The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

by Walter Isaacson

Congress passed a provision barring the Food and Drug Administration from reviewing any treatment “in which a human embryo is intentionally created or modified to include a heritable genetic modification.”

Barack Obama’s science advisor, John Holdren, declared, “The Administration believes that altering the human germline for clinical purposes is a line that should not be crossed at this time,” and the director of the National Institutes of Health, Francis Collins, announced, “The NIH will not fund any use of gene-editing technologies in human embryos.”

Britain, likewise, the editing of human embryos was restricted by various regulations. But in neither Britain nor the U.S. was there an absolute and...

Russia, there were no laws to prevent the use of gene editing in humans, and President Vladimir Putin in 2017...

early 2018, he began to discuss the possibility of not only reading human genomes but also editing them. “For billions of years, life progressed according to Darwin’s theory of evolution: random mutation in DNA, selection and reproduction,” he wrote on his website. “Today, genome sequencing and genome editing provide powerful new tools to control evolution.” His goal, he said, was to sequence a human genome for $100, then move on to fixing any problems. “Once the genetic sequence is known, we can use CRISPR-Cas9 to insert, edit or delete the associated gene for a particular trait. By correcting the disease genes, we humans can better live in the fast changing environment.”

“I support gene editing for the treatment and prevention of disease,” Jiankui wrote in a post on the social media site WeChat, “but not for enhancement or improving I.Q., which is not beneficial to society.”9

the Templeton Foundation, which supports the study of big ethical questions, had provided funding for a series of discussions on CRISPR.

What struck Doudna and others at the meeting was that Jiankui did not seem interested in the moral issues involved with making inheritable gene edits to embryos.14

Four months earlier, he had submitted a medical ethics application to Shenzhen’s Harmonicare Women and Children’s Hospital. “We plan to use CRISPR-Cas9 to edit the embryo,” he wrote. “The edited embryos will be transferred to women and pregnancy will follow.” His goal was to allow couples who suffered from AIDS to have babies who would be protected from the HIV virus, as would all of their descendants.

it did offer Jiankui the possibility, or at least he thought so, of achieving a major historical breakthrough and enhancing the glory of Chinese science. “This is going to be a great science and medicine achievement,” he wrote in his application, comparing it to “the IVF technology which was awarded the Nobel Prize in 2010.” The hospital ethics committee gave its consent unanimously.

There are approximately 1.25 million HIV-positive people in China, a number that is still growing rapidly, and ostracism of victims is widespread.

Jiankui’s process involved taking sperm from the father, washing the cells to rid them of the HIV virus, and then injecting the sperm into the mother’s eggs. This was probably enough to ensure that the resulting fertilized eggs were free of HIV. But his goal was to guarantee that the children would never later be infected. So he injected the fertilized eggs with CRISPR-Cas9 that targeted the CCR5 gene. They were allowed to grow for five or so days in a Petri dish until they were an early-stage embryo more than two hundred cells large, and then their DNA was sequenced to see if the edits had worked.

During his visits to the U.S. in 2017, Jiankui began hinting at his plans to a few of the American researchers he met, many of whom later expressed regret that they did not try harder to stop him or blow the whistle. Most notably, he confided in William Hurlbut, a neurobiologist and bioethicist at Stanford, who had co-organized the January 2017 Berkeley gathering with Doudna. They had, Hurlbut later told the journal Stat, “several long conversations, like four or five hours long, about science and ethics.” Hurlbut realized that Jiankui was intent on making embryo edits leading to live births. “I tried to give him a sense of the practical and moral implications,” he says, but Jiankui insisted that only “a fringe group” opposed making germline edits. If such edits could be used to avoid a dread disease, Jiankui asked, why would people be against it? Hurlbut viewed Jiankui as “a well-meaning person who wants his efforts to count for good” but who was spurred by a scientific culture “that puts a premium on provocative research, celebrity, national scientific competitiveness, and firsts.”

After an investigation, Stanford cleared Quake, as well as Hurlbut and Porteus, of any wrongdoing.

Jiankui listed five principles that should be followed when deciding whether to edit human embryos: Mercy for families in need: For a few families, early gene surgery may be the only viable way to heal a heritable disease and save a child from a lifetime of suffering.… Only for serious disease, never vanity: Gene surgery is a serious medical procedure that should never be used for aesthetics, enhancement, or sex selection.… Respect a child’s autonomy: A life is more than our physical body.… Genes do not define you: Our DNA does not predetermine our purpose or what we could achieve. We flourish from our own hard work, nutrition, and support from society and our loved ones.… Everyone deserves freedom from genetic disease: Wealth should not determine health.25

Duke professor Allen Buchanan was the staff philosopher for President Reagan’s Commission on Medical Ethics, was on the Advisory Council for the National Human Genome Research Institute under President Clinton, and is a fellow of the prestigious Hastings Center. Seven years before Jiankui decided to edit the CCR5 gene in human embryos, Buchanan had supported the concept in his influential book Better Than Human: Suppose we learn that some desirable gene or set of genes already exists, but only in a small number of humans. This is precisely the situation for genes that confer resistance to certain strains of HIV-AIDS. If we rely on the “wisdom of nature” or “let nature take its course,” this beneficial genotype may or may not spread through the human population.… Suppose it were possible to ensure that such beneficial genes spread much more quickly by intentional genetic modification. This could occur by injecting genes into the testicles or, more radically, by inserting them into a large number of human embryos, utilizing in vitro fertilization. We would get the benefits… without the carnage.26

He also made a distinction between curing disease and making enhancements. “Gene surgery should only be used for treating serious disease. We should not use it for increasing I.Q., improving sports performance or changing skin color. That’s not love.”27

She ended up giving birth, after a caesarean section, to two apparently healthy girls, who were named Nana and Lulu.

Buried in Jiankui’s unpublished paper were some disturbing pieces of information. In Lulu, only one of the two relevant chromosomes had been properly modified. “We confirmed Nana’s CCR5 gene was edited successfully with frameshift mutations on both alleles and Lulu’s was heterozygous,” he admitted. In other words, Lulu had different gene versions on her two chromosomes, which meant that her system would still produce some of the CCR5 protein.

In addition, there was evidence that some unwanted off-target edits had been made and also that both embryos had been mosaics, meaning there had been enough cell division before the CRISPR editing was done that some of the resulting cells in the babies were unedited. Despite all of this, Jiankui later said, the parents chose to have both embryos implanted. Kiran Musunuru of the University of Pennsylvania later commented, “The first attempt to hack the code of life and, ostensibly, improve the health of human babies had in fact been a hack job.”

The question that she and the other organizers faced was whether they were partly to blame. For years they had been crafting criteria that should be met before there was any editing of humans. But they had stopped short of calling clearly for a moratorium or prescribing a clear process for approval of a trial. Jiankui could claim, as he did, that in his own mind he had followed these criteria.

“The sense at the meeting was that the technology had advanced to the stage where we need to have a clear pathway to clinical use of gene editing in embryos,” Doudna says. In other words, instead of trying to stop any further uses of CRISPR to make gene-edited babies, she wanted to pave the way to making it safer to do so. “To put your head in the sand or say we need a moratorium is just not realistic,” she argues. “Instead we should say, ‘If you want to move into the clinic with gene editing, these are the specific steps that need to be taken.’ ”

So the statement that Doudna, Baltimore, and the other organizers crafted was very restrained. “At this summit we heard an unexpected and deeply disturbing claim that human embryos had been edited and implanted, resulting in a pregnancy and the birth of twins,” they wrote. “The procedure was irresponsible and failed to conform with international norms.” But there was no call for a ban or moratorium. Instead, the statement simply said that the safety risks were currently too great to permit germline editing “at this time.” It then proceeded to stress, “Germline genome editing could become acceptable in the future if these risks are addressed and if a number of additional criteria are met.” The germline was no longer a red line.

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?’ ”

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.

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.”

“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.

Zhang made the point that the issues surrounding gene editing needed to be settled by society as a whole and not by individuals.

As for Doudna, her opposition to a moratorium became stronger the more that Lander pushed it.

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.

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?

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?

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.

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.

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?

Well, as with many such genes, there’s a complexity. People who get a copy of the gene from only one parent do not develop the disease, but they do develop immunity to most forms of malaria. In other words, the gene was (and in some places still is) useful, especially in sub-Saharan Africa.

genes may play multiple roles and have evolutionary reasons for existing.

2019 documentary about CRISPR, Human Nature,

“But I think that should be up to the kid later.” Asked why, he reflected for a moment and then continued slowly. “There’s a lot of things that I learned having sickle cell. Because I had it, I learned patience with everyone. I learned how just to be positive.” But would he like to have been born without sickle cell? Again, he pauses. “No, I don’t wish that I’d never had it,” he says. “I don’t think that I would be me if I didn’t have sickle cell.”

Using gene editing to prevent disabilities may make society less diverse and creative. But does this give governments the right to tell parents they can’t use such technologies?

How do we distinguish between traits that are true disabilities and ones that are disabilities mainly because society is not good at adapting for them?

DARPA already has a project going, in conjunction with Doudna’s lab, to study how to create genetically enhanced soldiers.

Two decades after the completion of the Human Genome Project, we still have little understanding of how human psychology is influenced by genetic dispositions.

At this point in our deliberations, we have to face the potential conflict between what is desired by the individual versus what is good for human civilization.

Of all the complex components that go into human intelligence, wisdom may be the most elusive. Understanding the genetic components of wisdom may require us to understand consciousness, and I suspect that’s not going to happen in this century.

On most great moral issues, there are two competing perspectives. One emphasizes individual rights, personal liberty, and a deference to personal choice. Stemming from John Locke and other Enlightenment thinkers of the seventeenth century, this tradition recognizes that people will have different beliefs about what is good for their lives, and it argues that the state should give them a lot of liberty to make their own choices, as long as they do not harm others. The contrasting perspectives are those that view justice and morality through the lens of what is best for the society and perhaps even (in the case of bioengineering and climate policy) the species. Examples include requirements that schoolkids be vaccinated and that people wear masks during a pandemic. The emphasis on societal benefits rather than individual rights can take the form of John Stuart Mill’s utilitarianism, which seeks the greatest amount of happiness in a society even if that means trampling on the liberty of some individuals. Or it can take the form of more complex social contract theories, in which moral obligations arise from the agreements we would make to form the society we want to live in.

we can see a problem with simply leaving such decisions to individual choice. A liberal or libertarian genetics of individual choice could eventually lead us—just as surely as government-controlled eugenics—to a society with less diversity and deviation from the norm. That might be pleasing to a parent, but we would end up in a society with a lot less creativity, inspiration, and edge.

Michael Sandel. If we humans find ways to rig the natural lottery and engineer the genetic endowments of our children, we will be less likely to view our traits as gifts that we accept. That would undermine the empathy that comes from our sense of “there but for the grace of God go I” toward our fellow humans who are less lucky.

the idea that germline editing was unnatural began to carry less weight for me,” she says. “I am not sure how to make a sharp distinction in medicine between what is natural and what is unnatural, and I think it’s dangerous to use that dichotomy to block something that could alleviate suffering and disability.”

Davos in January 2016, where she shared her ethical qualms about gene editing,