Chinese Researcher Reports First Gene-Edited Babies

Dr. He Jiankui, a professor of genetics from Southern University of Science and Technology in Shenzhen, China, has created significant controversy by claiming to have edited the genes of two recently born twin girls, named Lulu and Nana (it’s not clear if these are their real names or just designations, but it seems like the latter). There are several layers of controversy here, starting with the fact that his claims have not yet been verified.

He has not yet published his claims, but says he submitted them to a peer-reviewed journal. If correct, what he did was use CRISPR technology to alter the CCR5 allele of the twin girls. CCR5 is a gene that is involved with T-cells and is an important receptor:

CCR5 is the main coreceptor used by macrophage (M)-tropic strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2, which are responsible for viral transmission.

There are versions (alleles) of the gene, and in people who have two copies of this allele they are highly resistant (but not immune) to HIV infection. These resistant alleles are more common in those of European descent. For those with one copy of the allele they progress more slowly to AIDS after HIV infection. This is an important discovery, and is currently the subject of research, mainly to find drugs that exploit this aspect of the viruses’ life-cycle.

He says in a video that he “removed” the girls’ CCR5 gene when they were at the single cell stage, after IVF. Their father (called “Mark” in the video) has HIV. No mention is made whether or not the mother does, but that is obviously the concern.

He defends his actions by citing the way those with HIV are treated in China, including refusal of medical care and even forced sterilization. If these claims are true, that does alter the context of his decision to some degree, but still does not fully justify it.

There are scientific and ethical questions with this case. The first scientific question is – can this technique work? There is solid evidence behind the role of the CCR5 gene, and altering or removing it is a plausible way to increase resistance to HIV infection.

How about the CRISPR technology the He used to remove the gene? We have discussed CRISPR before on SBM, it is a new and exciting technology that makes gene editing much faster and cheaper. It is a boon for research. The technology, derived from bacteria, allows for the targeting of specific gene sequences in DNA, and then slices then out and can even replace them with an alternate sequence.

However, this is a very new technology, presented first in 2012. There are still many questions, such as the risks of off-target genetic changes. The CRISPR enzymes do target the desired sequence, but may also slice out similar sequences that are not the desired target. Exactly how many off-target changes occur, and how to adjust CRISPR to affect such changes, is still an active area of research.

This is the primary concern about what He did – there are still unknown risks for using CRISPR to alter a human genome. He claims that they did full genome sequencing before and after the CRISPR treatment and that the only change to the genome was the removal of CCR5. If true, this is reassuring, but again these claims have not been peer-reviewed. A big question is – where did they look for the changes? Did they really crawl the entire genome to look for changes, even in apparent “junk” DNA? Or did they just look for changes in similar genes?

In the end, however, both CRISPR technology and using CCR5 as a target to treat or prevent HIV are good solid science, and it is entirely plausible that the gene editing He did on the two girls worked and will have the intended effect without side effects. It’s possible – but we don’t have enough data to know what the risks are, and that’s the problem.

Any medical intervention on a human, even when they are just a single cell, needs to be evaluated for risks vs benefit. The primary criticism of what He did is that the benefit for the girls is dubious, because transmission of HIV from mother to child can be prevented by treating the HIV to minimize the viral load. With aggressive treatment the risk of transmission can be reduced to 2% or less.

There is also the issue of transmission from the father’s sperm, but existing treatments here are even more effective. In addition to minimizing the father’s viral load prior to sperm donation, you can wash the sperm to remove the virus. There are no known cases of HIV transmission through sperm during IVF if these precautions are taken.

How much will his gene-editing treatment reduce their chances? We don’t know. But even if we assume it reduced their infection rate to zero percent, we still need to know the other side of the equation – the risk.

This is where the strongest criticism is, that He was essentially doing unapproved human research. I am not as familiar with the regulations in China, but there are international standards for doing human research, to protect the subjects. The reaction to He’s announcement makes it seem like a surprise, which further implies that he did not get all the required approvals prior to doing his research.

He also says that there is another mother pregnant with a child that he gene-edited during IVF, but without further details.

In the end I hope that everything works out well for Lulu and Nana, and if He’s reporting so far is accurate it seems like it is. This also may become a viable, and even standard, treatment for those who need it. But He’s intervention was premature.

The deeper ethical questions remain. What are the ethics of deliberately editing the genes of humans? We do have to make a distinction between somatic cell gene editing, and reproductive cells change. If you only change the mature non-reproductive cells in a person, whatever changes you make stop with them. However, if you change the reproductive cells, those changes can be passed on, and therefore can get into the human population. Because He made changes at the single-cell level, those changes will affect all of the girls’ cells, including their reproductive cells. That is a much bigger deal, ethically.

I do think that targeted gene editing to treat disease will become generally accepted, and probably more quickly than most people realize. CRISPR is a powerful technology, and it is advancing quickly. Once we have a better handle on its safety, it will be hard to deny parents the option of fixing a horrible genetic disease in their children.

The real controversy is in so-called “designer” babies – enhancing or choosing traits that have nothing to do with health or disease.

The kind of intervention that He did is itself reasonable, and will probably be adopted before too long. The real problem is that he jumped the gun. CRISPR technology is still too new. We need to take the time to perfect the technology a bit more, and get better data on its safety. Then, with full oversight and transparency, we can talk about research protocols to study its use in humans.

If you watch the video it’s clear that He meant well and sincerely wanted to help the parents. He also does come off as having a bit of a savior syndrome. Ultimately that’s hubris, the same kind of hubris that drives a lot of snake oil. It’s not up to him to make himself into a savior and martyr. There is a process for determining what is ethical and appropriate, and there is no legitimate reason to bypass that process.