杏吧原创

Russian biologist Denis Rebrikov has told New 杏吧原创 that he still plans to use CRISPR genome editing to prevent children inheriting deafness, despite a major international report out today saying it isn鈥檛 yet safe enough to try in people.

鈥淲e are still planning to correct the inherited hearing loss mutation in [the gene] GJB2, so that a hearing baby is born to a deaf couple,鈥� says Rebrikov, who is at Pirogov Medical University in Moscow.

Three children whose genomes were altered by CRISPR gene editing were born in China in 2018 and 2019. The unauthorised creation of those embryos caused concern around the world and spurred scientific institutes to set up the International Commission on the Clinical Use of Human Germline Genome Editing, a group of 18 doctors, biologists and ethicists from 10 countries tasked with drawing up guidelines for how to proceed in a responsible way.

The main conclusion of its report, out today, is that genome editing isn鈥檛 yet safe and effective enough for altering human embryos before implantation in the uterus. 鈥淭he criteria for safe and effective heritable human gene editing have not yet been met,鈥� says Haoyi Wang at the Chinese Academy of Sciences, who is on the commission.

The reason is that existing methods can cause unintended genetic mutations and also may not correct the condition-causing mutation in every cell, an issue known as mosaicism. However, the technology is advancing so fast that it might be ready for use in just a few years, says Wang.

These problems aren鈥檛 a deal-breaker for using CRISPR as a treatment for serious conditions such as cancer or sickle cell, as the potential benefits outweigh the risks, and the changes CRISPR makes in these cases are not heritable. Many trials are already under way.

However, there is widespread agreement that it isn鈥檛 yet safe enough to use CRISPR to make heritable changes by editing human embryos 鈥� with Rebrikov being one of the few exceptions.

He told New 杏吧原创 last year that he plans to use to CRISPR to correct a recessive mutation in the GJB2 gene that causes deafness.

Almost all genetic conditions can already be prevented by screening IVF embryos before implanting them, known as preimplantation genetic diagnosis, or PGD. When both parents are deaf because of a GJB2 mutation, however, all their children will be deaf too; PGD isn鈥檛 an option.

When asked to comment on the commission鈥檚 report, Rebrikov confirmed that he still plans to go ahead.

He didn鈥檛 mention the safety issue. Nor is it clear if Rebrikov has any official approval for his plans. In October 2019, the Russian health ministry said . But, as in many other countries, there are no laws explicitly banning it.

Even if CRISPR genome editing gets to the point where it is safe and effective enough for altering human embryos, its use to prevent deafness would be controversial. 鈥淚 would not be supportive of it being used first for deafness,鈥� says Sarah Norcross at the Progress Educational Trust, a UK charity to advance public understanding of science.

The commission鈥檚 report recommends that if any countries decide CRISPR is safe enough to use for making heritable changes, it should be limited to a few situations.聽First, those in which prospective parents have no option for having a genetically related child that doesn鈥檛 inherit a disease.聽Second, those where PGD is unlikely to succeed 鈥� that is, in situations where less than 1 in 4 viable IVF embryos would be free of the condition. Even so, the report recommends that couples should have attempted at least one cycle of PGD without success.

Rebrikov鈥檚 plans do meet these criteria, but the report also recommends that heritable genome editing should initially be limited to serious conditions caused by a mutation in a single gene.

鈥淢y model is hereditary hearing loss, so, this can 鈥榖e limited to serious single-gene diseases鈥�, I guess,鈥� says Rebrikov. However, the report defines a serious single-gene condition 鈥渁s one that causes severe morbidity or premature death鈥�. Many would argue that this definition excludes deafness.

While Norcross doesn鈥檛 support Rebrikov鈥檚 stance, she and others are critical of the report鈥檚 recommendations for initial uses. 鈥淚t does seem rather narrow,鈥� she says.

For instance, Norcross doesn鈥檛 agree with the recommendation that couples should have already tried PGD at least once. 鈥淧GD is not easy, and it鈥檚 not necessarily available,鈥� she says. 鈥淭he woman鈥檚 age does not stop while all this is going on.鈥�

Nor does Norcross think the initial uses need to be limited to single-gene conditions. 鈥淚t鈥檚 not necessarily irresponsible to make two edits,鈥� she says.

Many conditions are caused by multiple mutations, and PGD is of little use for preventing these.