Take No for an Answer on Genetic Engineering

This year may be a turning point for genetic engineering. Ever since the discovery in 2012 of a technique for editing genomes, there has been intense interest in how it might unleash medical marvels — or eugenic nightmares.

So far, both the hopes and the worries around this technology, called CRISPR-Cas9, have been largely theoretical. But in 2023, medical companies began the FDA approval process for what could become the first gene therapies in human beings, targeting sickle cell disease and beta thalassemia, two blood disorders.

Hanging over the promise of such therapies, however, is the persistent worry that the same technology that would at first be used to treat genetic diseases one patient at a time would eventually be used to manipulate the human species. The therapies that are now being considered will treat living patients with an illness caused by a genetic defect they inherited, but it will not pass the genetic modification along to the patients’ children.

But CRISPR could indeed be used in this way, altering the human germline. Its use could also expand from medical therapy to human enhancement — to picking your child’s hair color or height, or, in theory, to engineering them to be genetically competitive mates or Harvard applicants or supersoldiers. The enormous power that this could grant the living over the yet-to-be-born raises profound ethical fears: of designer babies, a Gattaca future, a new eugenic era created by nefarious tyrants or well-meaning parents.

Often it has seemed that it is genetic researchers themselves who are most haunted by the potential misuse of the power they are unleashing. Jennifer Doudna, one of the principal inventors of CRISPR, wrote in her 2017 book A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution about a nightmare she once had. At the time, Doudna had been thinking about the use of CRISPR in pigs to make their organs safer to transplant into humans. In her dream, she was asked into a meeting with a pig-faced Adolf Hitler: “Fixing his eyes on me with keen interest, he said, ‘I want to understand the uses and implications of this amazing technology you’ve developed.’”

There are two broad ways of responding to these developments. In one camp we have practitioners like Doudna, along with mainstream ethicists. To avoid nightmare scenarios of rogue actors sullying the field, for years they have been holding summits and conventions discussing where the ethical boundaries may be. Their ostensible purpose is to find a broad social consensus around whether applications like germline engineering should be allowed.

In the other camp we have more committed skeptics, who have not been wrought with such doubt. For decades, long before any of this was yet technically possible, critics of biotechnology such as Leon Kass and the late Paul Ramsey have argued that, while genetic therapy for existing, living patients raises few ethical problems, heritable modification of the human germline should simply be prohibited. In a 1971 Science article, Kass warned that engineering of future generations would more likely be used for eugenic than therapeutic ends and called for “caution, restraint, delay, abstention” in the development of such techniques: “When we lack sufficient wisdom to do, wisdom consists in not doing.”

The debate around genetic engineering, then, is stuck in an odd configuration. The mainstream ethical camp is consumed with agonized soul-searching over the need for democratic oversight — but in practice what they achieve is endlessly open-ended discussion that delays any particular call to action. Meanwhile, as the technology for making designer babies keeps advancing while endless conferences don’t seem all that interested in stopping it, Kassian skeptics might easily despair that they have not been heard.

But they have been heard. While scientists and ethicists were busy talking, governments across the world have outlawed human germline engineering. This does not mean the practice will remain prohibited forever — laws can change — but it does mean that we already have a political consensus.

It’s time, then, to stop scratching our chins about the ideal parameters we might put in place around gene editing and start anchoring the debate about the ones we already have.

While 2023 may be a turning point for gene therapy innovation, we can look back to 2015 as a turning point for American gene therapy governance. That was the year that our country resolved critical questions about how it would approach the ethical and political questions raised by human gene editing.

That year, scientists in China reported the first use of CRISPR to modify genes in human embryos. The embryos they used in that experiment were nonviable, but many felt that an ethical boundary had been crossed. In the United States, the news was met by two different responses, which neatly represent the two broad approaches to governing this kind of technology.

Leading one of these approaches were scientists at the forefront of CRISPR research, who organized an International Summit on Human Gene Editing in Washington, D.C. at the end of the year. The summit included not only cutting-edge researchers but also ethicists like Françoise Baylis, who has been highly critical of heritable gene editing. Also present were David Baltimore and Paul Berg, eminent in biology for convening the 1975 Asilomar Convention on Recombinant DNA, when geneticists put a pause on the then-nascent biotech field to discuss its risks and how to manage them. At the 2015 summit, speakers reported on the promise of the technology, on its dangers, and on the ethical, political, and social quandaries it posed. Seminars were held, journalists reported on the proceedings, and there were plenty of thoughtful discussions of the uses and implications of this amazing technology.

Shortly after the summit, the organizing committee released a brief statement in which it took a position on heritable genetic modifications of human embryos that can generously be described as tentative:

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.

Since that summit, the same group convened two additional meetings, one in Hong Kong in 2018 and another just this past March in London. The 2018 summit closely followed the announcement that twin girls whose genes had been edited at the embryonic stage had recently been born in China, a development the summit’s organizers strongly condemned. Nevertheless, after the 2018 meetings, they expressed optimism that heritable genetic modifications could eventually become an acceptable part of medicine:

Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials [of germline editing].

The most recent summit carried on with this tentative approach, with the organizers still noting that “societal discussion and policy debate” have not “been concluded,” and that “at this time” heritable gene editing does not yet meet the conditions of safety, efficacy, legality, and transparent oversight.

Reading these statements, one might think that the organizers deserve some credit for taking a cautious approach to heritable gene editing and conducting so much thoughtful discussion before jumping into the use of a novel technology. Their self-restraint might seem particularly admirable in comparison to the way reproductive technologies like in vitro fertilization and surrogacy were rushed along in previous decades without much public deliberation.

But the crucial difference is that for heritable gene editing, we have already had a societal discussion and policy debate and reached the conclusion that it should not be done. As of 2020, seventy countries, including the United States, have passed laws restricting or outright prohibiting heritable gene editing of embryos.

In contrast to the erudite but idle work of these commissions, we can look back to 2015 at a very different response to the questions raised by heritable gene editing. In June of that year, Congress introduced a measure effectively prohibiting heritable gene editing in the United States.

The law is a bit of a kludge. Rather than a freestanding piece of legislation, it became part of the 2016 appropriations bill and has since been renewed in subsequent appropriations bills. Furthermore, it does not directly prohibit the technology; instead, it bans the Food and Drug Administration from spending money to consider applications to begin trials of heritable gene editing in humans. This means that privately funded research on germline engineering is not prohibited, but a clinical trial and marketing of any therapy is effectively prohibited because it would require FDA approval, and thus federal funds.

Here’s the full text of the law, buried in the most recent 1,600-page annual appropriations bill:

None of the funds made available by this Act may be used to notify a sponsor or otherwise acknowledge receipt of a submission for an exemption for investigational use of a drug or biological product under section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)) or section 351(a)(3) of the Public Health Service Act (42 U.S.C. 262(a)(3)) in research in which a human embryo is intentionally created or modified to include a heritable genetic modification. Any such submission shall be deemed to have not been received by the Secretary, and the exemption may not go into effect.

Compare this to, say, Germany’s 1990 Embryo Protection Act, which straightforwardly promises punishment to those who would manipulate human genes:

Anyone who artificially alters the genetic information of a human germ line cell will be punished with imprisonment up to five years or a fine.

The American law isn’t even directed at doctors who perform gene editing on embryos, but rather at the budget process for the FDA. So what punishment would be in store for the person who conducts a clinical trial of a heritable gene-editing therapy, or tries to sell the procedure, without first acquiring FDA approval? It’s simple: just turn to the Federal Food, Drug, and Cosmetic Act at 21 U.S.C. 333(a) to find out.

Related to the roundabout way this law prohibits gene editing is its status as an appropriations rider rather than a freestanding piece of legislation. Tacking such measures onto budget bills is an inelegant way to legislate, especially on morally serious subjects like whether to permit human genetic engineering. And yet, such riders are an enduring feature of American governance.

Consider the 1995 Dickey–Wicker Amendment, which prohibits federal funding for the creation and destruction of human embryos for research purposes. The closely related issue of whether federal funding may be used for research on embryonic stem cells was one of the major controversies of President George W. Bush’s administration, with the president favoring a more restrictive approach than did Democrats in Congress. But even though Congress twice passed legislation to liberalize funding for embryonic stem cell research (with Bush vetoing both bills), the Dickey–Wicker Amendment was untouched and has remained in place to this day.

The 2015 appropriations rider that bans heritable genetic modifications was challenged in 2019 and nearly removed. Fertility industry lobbyists tried to convince Democratic legislators in the House to overturn the prohibition. (At that time, the industry was not interested in using CRISPR on embryos but in carrying out a different procedure to create children with three genetic parents to prevent the inheritance of certain mitochondrial diseases.) As a 2019 Science magazine piece reported, “some scientific advocacy groups dislike the FDA bill language because it means Congress made the decision, not scientific and regulatory experts.” The piece goes on to quote the American Society for Reproductive Medicine’s chief lobbyist, who dismisses the law as “an antiscience rider” that should be removed to allow “the FDA to do its job.”

After further negotiations, however, the rider was restored to the appropriations bill by a nearly unanimous vote of the House Appropriations Committee. Lawmakers on both sides of the aisle, however, acknowledged the “need to address the issue comprehensively, rather than have it debated annually during the appropriations process,” as Science magazine put it.

This is good news for all concerned — or should be. Friends of a human future can recognize that they already enjoy the status quo, and confidently defend it. Meanwhile, scientists and ethicists, who claim to be agonizing over the need for democratic deliberation on genetic engineering, can recognize that democracy has already decided, and stop agonizing.

Yes, a more permanent and straightforward prohibition on germline engineering would be preferable to the kludgy and potentially unstable appropriations rider. But a comprehensive, deeply thoughtful discussion of the issues in Congress may not be what’s needed to achieve this. We can see that the endless thoughtfulness of the International Summit on Human Gene Editing has resulted not in a clear answer to the questions raised by this technology but rather in rationalizations of its various uses.

Of course, some scientists do believe that heritable gene editing should be done one day if it becomes technically safe and effective. That’s the position outlined by Jennifer Doudna, a CRISPR inventor and organizer of the summit, in A Crack in Creation, where she writes that she does not “believe there’s an ethical defense for banning germline modification outright.” But the series of summits on gene editing convened by Doudna and others have not candidly argued in favor of this position — that germline engineering should be allowed. They have instead hidden behind calls for widespread societal discussion and debate of moral quandaries.

But since the current policy consensus on heritable gene editing is that the practice is not permitted, calls for thoughtful debates about such policy will tend to point in one direction: not toward the enactment of new restrictions but the loosening of existing ones. For all the intellectual sophistication with which these summits have raised ethical, political, and medical questions, they have done so with what Paul Ramsey condemned as a “frivolous conscience” — seeing moral discourse not as a way of deciding what should or should not be done, but as a way of constructing rationalizations for eventually doing what science makes possible.

In contrast, to have a serious conscience “means to say in raising urgent ethical questions that there may be some things that men should never do. The good things that men do can be made complete only by the things they refuse to do.” If we were to say yes to germline engineering, we would surely need to qualify that answer with a thousand and one conditions and reservations to specify when, where, by whom, and how it could be done. But by responding to this problem with a serious conscience, we can simply let our no be no.