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Saturday, 8 February, 2025
HomeEthicsRisks and benefits of human genome editing unpacked in Australian study

Risks and benefits of human genome editing unpacked in Australian study

Scientists know about tens of thousands of DNA variants that are associated with human diseases. On their own, the vast majority of these variants have small effects. But taken together, the result can be substantial.

The effects of modifying multiple variants at once, known as polygenic genome editing, were the subject of an analysis published recently in Nature, with the study revealing that polygenic genome editing in human embryos could substantially reduce the likelihood of certain diseases occurring, but it raises concerns, not least the renewed threat of eugenics.

There are other caveats too, the researchers reported.

An editorial in Nature said the journal published this work because it was important to start a conversation about what could happen if more sophisticated gene-editing technologies become available, which could be the case within 30 years, the authors say.

Societies need to consider relevant benefits and risks before that day comes.

In the study, Peter Visscher, a statistician and geneticist at the University of Queensland, Australia, and his colleagues modelled the consequences of simultaneously editing specific variants linked to a number of diseases, including Alzheimer’s disease, schizophrenia, type 2 diabetes, coronary artery disease and major depressive disorder (MDD).

Gene-editing tools currently in development, called multiplex technologies, are projected in the coming decades to enable rapid precision DNA editing at tens, or even hundreds, of locations.

The researchers found that, in some cases, editing a single variant associated with a polygenic disease can have strong effects, and, with the exception of MDD, editing up to 10 genes associated with a disease can reduce its lifetime prevalence by an order of magnitude.

This would be a huge achievement.

However, the authors also include an extensive discussion of the study’s limitations and challenges. The fear that polygenic gene editing could be used for eugenics looms large among them, and is, in part, why no country currently allows genome editing in a human embryo, even for single variants.

There are also significant technical caveats. The authors say that polygenic editing is unlikely to benefit the wider population in any realistic timeframe, because the technology is available only through in vitro fertilisation.

There are also not yet enough known causal variants for common diseases.
Other limitations to the findings include the fact that many diseases are also caused by non-genetic factors, which are harder to model.

Furthermore, a successful new treatment for one of the diseases is likely to reduce the need for human genome editing. There are also pleiotropic effects to consider: a gene variant that is a risk factor for one disease could offer protection against another. And then there’s the risk that these technologies will widen inequality and social divisions, because the costs will probably be substantial.

These issues need society-wide discussion.

The past few decades have shown that new technologies are being developed ahead of conversations on their ethics or social and environmental impacts. From the atomic bomb to artificial intelligence, discussions of risks, benefits, safety, regulation and transparency have had to play catch-up.

As recently as 2018, biophysicist He Jiankui shocked the world by announcing that he’d created genetically-edited babies. The mistake should not be repeated.

Although it will be some decades before human-gene-editing science and technologies can be applied with precision and at scale, they are on their way; this is not a hypothetical issue. The intervening time should be used wisely.

Societies need to be ready, understand the upsides and the dangers, and know what to do when that time comes.

Study details

Heritable polygenic editing: the next frontier in genomic medicine?

Peter Visscher, Christopher Gyngell, Loic Yengo & Julian Savulescu .

Published in Nature on 8 January 2025

Abstract

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases. In this Analysis, we show that polygenic genome editing could theoretically yield extreme reductions in disease susceptibility. For example, editing a relatively small number of genomic variants could make a substantial difference to an individual’s risk of developing coronary artery disease, Alzheimer’s disease, major depressive disorder, diabetes and schizophrenia. Similarly, large changes in risk factors, such as low-density lipoprotein cholesterol and blood pressure, could, in theory, be achieved by polygenic editing. Although heritable polygenic editing (HPE) is still speculative, we completed calculations to discuss the underlying ethical issues. Our modelling demonstrates how the putatively positive consequences of gene editing at an individual level may deepen health inequalities. Further, as single or multiple gene variants can increase the risk of some diseases while decreasing that of others, HPE raises ethical challenges related to pleiotropy and genetic diversity. We conclude by arguing for a collectivist perspective on the ethical issues raised by HPE, which accounts for its effects on individuals, their families, communities and society.

 

Nature article – We need to talk about human genome editing (Open access)

 

Nature article – Heritable polygenic editing: the next frontier in genomic medicine? (Open access)

 

See more from MedicalBrief archives:

 

Slippery slope when gene editing advances outpace the law

 

Gene-editing researchers jailed over illegal medical practices

 

Call for guidelines and ethical boundaries in genetic editing therapies

 

CRISPR gene-editing improves vision in blind children – US trial

 

US gene-editing research offers hope for progeria

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