The wrong way to make policy about heritable genome modification

The wrong way to make policy about heritable genome modification
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Last fall, when a Chinese scientist announced that he had created genetically modified twin babies, the world was stunned and outraged. In the U.S., we were able to draw some modicum of reassurance from a policy that has served as a barrier to such reckless human experimentation: A rider to the federal spending bill bars the Food and Drug Administration (FDA) from considering clinical trials “in which a human embryo is intentionally created or modified to include a heritable genetic modification.”

Yet now that provision is being eyed for removal.


When it was adopted in 2015, the provision brought the U.S. into closer alignment with most other countries across the globe with developed biotech sectors. During the late 1990s and early 2000s, dozens of national legislatures debated whether new genetic technologies should be used to alter the biology and traits of future human beings.

Every one of them decided that the benefits would be dubious at best and the societal dangers unacceptably dire, and passed laws against it. In Europe, 29 countries also signed and ratified the Convention on Human Rights and Biomedicine, a binding international treaty that puts human germline modification off limits. These policy decisions were motivated in large part by concerns that heritable genome modification would exacerbate inequality and discrimination, and enable a new market-based eugenics.

At the time, our elected representatives in the U.S. didn’t really engage these questions. Rider notwithstanding, they have still not seriously deliberated the social, ethical, and policy issues at stake.  

To be sure, slipping a provision into a massive budget bill without thorough debate is a decidedly suboptimal way to craft policy, especially about such a profoundly consequential matter. But so is precipitously removing or altering it. To do this now, after the “CRISPR babies,” would greatly compound the problem: It could easily be seen as a signal that Congress is uninterested in open deliberations about whether to move toward altering the genes and traits of future children and generations.

There is no pressing need for this move. The rider affects neither ongoing work to develop gene therapies for existing patients, nor genetic research on human embryos. The stated motivation for abandoning it is to allow the FDA to consider clinical trials of a technique that involves combining the genetic material of three people into a single embryo.

In one variation, the nucleus of a woman’s egg is transferred into an egg provided by another woman from which the nucleus has been removed; the patched-together egg is then fertilized to become a “three-person embryo.” The technically accurate term for this procedure is “nuclear genome transfer.” While different from heritable genome editing with CRISPR or other tools in that it does not alter nuclear genes, it is a form of heritable genome modification.

Just one country in the world has explicitly approved clinical use of nuclear genome transfer. In 2015, the UK legalized it for the small number of women with a rare form of mitochondrial disease who want a (mostly) genetically related child who is (hopefully) not affected by the condition. Even this limited decision, made after years of public and Parliamentary debate, was highly controversial.

Among the prominent issues: the argument for the technique’s medical necessity is shaky since alternatives exist; the risks to any resulting children are significant; and the likelihood that allowing heritable mitochondrial changes will be leveraged to open the door to all heritable modifications is great.

Concerns about risks to children who would develop from three-person embryos — and to their offspring — have not been assuaged by preclinical or animal studies. One persisting worry is that dysfunctional mitochondrial DNA carried over into the resulting children would produce “mitochondrial heteroplasmy” that could trigger serious health problems at any point during life. Another is that the mismatch between nuclear and mitochondrial genes introduced by nuclear genome transfer would lead to incompatibilities in biological interactions necessary for healthy cell functioning. A new red flag about this prospect was raised this month by a human population study in Science.

While concerns about safety risks and lack of medical need remain salient, worries about facilitating all forms of germline modification have deepened. One reason is the mission creep that’s already occurred: There have been about a half dozen births from three-person embryos, but the technique has been used only once as an effort to prevent mtDNA disease in the resulting child.


The other procedures targeted infertility, despite the lack of compelling evidence connecting it to mitochondrial dysfunction. It’s clear to all that the potential financial gains of commercializing nuclear genome transfer for infertility would be huge — as would selling genetic “upgrades” via embryo editing to wealthy parents. With so much fortune and fame in the mix, we cannot leave these decisions to self-interested parties.

Worrying is the short step from babies created from three-person embryos to CRISPR babies —literally.  The same people in the same laboratories, including Dieter Egli of Columbia University and Shoukhrat Mitalipov of Oregon Health and Science University, are working on both forms of heritable genome manipulation. John Zhang, the fertility doctor who secretly used nuclear genome transfer in Mexico to evade U.S. rules, openly endorses a future in which “parents can select hair or eye color, or maybe improve their children’s IQ.” With regard to nuclear genome transfer he says, “Everything we do is a step toward designer babies.”

Each of those steps takes us closer to the edge of a treacherous cliff, and some seem eager to give us a shove. It’s time to step back from the brink, and to deliberate carefully and collectively about whether the future to which we aspire should include any form of heritable genome modification. Until then, the law of the land should keep the door closed on clinical uses of these techniques. Otherwise individual scientists will race ahead, and it will be too late for us to decide.

Marcy Darnovsky, Ph.D., is the executive director of the Center for Genetics and Society.