Making dozens of changes to people’s DNA could dramatically extend their healthy lifespans, according to the first study to try to quantify the potential benefits of editing egg and sperm cells – called .
“This research shows that we could potentially use germline gene editing to make us all resistant to diseases of old age,” says biomedical ethicist Christopher Gyngell of the University of Melbourne, Australia, who was not involved in the study.
It is already possible to prevent genetic diseases caused by single mutations, such as cystic fibrosis, by screening. For instance, IVF embryos can be screened before implantation.
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But every one of us carries many thousands of gene variants that do not inevitably lead to particular diseases but do affect our risk of developing them. Changing a single one would make little difference, but changing many might. This cannot be achieved by screening but might become possible in the next few decades, says Roman Teo Oliynyk, a computational biologist at the University of Auckland, New Zealand. For instance, the CRISPR genome editing technique has already been used to make multiple changes to the genomes of animal egg cells.
Risk score
Oliynyk looked at gene variants known as SNPs that affect the risk of diseases of old age, including heart disease, stroke, type 2 diabetes, Alzheimer’s, osteoarthritis and some cancers. By looking at which variants an individual has, it is possible to estimate whether they have a greater or lower risk of developing these diseases – known as a polygenic risk score.
Oliynyk modelled what would happen if individuals with a higher-than-average risk had undergone genome editing before birth to reduce their risk to the average. Achieving this would require altering dozens of SNPs on average, and hundreds in those with the highest risk. But the results would be dramatic, his findings suggest, with people on average living many years or even decades longer before developing these diseases.
The benefits would be greatest for cancers. Those treated would live two decades longer on average before developing breast, prostate or colorectal cancers, and their lifetime risk would be more than halved even assuming they live 10 years longer. “Cancers on the model show a very significant and lasting improvement,” says Oliynyk.
Assumptions
However, as Oliynyk acknowledges, his conclusions depend on several assumptions. One is that we have correctly identified SNPs that affect disease risk. In reality there is still huge uncertainty. “I don’t think we are there yet, and I’m not sure we ever will be,” says geneticist Helen O’Neill of University College London.
She points out that the effect of gene variants can depend both on the environment and other gene variants. In a rapidly changing world where different populations are intermingling, it may be impossible to accurately predict risks and benefits.
Another assumption is that altering SNPs has no side effects, says Ali Torkamani of the Scripps Research Translational Institute in La Jolla, California. “There is often a trade-off to be had – you’ve reduced your risk for coronary artery disease but you may have increased your risk for some other disorder,” he says. “It’s unrealistic to assume that there is none.”
There’s also a major practical problem, says O’Neill. You can’t know what SNPs an embryo will inherit until it has formed, so you cannot work out risk scores in advance. But if you have to wait to this stage, it may be too late to edit the genome.
Olinyk thinks the answer could be synthetic genomes – rebuilding genomes from scratch and correcting the disease-causing variants along the way. This is not yet possible with large genomes like ours, but Olinyk is confident it will be one day. “It is a purely technological issue, and these are always solved.”
biorXiv
