Genome edited babies: An unexpected reality

Tanya Brigden

19 December 2018

Last month, the world was shaken by stories circulating that genome edited twin girls  - Lulu and Nana - had been born in China. This news was leaked two days before the Second International Summit on Human Genome Editing, where Dr Jiankui He, the scientist responsible, presented his use of CRISPR technology in human embryos. His work targeted the CCR5 gene with the aim of inducing an otherwise rare variant that confers resistance to infection by HIV, and he has since revealed that a second pregnancy with edited embryos is underway.

Whilst these claims remain unverified, they are hugely controversial. He’s actions constitute a departure from the ethical, legal and professional norms that have - until now - prevented the use of genome editing in human reproduction. The implanting of an edited embryo is illegal in most countries, and whilst a report published by the Nuffield Council on Bioethics in July concluded that the use of germline genome editing could be morally permissible in some circumstances, these circumstances do not exist at present. Given this legal and ethical climate, there are a number of concerns and considerations surrounding He’s work and the birth of Lulu and Nana.

Disregard for global consensus

Internationally, there is a general agreement that genome editing of human embryos is not ready for the clinic. Although legal in China, He’s work violates Chinese ethical guidelines on embryonic genetic research. Internationally, stakeholder groups have been unanimous in calling for more research into safety and efficacy issues (such as off-target effects), broad social consensus on acceptable applications, and appropriate regulatory oversight before applying this technique clinically. Cross cutting this has been a desire for transparency to engender public trust and understanding.

Dr. He’s work, seemingly rushed and conducted covertly, contravenes the broad global consensus which has for some time now been ‘proceed with caution’, and shows disregard for the agreed boundaries adhered to by other members of the science and ethical communities.

No unmet medical need

Clinical trials are justified on the basis that they balance the potential benefits for research participants and for society against a myriad of potential harms. The most harmful interventions can only be justified on the basis, for example, that they address unmet medical needs in those with serious disease. In the instance of the twin girls, there is no unmet medical need that genome editing addresses.

The twin’s father is HIV positive, carrying a very small risk of HIV transmission to his offspring, and one that could be even further reduced by sperm washing and antiviral drugs. In the unlikely event that the twins had been born HIV positive, there are safe and effective ways to control and manage HIV, and those with the disease can live a normal life. Furthermore, CCR5 linked resistance seems not to be absolute - isolated cases of HIV positive patients that possess the rare CCR5 variant have been reported as some strains of the virus can enter cells via a different protein (CXCR4).

Would the public reaction have been different had the disease selected been serious and untreatable such as Huntington’s disease; a highly heritable and incurable neurodegenerative condition?

This experiment has exposed healthy babies to significant risk, with no offsetting benefit to their health. In addition, it has been acknowledged by the scientific community that there are problems with He’s approach which are not yet fully understood – these have been discussed extensively elsewhere.

Would the public reaction have been different had the disease selected been serious and untreatable such as Huntington’s disease; a highly heritable and incurable neurodegenerative condition? Whilst it would have been a more justifiable application of the technology, concerns surrounding He’s actions are far-reaching, and extend beyond the welfare of the individuals that he edited.

Crossing the line between therapy and enhancement

Did He’s experiment constitute a purely therapeutic application of the technology or has it crossed the blurred line towards enhancement? He’s aim appears to have been to make already healthy babies ‘healthier’. The goal of the genome editing was not to prevent transmission of HIV, but ‘to bestow a trait that few people naturally have: an ability to resist possible future infection with HIV’. What constitutes enhancement is disputed but can include accentuating ‘natural’ human ability. Given the social stigma surrounding HIV in China, having a protective gene mutation would be seen as advantageous.

Failure to adhere to ethical standards for clinical research

International standards for ethical clinical research on humans require adequate pre-clinical trial data, reasonable risk benefit ratio, fully informed and voluntary consent and independent ethical oversight, amongst other things. The AIDs Vaccine Development Programme, as He misleadingly entitled his study, was in contravention of these ethical standards.

Technologies are neutral, in that they can be used as a positive or negative force. How they are used, especially when their use has global consequences, is for society to decide, not an ambitious individual scientist exploiting a weak regulatory environment.

Not only was there no adequate pre-clinical data to justify a first-in-human trial, but the quality of the information provided to the couples who participated in the trial is uncertain, as is their understanding of the risks. The consent document used heavily technical language, and He himself took the parents through the informed consent; a process that he did not have the training to carry out. Of particular concern is the fact that the couples were offered free fertility treatment for participating in the research, which could constitute inducement. While He claims that Shenzen’s private HarMoniCare Women and Children’s Hospital ethics committee approved the study, the hospital has denied this.

Technologies are neutral, in that they can be used as a positive or negative force. How they are used, especially when their use has global consequences, is for society to decide, not an ambitious individual scientist exploiting a weak regulatory environment. The birth of these babies has prompted calls for an international agreement on embryo research, to prevent this happening again. Here in the UK, if targeted clinical use of embryonic genomic editing is to proceed, we need to review our own regulatory framework in order to entrench high ethical standards but also to build wider public trust.

 

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