Widespread condemnation is the chief response to Chinese bioengineer He Jiankui's claim that he used CRISPR gene-editing to alter the genes of embryos who have now been born as twin girls. The editing aimed to increase their resistance to HIV infection. The Chinese government claims that it has now shut down He's work.
New York University bioethicist Arthur Caplan denounces He's efforts as a "moral monstrosity of an experiment." Just how morally monstruous is what He claims to have done?
Caplan argues that He "is a moral idiot who has engaged in a renegade experiment that may well setback the very promising field of germline genetic engineering a decade or more." Why would this set back the field? "Fear of changing genes that are passed from one generation to the next?—?germline engineering?—?runs deep," explains Caplan. "Altering the inherited properties of our children strikes many as manufacturing people. Add a bit of 20th century eugenics à la Nazi Germany into the mix and fear turns rapidly into prohibition."
If the fear of germline gene-editing really does run deep, one big reason is that many of Caplan's fellow bioethicists have long been scaremongering about it. However, a recent Pew poll finds that such fear does not run all that deeply among Americans—72 percent of respondents said that changing a baby's genetic characteristics to treat a serious disease that a baby would have at birth is OK; and 60 percent agreed that gene-editing was appropriate to reduce the risk of a serious disease that would occur over the lifetime of a prospective baby.
Caplan may have a point though about He's work provoking folks to demand prohibition. Sadly, in response to He's claims, CRISPR pioneer Feng Zhang has done just that and is now calling for a global "moratorium on implantation of edited embryos."
Much to his credit, Caplan does note: "I am not among those who think it's unethical to change the genes of our children. If it is possible to eliminate forever diseases such as cystic fibrosis, muscular dystrophy, hemophilia, sickle cell disease, fragile X syndrome, Huntington's disease, and a slew of other genetic killers that plague humanity, then I think germline genetic engineering is ethically sound and must be pursued."
So if germline editing in itself is not immoral, what is ethically wrong with what He claims to have done? Caplan gives five reasons: safety, lack of disclosure with regard to a published paper on the ethics of therapeutic reproductive technologies, non-publication of results, conflict of interest, and the provisions that may or may not have been made in case the kids turn out to have been harmed.
With respect to safety, He claims that he validated his engineering techniques via three years of work involving mice, monkeys, and then human embryos. One worry among researchers is that CRISPR may have caused off-target mutations in the twins' genomes. Such mutations might hit other genes causing them to malfunction in deleterious ways.
How big a concern is this? Harvard geneticist George Church offers some perspective on CRISPR off-target risks in an interview at Science. Asked about the risk of off-target effects, Church observed, "Let's be quantitative before we start being accusatory. It might be detectable but not clinical. There's no evidence of off-target causing problems in animals or cells. We have pigs that have dozens of CRISPR mutations and a mouse strain that has 40 CRISPR sites going off constantly and there are off-target effects in these animals, but we have no evidence of negative consequences."
Caplan argues that He's ethics paper must be withdrawn because its conclusions are suspect owing to the fact that He's co-authors must have known about his embryo gene-editing before they collaborated on it. By the way, it was published online two days after the revelations of He's work. One notably correct observation in the ethics paper is that, in describing prior biotech reproductive advances, journalists have constantly deployed
"the overused term 'designer baby': this is an epithet aimed at invoking disgust, which is a common mechanism behind hate. Parents hope to protect their newborn's life from a known debilitating, familial disease. Call them 'gene surgery babies' if one must or better yet ordinary people who have had surgery to save their life or prevent a disease."
For what it's worth, the ethical principles outlined in the paper do not seem all that controversial. They include using gene-editing only for serious dieases, respecting the gene-edited child's autonomy, and rejecting genetic determinism.
Caplan has He dead-to-rights when he objects to the fact that He has not published his results so that other researchers can evaluate his claims. Science by YouTube video is not science. He claims that the results of his research were "leaked unexpectedly" and that he has now submitted a paper detailing his work to a scientific journal. Given the uproar, however, it will take a very brave editor to publish it. For the sake of the field and the twins, let's hope that such a brave editor exists.
Caplan also points out He has filed patent applications on his work. This presents a number of possible conflicts of interest, not least of which is that patients are being recruited who may not know the He stands to benefit financially from his research. Interestingly, the author disclosure statement in the ethics paper claims "no competing financial interests exist." Really?
Finally, Caplan suggests a lack of provisions for addressing health problems that might later arise from the twins' gene-editing is ethically suspect. Is that right? Consider that children born by means of other assisted reproductive techniques are at a slightly higher risk of birth defects than naturally conceived kids. Physicans are not generally held responsible for those outcomes. Assuming similar levels of informed consent, why should the standards be any different for the twins? In any case, He says that he plans to "monitor the twins' health for the next 18 years, with the hope they will consent as adults for continued monitoring and support."
As noted, Caplan fully appreciates the power of germline editing to alleviate human suffering, but flinging around terms like "moral monstrosity" is not helpful in furthering the discussions that will lead to achieving that goal. Such talk will set back, rather than advance, this important research.
Harvard Medical School Dean George Daley offered a more measured response: "The fact that the first instance [of gene-editing] came forward as a misstep should in no way leave us to stick our heads in the sand and not consider the very, very positive efforts that could come forward," Daley said. "I hope we just don't stick our heads in the sand."
We should all hope so.