life (with) science

A Chinese scientist has revealed that the first two gene-edited babies are born in China as part of a questionable research project. This poses a threat to the scientific community’s credibility. Can science still regulate itself? And what are the consequences of this controversial event?

Wow it’s been quite a long time since my last post. Nonetheless, something quite controversial has happened a few weeks ago and I couldn’t possibly let this one go without clearing my thoughts around it. I hope it won’t take me another comparable event to keep going. Let’s get to it.

At the end of November, a Chinese scientist, He Jiankui, revealed that the first two gene-edited babies, two twin girls, were born in China as part of an undisclosed research project aimed at creating children resistant to HIV infection. The study has not been peer-reviewed nor published in any scientific journal, and the news has been released in the form of an exclusive interview to the Associated Press, and a series of videos on YouTube.

In the interview with the Associated Press, He, researcher at the Southern University of Science and Technology of China in Shenzhen, explains that he enrolled seven couples, and eventually impregnated one woman with embryos that had been edited using CRISPR-Cas9 to disable the genetic pathway HIV uses to infect cells. He claims 16 out of a total of 22 embryos were edited, and six implant attempts were performed before achieving a successful pregnancy.

Following the release of the article and videos on November 25 and 26, He presented his work at the Second International Summit on Human Genome Editing in Hong Kong. During the question session, He ended up revealing that another pregnancy is ongoing.

Is it worth the risk?

The choice of HIV counteraction as the target for this controversial research seems to be a rather poor one. Taken all together, the project’s motivations and mean of action do not justify the risk and the consequences of modifying the DNA of viable embryos for good. We must remember that these two girls have their genome irreversibly modified, and, most importantly, that they will pass these modifications over to their children.

“His choice of gene was a terrible one” Helen O’Neill, Molecular biologist at the University College London, told the New Scientist. “If it was a life-threatening disorder that has no other treatment, people would have found it more justifiable. The impression among the scientific community is that this was the low-hanging fruit, because there had been a lot of research into [this gene]”.

He selected a couple where only the man is HIV positive. Since the mother is not infected, the couple’s children were not exposed to a higher risk of being infected by the virus to begin with. They had the same chance to become HIV positive as has any other person. So, is it worth the risk of irreversibly editing the children’s DNA?

To make the two twin girl resistant to HIV, He deactivated the gene CCR5, which carries the information for the CCR5 protein, a receptor found on white blood cells’ membrane. White blood cells lacking the CCR5 receptor become “invisible” to HIV, granting a sort of immunity to its attack. This is the same target used in another Chinese studies on human embryos published in 2016 that I described here. However, deactivating CCR5 does not grant total resistance against HIV. Some HIV strains don’t use CCR5 but other proteins to infect cells.

Another disturbing aspect is that, as stated by He Jiankui himself to the Associated Press, only one of the two girls has a complete deactivation of CCR5 on both the DNA copies, while the other girl has the deletion in only one copy. This means that the CCR5 receptor is still produced and that she didn’t gain any benefit from the gene editing. Is it worth the risk?

Then, there’s the elephant in the room: off-target mutations and mosaicism. Although the CRISPR-Cas9 gene editing technique is getting more and more efficient, the risk of off-target mutations is still concrete. Having off-target mutations means that further to editing the targeted gene, CCR5 in this case, CRISPR-Cas9 might randomly bind and edit other DNA strains, with unforeseeable consequences on the embryo.

Mosaicism arises when a gene editing is successfully performed only on some of the cells composing the embryo. The resulting embryo is a collage of modified and unmodified cells. Gaetan Burgio, geneticist at Australia National University in Canberra, said that there are evidences in He’s data that could suggest the presence of mosaicism. Once again, is it worth the risk?

The only way of knowing if the two girls’ DNA contains off-target mutations or mosaicism would be to perform a complete gene sequencing. However, no one apart from He and the parents has access to the girls, and, therefore, no scientist has yet been able to perform a DNA sequencing.

A fail for the scientific community?

Reasonably enough, this study has taken the scientific community by storm and triggered an almost unanimous outcry. Every aspect of this issue, from the use of a gene-editing technique on viable embryos, to the achievement of the first “designer babies”, as well as the complete disregard for ethical and scientific review, forces to question the ability of science to regulate and control itself.

He’s undisclosed research can backlash on the entire scientific research. There is the concrete possibility that some countries might react by passing new, more restrictive legislations as a political response to this scandal. “The thought I kept having was the potential for rogue scientists to use this in unethical ways. It’s a real risk,” said Jennifer Doudna. Indeed, as pointed out by David Baltimore, this research shows that the scientific community cannot possibly be able to regulate itself to the point of preventing any rogue scientist from using technologies such as gene editing in dangerous ways.

However, the scientific community is not meant to be some sort of police. The scientific endeavour takes place within the boundaries of evidence-based trust between peers. Scientists must necessarily trust that other scientists’ research follows solid scientific and ethical principles. As J. B. Hurlbut and J. S. Robert wrote on The Conversation: “The crucial question is not what rules were broken, but what – and whose – judgments about what is right and appropriate should rule the human future. Deeming He “crazy” and a “rogue” does not answer the question of what went wrong”.

But there’s another aspect of this study that I find particularly alarming: the mean of communication. The way He unveiled and “publicised” his study could be extremely harmful to science’s credibility in the long run, even more harmful than the study itself. I will talk about these aspects of communication in a following post soon.

So, stay tuned because there’s more coming. Thank you for sticking with me and reading this article. I wish you a pleasant end of 2018!

If you liked this post you might like these other ones I wrote:
The dawn of the planet of gene editing therapies
Welcome to Gattaca, part 1, 2, and 3.

Header image: Ernesto del Aguila III, National Human Genome Research Institute, NIH via Flickr