The genetic mutation protecting against HIV linked to a decline in life expectancy

The genetic modification that a Chinese researcher has done on binoculars born in 2018 is linked to a shorter life expectancy, according to a study. This discovery shows the risks of transferring technologies to humans that are not fully understood.

In November 2018, there was an uproar in the global scientific community after a Chinese researcher named He Jiankui announced the birth of the first genetically modified humans.

These twins, known only under the pseudonyms Lulu and Nana, were conceived by in vitro fertilization in a couple whose father was HIV-positive. While still in the embryo state, the researcher used the CRISPR molecular scissors to remove a gene encoding a protein called CCR5. This is the main target of HIV, which uses it as a gateway to infect immune cells.

About 10% of the population of European origin has a mutation that eliminates the expression of CCR5, thus protecting it from infection with this virus. The goal of He Jiankui was to replicate this mutation and thus make these twins resistant to HIV for life.

This idea was not unfounded: two HIV patients went into remission in 2008 and 2013 after a bone marrow transplant of donors carrying this mutation, as part of treatment against leukemia.

However, according to a study published this week in the journal Nature Medicine (New Window) , this mutation does not bring benefits. It would even be linked to a decrease in longevity in people who carry it.

Although these results represent a correlation, and no mechanism that can explain it has yet been identified, they still highlight the risks that accompany experimental procedures whose full consequences are not known.

An unexpected effect

To evaluate the effects of a CCR5 deletion, researchers at the University of California at Berkeley analyzed the genetic and medical data of more than 400,000 Britons enrolled in the UK Biobank research project.

For the CCR5 mutation to affect HIV resistance, both the gene copy, both from the mother and from the individual’s father, must be affected by this mutation.

The researchers noted that, in people with two copies of the mutation, the mortality rate before the age of 76 was 16.5%, 21% higher than for people with the mutation only only copy of the gene or on none. Although subtle, this effect remains significant, and becomes detectable when analyzing the medical data of a large number of people.

These data, however, do not allow to know how this mutation leads to a decrease in longevity. Previous studies have shown that the disappearance of CCR5 makes people more susceptible to viruses like the flu. It is therefore possible that the loss of this gene also makes them more susceptible to other diseases.

For the researchers, these results do not mean that we must abandon the interest of CCR5 for the treatment of HIV, or the use of CRISPR for the treatment of diseases. However, they show that these benefits remain contextual, and that it is difficult to predict all the consequences that a deletion of genes can bring.

Uncertain consequences

This study also does not know what will happen to the twins on which the experiments of He Jiankui were conducted. According to the data presented in the days following his announcement, the researcher was not able to modify the gene as he hoped.

Not only have the modifications remained incomplete in both children, but they would not be the same for all the cells of their bodies, a phenomenon known as mosaicism.

These gene combinations mean that it is currently impossible to know how binoculars will be affected or whether other problems may occur during their lifetime.

Since these genetic modifications have been practiced in the form of embryos, it is possible, however, that these mutations are transmitted from one generation to the next.

In January, the Chinese government released a report that He Jiankui had acted outside the legal framework. He was also fired from his university. Meanwhile, his gesture has revived the debate on genetic modification of embryos, and pushed some researchers to ask for a moratorium on this technology.