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Should We Be Worried About How Gene-Edited Kids Will Affect Future Generations?

A new international commission will consider the pros and cons of human genome editing.

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Stepanenko Oksana/Dreamstime

Genetic engineering researchers around the world are scrambling to devise some sort of rules to restrict "rogue gene-editing" of human embryos, possibly even imposing a moratorium on the practice. U.S. National Academy of Medicine chief Victor Dzau just announced at Davos that his institute will team up with similar groups in other countries to launch an international commission on the science and ethics of human genome-editing; the goal is to devise some rules to guide future research and clinical applications.

The efforts were spurred by the bombshell revelation last November that Chinese biotechnologist He Jiankui used CRISPR to edit the genomes of some embryos to cripple the CCR5 gene that is the gateway to HIV infections. Two of those embryos have now reportedly been born as twin girls, nicknamed Lulu and Nana—and another woman is apparently pregnant with a similarly gene-edited fetus. Using CRISPR for this purpose is called germline editing, since the children born with the edited genes will be able to pass them along to their own kids.

The ethical concerns that people have raised about He's project include the specific gene targeted for editing, whether the parents gave informed consent, whether he failed to disclose conflicts of interest, and whether he violated of Chinese laws. The embryos were edited for couples in which the male partner is HIV positive. He apparently told the parents that the editing would substantially reduce the chances of their children becoming infected if they were ever exposed to virus. Critics point out that there many other treatments now exist that can prevent and ameliorate HIV/AIDS without resorting to the novel process of gene-editing embryos. The risks of off-target deleterious mutations resulting from CRISPR editing, they argue, outweigh the benefits of gene-editing to lower the risk of HIV infection.

Another issue raised by critics is that the twins whose CCR5 receptors have been disabled may be more susceptible to other diseases such as West Nile virus, some tick-borne infections, and influenza. Fair enough, but it should be borne in mind that some 10 percent of Europeans already naturally inherit genes for disabled versions of their CCR5 receptors. Genomes—natural or engineered—will always involve tradeoffs.

In its 2017 report on human genome editing, the U.S. National Academy of Medicine set out criteria declaring that germline editing should be carried out only in the "absence of reasonable alternatives" and if they address a "serious disease." STATnews observes that criteria such as "unmet" or "serious" medical need are highly subjective. He argued that HIV/AIDS carried such stigma in China that protecting babies from ever acquiring the virus satisfied those criteria. It is worth noting that Xinhua, the official Chinese news service, reports that "HIV carriers are not allowed to have assisted reproduction." He may well have violated this law by seeking to help families in which the would-be fathers are HIV positive. In contrast with China, many fertility clinics in the U.S. offer assisted reproduction services to help HIV positive customers bear healthy children.

Setting aside He's specific project, what about using CRISPR to correct genetic diseases that take only one copy (autosomal dominant) of a defective gene that causes illnesses such as Huntington's disease, hypertrophic cardiomyopathy, neurofibromatosis, or familial hypercholesterolemia? In such cases, how much risk should fully informed parents be allowed to take on behalf of their hoped-for children?

In He's case, it is not clear how well-informed the parents were with regard to the risks and benefits of CRISPR editing. Rice University genetic engineering professor Michael Deem was an academic advisor to He and held a small stake in a couple of He's startups. Deem told the AP in November that "he was present in China when potential participants gave their consent and that he 'absolutely' thinks they were able to understand the risks." Deem's lawyers issued a statement in December denying that he had been involved with He's research.

He claimed that his project received approval from the ethics review committee at the Harmonicare Women and Children's Hospital. The privately owned hospital denied any association with He. Curiously, Chinese media don't report that there was no ethics review committee, but that the committee was not properly registered with the city's health authorities. The hospital additionally claims that He forged the signatures of review committee members. If he did, that's clearly wrong. On the other hand, given the highly negative reaction to He's research, it wouldn't be too surprising if the hospital's managers are engaged in a bit of revisionist history.

He most likely did not disclose to the hoped-to-be parents that he has filed for patents related to his genome-editing research. Certainly He should have disclosed, but at least some studies find that patients are not overly worried about researchers' financial ties.

Chinese law regarding the implantation of gene-edited embryos is a bit murky. The New York Times reports that it is "not immediately clear which specific laws Dr. He was accused of breaking." (It also quotes the Peking University health law researcher Wang Yue, who notes that "Even though the Ministry of Health has issued ethical rules, the legal responsibility is unclear and the penalties are very light.") As BioEdge suggests, He's chief problem with Chinese authorities is that he violated "China's first law of science," that is, "do not embarass the government."

Setting He aside, let's consider the question of what, if anything, is ethically wrong with parents taking advantage of technologies like CRISPR to protect their children from diseases. Don't answer that it's wrong because it's not safe: That's not the question I'm asking. If the safety issues are resolved and the technique is perfected, would there still something unethical about editing the genomes of human embryos?

Some bioethicists ominously intone that such engineering involves "unwilling and unconsenting human lives." Yet no one ever gives consent to be born, much less to be born with a specific complement of genes. With respect to consent it does not really matter ethically whether that complement is natural or engineered.

According to the United Nations' Universal Declaration on the Human Genome and Human Rights, the human genome is the common "heritage of humanity"; on that basis a U.N. bioethics commission argued for a permanent "moratorium on genome editing of the human germline." But enabling governments to decide what sort of children can and cannot be born is the very definition of eugenics. After all, what horrors are parents likely to inflict on their progeny by means of gene-editing? Less risk of disease, stronger bodies, and nimbler brains. While some parents will certainly make mistaken choices as gene-editing and assisted reproduction technologies advance, they are surely far more trustworthy guardians of the human gene pool than any set of well-intentioned bureaucrats.

How worried should the rest of us be about how gene-edited children will affect future generations? Consider three scenarios. If the edited genes are beneficial to individuals then they will be beneficial to their offspring. If the edited genes tragically turn out to be harmful to individuals, then like deleterious natural genes they will tend to be selected against in reproduction and thus not spread to many folks in future generations. But an even more likely prospect is that edited genes that turn out to be harmful will be fixed by more advanced genetic engineering before they are passed along to the next generation.

Given that, the new international commission on human genome editing should firmly reject all calls to ban human genome editing and instead focus its efforts on devising standards for deploying this technology safely.