Gene edited twins run risk of early mortality

06 June 2019

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CRISPR gene edited twins have been found to have a 21% higher mortality rate before the age of 76. The bombshell experiment to edit these twins was announced on the 25th of November 2018, where a team led by Chinese scientist Jiankui He at the Southern University of Science and Technology recruited couples that were willing to create the first gene-edited babies. These twins were the only successful experiment of seven conducted to create babies that are resistant to the HIV infection. By editing a gene known as CCR5 with CRISPR-CAS9, a powerful tool that allows scientists to alter DNA sequences and modify gene function, the team was able to obstruct the HIV infection’s ability to cling to the twins’ cells leading to a lower risk of infection.
 
“You can think of HIV, maybe, as a boat that’s floating around, it’s looking for a place to dock. This gene product, this protein, provides a place for the ‘boat’ to dock” explains Dr. Florian Merkle from the Institute of Metabolic Science in Cambridge, commenting on the study.

In this recent study published in Nature Medicine, Drs Xinzhu (April) Wei and Rasmus Nielsen from the University of California Berkeley used the death register information of over 400,000 individuals of British descent to investigate the possible repercussions of the CCR5 gene mutation imposed by He. He’s initial goal was to alter the twins’ CCR5 gene to mimic a naturally occurring European mutation that is directly related to the protection against HIV, called CCR5 - Δ32, as it does not allow the virus to cling to the host’s cells and destroy them. The UK Biobank led scientists to find that those who had two mutated copies of the gene between the ages of 41 and 78 had a higher death rate than compared to those with only one or no mutated copies.

CCR5 is a gene that is found in all humans and most animals. He’s decision to remove, or inactivate, a gene with such influence is bound to come with consequences. Past studies have linked the higher death rate of two mutated copies of CCR5 to the influenza infection. Once the influenza virus had been contracted, the individuals with the gene mutations had a fourfold increase in mortality. Due to the vast number of body functions the gene is involved with though, the association to influenza mortality is not definitive. Despite the ambiguity of the science and the small amount that is understood in gene editing, He still decided to conduct his experiments.

“Really this is something that everyone was afraid might happen by somebody. And it seems like the real reason was not to really provide any benefit to these children, but to prove that he could do this and that he would be the first one to actually do this” mentions Merkle.

CCR5 is not all bad news though, there are also links to increased survival after stroke, protection against smallpox, and protection against flaviviruses which are a group of viruses including Zika and West Nile. Despite the associated benefits of the CCR5 gene, the field of potential unintended effects from genetic mutation is too complex for caution to be neglected. To even consider mutating human DNA, let alone actually doing it, is not a task that can be made hastily and will remain that way for some years to come.

“I think this really highlights the fact that there’s so much of biology that we have left to discover,'' cautions Merkle.“That there’s a real hazard in tinkering with what we don’t know in altering the human genome”

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