(This article has been translated into French.)

In November 2018, a Chinese researcher made headlines with the news that he had created genetically modified babies using genome editing. The scientist, He Jiankui, claimed to have modified the CCR5 gene to make baby twins resistant to HIV. The pair became known as “CRISPR babies,” after the gene editing technology used.

A few days later, at the International Human Genome Editing Summit in Hong Kong, Jiankui announced that a second pregnancy was underway. The international scientific community greeted the news with dismay and indignation. By March, a group of leading scientists and ethicists had recommended a global moratorium on germline gene editing in the journal Nature.

In Canada, genetic modification of reproductive cells and early embryos – germline gene editing – is prohibited for research or clinical purposes. (It’s in the Assisted Human Reproduction Act, section 5(1)f.)

Nonetheless, here in Quebec, for the last 18 months the Commission de l’éthique en science et en technologie has been working to address the ethical issues raised by the genetic modification of reproductive cells and early embryos (germline gene editing).

This is part of the commission’s mandate, which is to raise awareness of ethical issues. And on this topic, its work is intended to support any eventual decisions about the future of the practice in Quebec and in Canada.

It released its recommendations in late March in a position statement, advising extreme caution and prudence. How can the recommendations help us to understand and evaluate the case of the Chinese researcher? By considering the following:

Health risks

Targeted gene editing involves intentionally modifying DNA to change specific structural or functional characteristics in an organism. It can be used to deactivate, modify, remove or replace genes. Gene-editing tools like CRISPR-Cas9 use nucleases (enzymes) to cut DNA, and engineered molecular guides to lead the nucleases to the targeted site.

Applied to reproductive cells and early embryos, gene editing can allow people who are carriers of disease-causing mutations to give birth to unaffected children. The technology is not yet fully developed and is associated with risks to the future child’s health:

  • First of all, the successful modification of a targeted gene can generate unexpected effects in a person because the same gene can play a role in several different individual (phenotypic) traits. For example, correcting the gene causing sickle cell anemia can increase the risk of contracting malaria.
  • Secondly, the intervention can trigger off-target unintentional genetic modifications with the potential to cause serious health problems such as cancer.
  • Thirdly, the embryo can exhibit mosaicism, i.e. the embryo’s cells might not all be genetically identical; some cells might be modified and others might not. In these cases, the child could still develop the disease that the intervention was supposed to prevent.

Moreover, unlike the genetic modification of the body’s cells (somatic cells), genetic modifications of germ cells and early embryos are transmissible to descendants. The risks associated with these modifications therefore affect not only the targeted cells, but also future generations and the genetic heritage of the human species as a whole.

We have no information about possible off-target mutations in He Jiankui’s work. However, the researcher revealed that half of the CCR5 genes in one of the twins was not modified, and placenta analysis showed signs of mosaicism. This can reduce considerably, if not totally, the protective effect against HIV that was sought.

In addition, the version of CCR5 whose protective effect against HIV is known is CCR5Δ32. He Jiankui attempted to mutate the normal CCR5 so that it became CCR5Δ32, but failed and thus created new CCR5 mutations, the effects of which are unknown.

To avoid these types of problems, the commission recommends the prohibition of any clinical application be maintained in Canada, meaning any application leading to pregnancy. It recommends that no clinical application be considered until a set of technical elements is validated in the context of preclinical research (for example: testing on animals) and following strict scientific standards.

For each nuclease-guide-target combination, we must assess the success of targeted editing, the absence of off-target mutations, the absence of mosaicism, absence of unintentional genetic modifications and so on.

What is the ethical justification for the intervention?

The benefits of an intervention must outweigh the risks associated with that intervention, in keeping with the ethical principles of beneficence and non-maleficence. Since germline gene editing is a new and radical intervention associated with potentially serious risks, these risks must be justified by substantial benefits for the future child.

Therefore, if Health Canada decides one day to allow clinical applications (i.e. those leading to pregnancy), the commission recommends this type of intervention be used solely to prevent very serious genetic diseases that have a high probability of manifesting, and for which there is no available therapeutic or reproductive option.

Several critics have denounced He Jiankui for the futility of his intervention. HIV is not a disease that can be transmitted genetically. It is an infectious disease. Although the father was a carrier of the retrovirus, cases of father-to-child transmission are very rare. But there are effective options for preventing and controlling HIV.

He Jiankui, a Chinese biophysics researcher, at the Summit on Human Genome Editing on November 28, 2018 in Hong Kong. Photo by Voice of America.

Another useful distinction in this case is between genetic modifications that aim to restore health and those that seek to enhance human capacity. In germline editing, enhancement is the application of the technology to improve the child’s biological capacities beyond the level needed for good health and even beyond the current limits of the human body. This type of objective raises many controversial philosophical and ethical issues for which there is no social consensus.

Therefore, if Health Canada ever decides to permit clinical applications, the commission recommends the use only of modifications that would transform a disease-causing mutation into a normal human gene (for example, the most common version of the gene within the population).

By contrast, He Jiankui tried to modify a completely normal, widespread and healthy gene (CCR5) and replace it with a very rare version (CCR5Δ32), which can be conceived as a form of enhancement. If germline gene editing becomes desirable one day, it should be fully dedicated to equalizing the conditions and opportunities of those who have been unlucky in the genetic lottery.

The need for public deliberation

Science and technology policies should be based on a certain level of social consensus and public participation. This ensures that the process is more democratic and is perceived as being more legitimate by the general public. Hence, it is important to involve the public and engage in democratic dialogue on the issues raised by the modification of germ cells and early embryos. If a true dialogue is to take place, participatory approaches should be used, and methods designed simply to convey information or “sell” the technology should be set aside.

Information must be provided, of course, but it is important to go farther by giving citizens the opportunity to express their concerns, and by including as many different views as possible.

Therefore, the commission recommends that government support organizations with expertise in public education and consultation so that they can organize interactive activities for the general public on the genetic modification of germ cells and embryos (for example: scientific exhibitions, public consultations and debates, and so on).

For more detailed information, see the commission’s complete position statement in French or the summary in French and in English. The statement is titled: Genetically modified babies: Ethical issues raised by the genetic modification of germ cells and embryos.

This article is part of the Addressing the Gaps in Canada’s Assisted Reproduction Policy special feature.

Photo: Shutterstock/By Blackboard

Do you have something to say about the article you just read? Be part of the Policy Options discussion, and send in your own submission. Here is a link on how to do it. | Souhaitez-vous réagir à cet article ? Joignez-vous aux débats d’Options politiques et soumettez-nous votre texte en suivant ces directives.

Jocelyn Maclure
Jocelyn Maclure is professor of philosophy at McGill University and holds the Jarislowsky Chair in Human Nature and Technology. He is president of the Commission de l’éthique en science et en technologie du Québec.
David Hughes
David Hughes is an ethics advisor at the Quebec Ethics in Science and Technology Commission (CEST).

You are welcome to republish this Policy Options article online or in print periodicals, under a Creative Commons/No Derivatives licence.

Creative Commons License