were creating different guidelines.
Nevertheless, Hamburg conceded that this was unlikely to prevent countries from crafting their own rules. “They have different attitudes and regulatory standards, like they do on genetically modified foods, that reflect their different social values,” she explained. That could, unfortunately, lead to genetic tourism. Privileged people who want enhancements will travel to the countries that offer them. She acknowledged that it would be hard for the WHO to police compliance: “This is not like nuclear weapons where you can have guards and padlocks to enforce a security regimen.”6
The moratorium issue
As the two commissions were getting to work in mid-2019, a public dispute erupted in the scientific community that once again pitted Doudna against the Broad Institute’s hard-charging Eric Lander. It was over the use of the word “moratorium,” which most scientific committees over the years had avoided.
In some ways the dispute over whether to call for an official moratorium was semantic. The conditions that had been specified for permissible embryo gene editing—that it be safe and “medically necessary”—could not be met for the time being. But some argued that Jiankui’s actions showed the need for a clearer and brighter stoplight. Among them were Lander, his protégé Feng Zhang, Paul Berg, Francis Collins, and Doudna’s scientific collaborator Emmanuelle Charpentier. “If you use the m-word,” Collins explained, “it has a little more clout.”7
Lander liked being a public intellectual and policy advisor. Articulate, funny, gregarious, and magnetic—at least to those not turned off by his intensity—he was very good at advocating positions and convening groups of earnest chin-strokers. But Doudna suspected that he stirred up the moratorium issue, at least in small part, because she and David Baltimore, rather than the publicity-shy Zhang, had taken the limelight as the foremost public policy thinkers about CRISPR. “Eric and the Broad Institute have a very big bullhorn,” she says. “Their call for a moratorium was a way for them to capture a lot of headlines about something they didn’t step up to the plate about early on.”
Whatever his motives (and I tend to think they were sincere), Lander set about rounding up support for an article to be published in Nature titled “Adopt a Moratorium on Heritable Genome Editing.” Zhang of course signed up, as did Doudna’s erstwhile collaborator Charpentier. So did Berg, whose recombinant DNA discoveries had prompted Asilomar forty-four years earlier. “We call for a global moratorium on all clinical uses of human germline editing—that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children,” the article began.8
Lander coordinated the essay with his friend Collins, with whom he had worked on the Human Genome Project. “We have to make the clearest possible statement that this is a path we are not ready to go down, not now, and potentially not ever,” Collins said in an interview the day the Lander article was released.
Lander emphasized that the issue should not be left to individual choice and the free market. “We’re trying to plan the world we’re going to leave for our children,” he said. “Is it a world where we’re deeply thoughtful about medical applications, and we’re using it in serious cases, or is it a world where we just have rampant commercial competition?” Zhang made the point that the issues surrounding gene editing needed to be settled by society as a whole and not by individuals. “You can imagine a situation where parents will feel pressure to edit their children because other parents are,” he said. “It could further exacerbate inequality. It could create a total mess in society.”9
* * *
“Why is Eric so intent on publicly pushing for a moratorium?” Margaret Hamburg, the co-chair of the World Health Organization group, asked me. It was a sincere question. Lander’s reputation was such that even when he did something that seemed straightforward, others suspected his motives. The call for a moratorium, she felt, seemed like showboating; it was unnecessary, since both the WHO and the national academies were already embarked on figuring out proper guidelines rather than calling a halt to germline editing.10
Baltimore too expressed puzzlement. Lander had tried to recruit him to sign the letter, but as with the discussion of recombinant DNA forty years earlier at Asilomar, Baltimore was more interested in finding “a prudent path forward” for what could be a lifesaving advance rather than declaring a moratorium that may be difficult to lift once in place. He suspected that Lander might be pushing the moratorium to curry favor with Collins, the director of the National Institutes of Health, which provides a lot of funding for academic labs.
As for Doudna, her opposition to a moratorium became stronger the more that Lander pushed it. “Since germline editing has already been done with the Chinese babies, I think to put out a call for a moratorium at this stage is just unrealistic,” she says. “If you call for a moratorium, you effectively take yourself out of the conversation.”11
Doudna’s view prevailed. In September 2020, a two-hundred-page report was issued by the international academies of science commission formed after Jiankui’s shocking announcement. It did not call for a moratorium, nor mention that word, even though Lander was one of the eighteen commission members. Instead, it said that heritable human genome editing “might in the future provide a reproductive option” for couples who have genetic diseases. The report noted that making inheritable gene edits was not yet safe and usually not medically necessary, but it came down in favor of “defining a responsible pathway for clinical use of heritable human genome editing”—in other words, continuing to pursue the goal of “a prudent path forward” that was endorsed at the January 2015 Napa Valley conference that Doudna organized.12
He Jiankui convicted
Instead of being acclaimed a national hero, as he had fantasized, He Jiankui was put on trial at the end of 2019 in the People’s Court of Shenzhen. The proceedings had many elements of a fair trial: he was permitted to have his own attorneys and to speak in his own defense. But the verdict was not in doubt since he had pleaded guilty to the charge of “illegal medical practice.” He was sentenced to three years in prison, fined $430,000, and banned for life from working in reproductive science. “In order to pursue fame and profit, [he] deliberately violated the relevant national regulations and crossed the bottom lines of scientific and medical ethics,” the court declared.13
The official Chinese news report on the trial also revealed that a third CRISPR baby engineered by Jiankui had been born to a second woman. There were no details about the baby nor about the current status of Lulu and Nana, the original CRISPR-edited twins.
When Doudna was asked by the Wall Street Journal to comment on the conviction, she was careful to criticize Jiankui’s work but not to denounce germline gene editing. The scientific community would have to sort out the safety and ethical issues, she said. “To me, the big question is not will this ever be done again,” she said. “I think the answer is yes. The question is when, and the question is how.”14
PART SEVEN The Moral Questions
If scientists don’t play God, who will?
—James Watson, to Britain’s Parliamentary and Scientific Committee, May 16, 2000
CHAPTER 40 Red Lines
The stakes
When He Jiankui produced the world’s first CRISPR babies, with the goal of making them and their descendants immune to an attack by a deadly virus, most responsible scientists expressed outrage. His actions were deemed to be at best premature and at worst abhorrent. But in the wake of the 2020 coronavirus pandemic, the idea of editing our genes to make us immune to virus attacks began to seem a bit less appalling and a bit more appealing. The calls for a moratorium on germline gene editing receded. Just as bacteria have spent millennia evolving ways to develop immunity to viruses, perhaps we humans should use our ingenuity to do the same.
If we could safely edit genes to make our children less susceptible to HIV or coronaviruses, would it be wrong to do so? Or would it be wrong not to do so? And what about gene edits for other fixes and enhancements that might be possible in the next few decades? If they turn out to be safe, should governments prevent us from using them?1
The issue is one of the most profound we humans have ever faced. For the first time in the evolution of life on this planet, a species has developed the capacity to edit its own genetic makeup. That offers the potential of wondrous benefits, including the elimination of many deadly diseases and debilitating abnormalities. And it will someday offer both the promise and the peril of allowing us, or some of us, to boost our bodies and enhance our babies to have better muscles, minds, memory, and moods.
In the upcoming decades, as we gain more power to hack our own evolution, we will have to wrestle with deep moral and spiritual questions: Is there an inherent goodness to nature? Is there a virtue that arises from accepting what is gifted to us? Does empathy depend on believing that but for the grace of God, or the randomness of the natural lottery, we could have been born with a different set of endowments? Will an emphasis on personal liberty turn the most fundamental aspects of human nature into consumer choices made at a genetic supermarket? Should the rich be able to buy the best genes? Should we leave such decisions to individual choice, or should society come to some consensus about what it will allow?
Then again, are we getting a bit overdramatic with all of this handwringing? Why in the world would we not seize the benefits that will come from ridding our species of dangerous diseases and enhancing the capacities of our children?2
The germline as a red line
The primary concern is germline editing, those changes that are done in the DNA of human eggs or sperm or early-stage embryos so that every cell in the resulting children—and all of their descendants—will carry the edited trait. There has already been, and rightly so, general acceptance of what is known as somatic editing, the changes that are made in targeted cells of a living patient and do not affect reproductive cells. If something goes wrong in one of these therapies, it can be disastrous for the patient but not for the species.
Somatic editing can be used on certain types of cells, such as those of the blood, muscles, and eyes. But it is expensive, doesn’t work on all cells, and may not be permanent. Germline edits could make a fix in all of the cells of the body. Thus it holds a lot more promise. And a lot more perceived peril.
Until the creation of the first CRISPR babies in 2018, there were two main medical methods for selecting the genetic traits of a child. The first was prenatal testing, which involves performing genetic tests on embryos as they are growing in the womb. Nowadays, such tests can detect Down’s syndrome, sex, and dozens of congenital conditions. Parents can decide to abort the embryo if they don’t like the traits. In the U.S., a prenatal diagnosis of Down’s syndrome results in an abortion approximately two-thirds of the time.3
The development of in vitro fertilization led to another advance in genetic control: preimplantation genetic diagnosis. Couples can, if they are able, produce multiple fertilized eggs and have them tested in a lab dish, before they get implanted, for genetic characteristics. Do they have the mutations for Huntington’s or sickle cell or Tay-Sachs? Or someday we can ask, as happens in the movie Gattaca, do they have the desired genes for height, memory, and muscle mass? With preimplantation diagnosis, those fertilized eggs with the parents’ desired traits can be implanted and the rest discarded.
Both of these techniques raise some of the same moral issues as germline gene editing. For example, James Watson, the outspoken co-discoverer of DNA, once opined that a woman should have the right to abort a fetus based on any preference or prejudice, including not wanting a child that would be short or dyslexic or gay or female.4 This caused a lot of people to recoil, understandably. Nevertheless, preimplantation genetic diagnosis is now considered morally acceptable, and parents are generally free to make their own choices about what criteria to use.
The question is whether germline gene editing will someday be considered just another in a long continuum of once controversial biological interventions, such as prenatal or preimplantation screening, that have gradually been accepted. If so, does it make sense to treat germline editing as something distinct, subject to a different set of moral standards?
Call this the continuum conundrum. There are ethicists who are good at making distinctions and those who are good at debunking distinctions. Or to put it another way, there are ethicists who discern lines and others who blur them. The ones who like to blur the lines often go on to pronounce that the lines are so blurry there is no rationale for treating the categories differently.
Take the atom bomb, as an analogy. When Secretary of War Henry Stimson was wrestling with whether to drop it on Japan, some argued that it was an entirely new category of weapon, a line that should not be crossed. Others said it was not fundamentally different, and indeed might be less brutal, than the massive firebombing campaigns that had been waged on Dresden and Tokyo. The latter side prevailed, and the bomb was dropped. Later, however, atomic weaponry came to be seen as being in a distinct category, and it hasn’t been used since.
In the case of gene editing, I think the germline is indeed a real line. There may not be a razor-sharp line differentiating it from other biotechnologies, but as Leonardo da Vinci taught us with his sfumato, even slightly blurry lines can be definitive. Crossing the germline takes us to a distinct new realm. It involves engineering a genome rather than nurturing one that was produced naturally, and it introduces a change that will be inherited by all future descendants.
Nevertheless, this doesn’t mean the germline should never be crossed. It simply means that we can view the germline as a firebreak that gives us a chance to pause, if we decide we ought to, the advance of genetic engineering techniques. The question becomes: Which cases, if any, should cause us to cross this germline?
Treatment vs. enhancement
Another line we might consider, in addition to that between somatic and germline editing, involves the distinction between “treatments” designed to fix dangerous genetic abnormalities and “enhancements” designed to improve human capacities or traits. At first glance, treatments seem easier to justify than enhancements.
But the treatment-vs.-enhancement distinction is a blurry one. Genes might predispose or predetermine certain kids to be short or obese or have attention deficits or be depressive. At what point do genetic modifications to fix such traits cross the line from health treatment to enhancement? What about genetic modifications that help prevent a person from getting HIV or coronavirus or cancer or Alzheimer’s? Perhaps for these we need a third category called “preventions” in addition to the ill-defined “treatments” and “enhancements.” And to those we might even add a fourth category, called “super-enhancements,” which would include giving humans new capabilities that the species has not had before, such as the ability to see infrared light or hear super-high frequencies or avoid the bone, muscle, and memory loss that comes with age.
As you can see, the categories can get complex, and they don’t necessarily correlate with what might be desirable and ethical. In order to chart our way through this moral minefield, it may be useful to do some thought experiments.
