Genetically engineered CRISPR babies could live shorter lives

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The CRISPR gene modification technique offers major benefits to humanity, but scientists do not think the field is mature enough to allow large scale modification.
For this reason, when Chinese scientist He Jiankui changed the genes of two babies for them to resist HIV, his work provoked outrage.
A new study of 400,000 genetic profiles reveals that it has had an unexpected consequence.

Since Frankenstein, scientists were keen to prevent the public from having the impression of playing God. This is partly why the scientific community reacted so strongly to the announcement made by the Chinese biophysicist He Jiankui in 2018 that he had genetically modified the embryos of two girls in order to make them more resistant to HIV. Because of his work, he was fired from his position and could be subject to criminal prosecution.

Now, new research published in Nature Medicine underline the reason for this reaction. The study examined a database of genetic profiles of more than 400,000 people in the UK, focusing on those who had the delta-32 mutation to the CCR5 gene. When an individual inherits delta-32 of both parents, they have a strong resistance to HIV – it is the same mutation that he introduced in two subjects known by their pseudonyms, Lulu and Nana, using the technique CRISPR gene modification.

HIV resistance is a clear benefit of this mutation, but the problem with gene editing is that it can be extremely unpredictable. "It's way too premature," said Eric Topol, director of the Scripps Research Translational Institute in California. "We are dealing with the use of a human being – it is a big problem." New research has shown that this alteration has unintended consequences: individuals with this genetic mutation live two years less than those who do not.

Play with fire

ANTHONY WALLACE / AFP / Getty Images

He Jiankui at a round table after presenting his findings at the Second International Summit on Human Genome Modification in Hong Kong.

He selected Lulu and Nana for gene editing because their father was HIV-positive. It is much more common for HIV to go from mother to offspring, but it is possible, though rare, for HIV to pass from father to offspring. Provide Lulu and Nana each with two copies of delta-32 the mutation probably protected them against this possibility and against HIV later in life.

However, there is evidence that individuals with two copies of delta-32 catch flu, West Nile virus and some other diseases more easily. Although HIV is a serious disease, these diseases, which are much more common, can often be just as deadly, especially in old age. This is precisely the result that researchers have discovered in their analysis. Individuals with two copies of delta-32 20% were more likely to die before the age of 76, with the highest probability of death occurring at age 74.

In addition, since the genes of Lulu and Nana were modified while they were embryos, this mutation will be passed on to their offspring later. Given this scope, the reasons scientists have reacted with such horror are becoming clearer: The editing of genes on an embryo could have unintended and long-lasting consequences that could seriously affect what would have been healthy for generations.

Another unknown potential impact that delta-32 could have been related to the ethnicity of girls. The mutation is much more common in individuals from northern Europe, whereas it is very rare among individuals from Asia and Africa. Some researchers argue that the presence of delta-32 among Europeans is due to the impact of the epidemics of the Middle Ages, such as the Black Death. The absence of this mutation in other parts of the world is likely because it is simply not useful there – different environments have different diseases, against which delta-32 could be more deleterious than beneficial.

His actions and studies such as this highlight the importance of an intelligent and evidence-based regulatory framework for gene editing technologies. One question that we need to address is whether germline modification, such as that performed on Lulu and Nana, should be allowed, as these changes can be passed on to subsequent offspring. We also need a way to measure the impact of modifying specific genes so as not to surprise us with unwanted side effects, such as reduced life expectancy caused by delta-32. Overall, this study and its work show us that there are simply too many moving elements to simply introduce genetic mutations and see how things go. We must be more rigorous than that.