The U.S. must do some heavy lifting to prepare for heritable genome editing

Countries contemplating giving the green light to heritable genome editing received specific guidance from an international commission this week on how to prepare for a future in which the technology is safe and effective enough to use in human reproduction.

The commission was created in response to the news almost two years ago that a scientist in China had edited the genomes of two babies when they were single-cell embryos. (It subsequently emerged that a third baby with an edited genome had been born.)

While the scientist involved, He Jiankui, was widely condemned for conducting a premature and unethical experiment, and later fined and sentenced to jail, his first-in-humans experiment pushed the international community beyond a “germline editing — good or bad?” discussion to actively considering what it would take to justify its use.

Germline gene editing raises particular ethical and safety issues. Gene editing in a young child or adult creates changes that may affect the individual, but are not passed on to his or her children. Germline editing, also known as heritable genome editing, creates changes that are inherited by subsequent generations.

The International Commission on the Clinical Use of Human Germline Genome Editing, an expert committee co-sponsored by the U.S. National Academy of Medicine and National Academy of Sciences and the United Kingdom’s Royal Society, was specifically charged with defining a pathway to using CRISPR or other gene editing tools to modify germline cells (sperm, eggs, and their precursors) or very early-stage embryos.

The committee begins its report by stating that the technology is not yet sufficiently safe to use in humans and that, even if it were, the decision whether to permit it “must ultimately rest with individual countries.” Yet the very existence of the committee, and the nature of its recommendations, recognize the promise of this technology and that a strong case can be made for its use by prospective parents “with a known risk of transmitting a genetic disease” or “with reduced fertility.”

In the committee’s 11 thoroughly reasonable recommendations, it proposes an incremental path forward, beginning with the use of genome-editing technologies to prevent serious diseases caused by mutations in a single gene (monogenic diseases) such as Huntington’s disease, cystic fibrosis, and sickle cell disease, that cause severe morbidity or premature death.

As reasonable as the recommendations are, they will require work by interested nations to meet the commission’s proposed preconditions for using heritable human genome editing. The challenges for U.S. health and technology policy are especially significant. Here are three that will be heavy lifts for the U.S.:

1. The report recommended that countries undertake “extensive societal dialogue” before making any decision about whether to permit heritable editing. While some countries have a history of extensive public engagement around controversial new technologies like genetically modified foods, no such dialogue has been attempted in the U.S. regarding genome editing, or any other emerging technology for that matter. It is hard to imagine cost-effectively engaging large swaths of the American public on this issue or why doing so could be considered a higher priority than engaging them on other more pressing issues, such as pandemic recovery, racial justice, or political polarization.

A more modest proposal might suffice, such as targeted engagement with specific stakeholders and deliberation with a small but representative sample of the public. But even that would be departure from America’s existing approach to policy in this area, which thus far amounts to a de facto ban on heritable genome editing enacted via a budget rider first passed in 2015 whose merits were not initially publicly discussed and which has, since then, been annually re-upped with little to no debate.

2. An early emphasis in the report is that heritable editing, like other genetic technologies, should be deployed in ways that avoid bias and discrimination and “ensure equitable access.” An immediate question is how the U.S. can satisfy this precondition when it is almost entirely alone among developed nations in not providing universal access to health care?

In its recommendations about how countries should decide who merits access to heritable editing, the commission requires that prospective parents first try in vitro fertilization with preimplantation genetic diagnosis, reproductive technologies that many American health plans do not cover. If made available today, the new genetic technology the report focuses on would, like so many others, be available only to those Americans with exceptional insurance coverage or the ability to pay out of pocket. Significant changes to U.S. health policy would be needed to meet the “equitable access” recommendation for heritable genome editing.

3. The commission calls for countries to have mechanisms and regulatory bodies in place that allow for prospective and ongoing use-by-use assessment of the safety and ethics of all applications of heritable editing. The U.S. Food and Drug Administration could assess the safety and effectiveness of this technology if it was authorized to do so, and institutional review boards could protect human research subjects.

But the U.S. does not have in place a regulatory structure for governing assisted reproductive technologies like in vitro fertilization, which in countries like the United Kingdom and Australia can be adapted to accommodate heritable editing.

The American Society for Reproductive Medicine and the Society for Assisted Reproductive Technologies, professional organizations that represent fertility clinics and providers, issue guidance addressing clinical and ethical issues in fertility medicine, such as egg freezing and sex selection, and could address the use of heritable genome editing. But their guidance is voluntary and notoriously permissive, allowing procedures that other countries ban, and it is unlikely to satisfy the commission’s requirement for a national oversight system.

The report acknowledges that the world’s attention is appropriately focused today on the “twin upheavals” of the devastating Covid-19 pandemic and this summer’s urgent calls to address racial injustice and inequities. While the prospect of heritable genome editing is very different than those two pressing issues, the committee points out that it also transcends individual countries, deserves wide-ranging discussion, and raises important equity implications.

That is exactly right. And it is especially striking at this moment in U.S. history that in order to prepare for heritable editing — at least according to the recommendations of this commission — the U.S. would need to make health and technology policy changes that would democratize science policy, secure universal access to health care including fertility treatment, and create a reasonable regulatory framework for reproductive medicine. A relatively small number of Americans families with serious heritable genetic diseases are likely to seek out germline editing. Yet making the changes to U.S. policy to give them the opportunity to do that will benefit everyone.

Josephine Johnston is director of research and research scholar at the Hastings Center and co-editor of the book “Human Flourishing in an Age of Gene Editing” (Oxford University Press, 2019).