By Jeanne Snelling and Mike King

Chinese researcher, He Jiankui, claims to have implanted CRISPR-cas9 gene-edited embryos into potentially six women resulting in at least one successful pregnancy (of twins). Given the unconventional and inadequate way information has been released by He, and the fact that the research has not had thorough oversight, the facts are uncertain. If what He is claiming to have done is true, his rogue act constitutes a departure from a vast array of ethical, legal, and professional norms that have thus far—for good reason—prevented use of this technology in human reproduction.

According to the Associated Press, He’s “AIDS vaccine Development Programme” recruited research participants through an AIDS advocacy group, seeking men infected with HIV but with unaffected partners.  All of the males were being treated with standard HIV therapy, with their infections “deeply suppressed”. In these circumstances, the small risk of transmission to offspring could be managed with precautionary measures not involving gene manipulation. Hence, the goal of the gene editing was not to prevent transmission of HIV, but to confer an advantageous gene alteration that conferred immunity to HIV. The couples were offered free fertility treatment for participating in the research.

Aside from its potential impact on long-term health, HIV/AIDS is associated with social stigma.  The AP and others report that in China, HIV positive individuals may have difficulty gaining and retaining employment, or accessing medical care.  In this context, being born with the desirable trait would undoubtedly be advantageous, particularly if you were born into a high-risk population.  However, being blessed with the gene mutation by virtue of the genetic lottery, and having it engineered by CRISPR-cas9 given the current state of the science, are very different things.

There is an international consensus that conducting preclinical CRISPR to improve gene editing is ethical, but that it should not be used to establish a pregnancy. In 2015, the International Summit on Human Gene Editing co-hosted by the US National Academies of Sciences, the UK Royal Society, and the Chinese Academy of Sciences released a statement on CRISPR. It stated that clinical use of germline gene editing would be irresponsible until: “the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives”; there is “broad societal consensus about the appropriateness of the proposed application”; that “any clinical use should proceed only under appropriate regulatory oversight” and “the international community should strive to establish norms concerning acceptable uses of human germline editing and to harmonize regulations, in order to discourage unacceptable activities while advancing human health and welfare”.  The US National Academies of Sciences more recently claimed that “more research is needed before any germline intervention could meet the risk/benefit standard for authorizing clinical trials.”

The translation of CRISPR research from the laboratory into the clinic needs to overcome significant clinical hurdles including risks of: incomplete editing; off-target mutations; on-target mutations with unintended/unwanted benefits; and problems with mosaicism whereby a gene edit is not present in all human cells. Pre-clinical trials, such as studies on non-human primates, are generally necessary before conducting first-in-human trials.

Following the Nuremburg trials and the Declaration of 1947, the ethical conduct of biomedical research is recognised as a global concern.  The most recent version of the International Ethical Guidelines for Health-related Research Involving Humans reiterates that scientific value and respect for the rights of participants underpins the ethical conduct of research.  De minimis standards of ethical clinical research are: that it is based on rigorous research design including adequate pre-clinical trial data; careful subject selection in first-in-humans trials; the potential risks and benefits are known and the risk benefit ratio is considered reasonable in the circumstances; the participants give fully informed and voluntary consent; the research is subject to adequate independent ethical oversight and data safety mechanisms are initiated where necessary; and any conflicts of interest are transparently disclosed and managed.

The AIDs Vaccine Development Programme, from what is currently known in the public domain, is in apparent contravention of all of these minimal standards. (It even contravenes some of He’s own proposed ethical standards, published recently, and without disclosing conflict of interest.) The risks of CRISPR are well-known. There is no adequate pre-clinical data to justify a first-in-humans trial. The quality of the information provided to the women who participated in the research is uncertain, but it is possible that they may have been induced to participate in the study by the offer of free fertility treatment.  Of great concern is that the embryos on which the procedure was performed, and which have reportedly resulted in the birth of two girls, have been exposed to risks with no offsetting benefit to their health.  In addition, any adverse changes may be passed on to their future children, should they have them.  While it has been reported that Shenzen’s private HarMoniCare Women and Children’s Hospital ethics committee approved the study, the hospital has denied it approved the study.

In 1982, the US Presidents Commission for the Study of Ethical Problems in Medicine & Biomedical & Behavioural Research stated that the question that deserves careful thought by science and society is “by what standards, and toward what objectives, should the great new powers of genetic engineering be guided?”   While the social and ethical issues are being considered by national bodies such as the United Kingdom’s Nuffield Council and the Royal Society of New Zealand, He has presented the world a fait accompli. The last thing the world needs is scientists gone rogue.

Authors: Jeanne Snelling and Mike King

Affiliation: Bioethics Centre, University of Otago, Dunedin, New Zealand

Competing interests: None disclosed