Perhaps a Chinese scientist shortened the life of genetically modified girls

The missing piece of DNA, 32 pairs longbases, excised in the middle of the CCR5 gene, may be the most studied mutation in human history. Spontaneous removal, which arose thousands of years ago, is strikingly connected with one of the most terrible human diseases: HIV / AIDS. People who inherit this mutation from both their parents naturally have immunity. Two people who managed to be cured for all the time were subjected to bone marrow transplantation from people with the Δ32 mutation.

The pharmaceutical industry has investedsignificant funds in trying to recreate the benefits of this natural anomaly using drugs and genetic engineering. And last year, a Chinese scientist named He Jiankui used CRISPR, trying to endow two human embryos with the Δ32 mutation and immunity to HIV. His experiments were widely condemned for violating ethical boundaries and violating Chinese law. They also ended with the birth of twin girls. But this is not the end.

What will happen to the Chinese girls who have edited the genes?

Last week, it turned out that clinics intreatment of infertility from around the world turn to Heh for advice, offering to use the editing of the CCR5 gene using CRISPR as a service for future parents. However, a new study suggests that such a procedure may actually be a death sentence and lead to early death.

This is because the Δ32 mutation does not onlypeople resistant to HIV, but it also reduces years of life. In a study published yesterday in the journal Nature Medicine, scientists at the University of California at Berkeley analyzed more than 400,000 genomes and medical records stored in the British Biobank (Biobank), a huge British database that was recently opened to scientists. And it turned out that people with two copies of the Δ32 mutation die 21% more often than people with or without a single copy.

"It is believed that one mutation leads toone thing, but biology doesn't work that way, ”says Rasmus Nielsen, an evolutionary biologist and co-author of the article. The results of scientists illustrate how a single mutation can influence many different traits simultaneously, and in ways that are very difficult to predict. “I hope that now it will become clear that before modifying the human genome with CRISPR, we need to carefully consider all the possible consequences of the mutations that we create.”

Nielsen was interested in using dataBritish biobank to study how the frequency of genes is formed under the pressure of modern life. They had several genes to consider, but after the Xe scandal in November 2018, they decided to focus on CCR5.

They found two lines in the data of the British biobankevidence to suggest that in our day CCR5 actually bears exceptional harm. In the first analysis, scientists traced how long people continued to live after registering in a biobank survey. It turned out that at the age of 41 to 78 years old people with two copies of the Δ32 mutation had a significantly higher mortality rate. They also noted that the study included far fewer people with two copies than expected, which, in their opinion, means that such people are less likely to live to middle age than the general population.

“Something led to the removal of people with two copies of the mutation [from the database], and the likely explanation is increased mortality,” says Nielsen.

The British Biobank data did not reveal thatspecifically could kill these people, but earlier studies in mice showed that the lack of a functional CCR5 gene increases susceptibility to other deadly infections, including influenza and West Nile virus.

To understand how the winds could changeevolution, it will be useful to learn something about the history of the origin of this mutation. Several thousand years ago, somewhere in the Nordic countries, devastated by plague and smallpox, a child was born who lacked a large piece of DNA in the CCR5 gene. This gene encodes a receptor on the surface of immune cells that coordinates responses to the invasion of pathogenic microorganisms. And this spontaneous removal torpedoed CCR5 production: one copy reduced the number of receptors in the cells, two copies erased the receptor completely.

At another time and in another place such a mutationCould be a problem, but at that time it turned out to be an evolutionary surprise. The family of the man and his descendants miraculously outlived their peers. Today, the Δ32 mutation occurs in about 10% of the European population with a decreasing gradient from north to south. Natural selection pushed it through the population 100 times faster than if it were a neutral genome change. But with the invention of vaccines and the eradication of diseases such as smallpox, over the past century, mutation has become less useful. Today, this mutation is frankly harmful, as the study shows.

In any case, in populations similar to thosethat were at Biobank. These data cannot be reasonably extrapolated to China, for example, where the pathogenic environment and the genetic background of people are very different from the British. But this suggests that the genetically modified twins will need to be closely watched throughout their lives. According to reports, the girls will remain under the control of the government in Guangdong, where they were experimenting with them.

For bioethics like Hank Greeley of Stanford, these latest discoveries further increase the risks of CRISPR operations, far outweighing the potential benefits.

“I thought that the He experiment had exceeded the ethical limit once in 50 times,” he says. "And now he has become even more risky."

The big problem is that none ofgenetically modified girls were not infected with HIV — they could have avoided the disease using safer, more proven methods such as condoms and prophylactic drugs.

But for people who have already become infected, scientists say, it is still more profitable to tolerate a mutation.

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