Weekend Edition.

Editing humans.

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News Items is “the most valuable newsletter out there.” — Peggy Noonan.

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1. The Economist:

One of the greatest scandals in modern science began with a late-2010s advertisement for HIV-positive couples looking to have children through in-vitro fertilization (IVF). The ad had been put out by a scientist named He Jiankui, a biologist then at the Southern University of Science and Technology in China. Several pairs responded. For each couple, Dr He and his team harvested their sperm and eggs and created embryos through IVF. He edited a gene in each embryo using CRISPR, then did something that had never been done before: had the edited embryos implanted into the women’s wombs.

The gene, CCR5, is responsible for a cell-surface protein which plays a key role in HIV infection. A natural variant of CCR5 blocks production of the protein and confers protection against HIV. It was this protection that Dr He sought to give the embryos. In November 2018, just before the second International Summit on Human Genome Editing, MIT Technology Review reported both that the experiments had taken place and that two of the embryos had, when implanted in the womb, resulted in successful births. As a result there were now two little girls with edited genomes.

At the summit, Dr He appeared unprepared for the uproar that followed. His colleagues, who considered such experimentation premature and unsafe, were outraged. Slowly it became clear that not only did Dr He’s work have technical failings, but also he had broken the rules within which scientists must operate.

But underneath the outrage lay long-running concerns about the fundamental concept of editing embryos. Edits which take place that early in the developmental process are passed on to every other cell as the embryo grows, including the “germline” cells that will eventually produce sperm or eggs. If nothing is done later to reverse them, they will thus be passed on down the generations—unlike the sort of CRISPR edit that cures a disease in someone already born. By definition future generations cannot give their informed consent to a procedure that takes place long before they are conceived. For that reason embryo editing is in effect banned in 27 EU member states under the Oviedo Convention. (Many other countries, including Britain and Canada, also legally forbid the practice.)

The main attraction of embryo editing is that it allows edits which are very difficult or impossible later on. When editing a person who has already been born, some tissues, such as the brain, are very hard to reach. Embryo editing does not have that problem, as all the cells that go on to form the organs will in theory carry the edit. There are also people who think passing on an edit is not such a bad thing. Families in which successive generations have battled the same genetic disease often wish to spare their descendants the same fate, says Dagan Wells, a reproductive biologist at the University of Oxford (he is agnostic on the procedure).

In January 2025 a paper appeared in Nature discussing the societal benefit of polygenic embryo editing—that is, making several edits in the same embryo. Rather than just curing genetic diseases, it could tweak multiple genes that together alter the risk of conditions like Alzheimer’s disease or diabetes. The authors, led by Julian Savulescu, an Australian philosopher, acknowledged that the concept is speculative but suggested that it could dramatically benefit those who are edited. But what about those who are not edited?

The question of precisely who gets edited, and for what purpose, cuts to the heart of concerns around germline editing. Families struck by a genetic disease probably would benefit but they are in relative terms a fairly small group. Many will be interested in enhancements that polygenic embryo editing could offer. At first that might mean adding protection for preventable disease. But eventually it could mean tweaking traits like appearance and intelligence—in other words, creating designer babies. Some worry the rich would edit their offspring “better” and that people with disabilities or who are simply average would be put at greater disadvantage. “Gene-editing techniques applied to non-disease traits may deepen inequalities and raise the specter of eugenics,” argued Dr Savulescu and his team in their paper.

Others think it is far from clear that edited people will indeed benefit. A genetic variant that is advantageous in one context may be bad in another. The variant of CCR5 that protects against HIV, for example, has been linked to an increased risk of complications and even death during other infections. These unknowns are worth worrying about, argues Hank Greely, a lawyer at Stanford University and the author of the book “CRISPR People: The Science and Ethics of Editing Humans”. His main objection to Dr He’s CCR5 project was that its risk-benefit ratio was unacceptable: the benefits, if there were any, would be limited, and the risks, both any which were known and those yet to be understood, were potentially substantial. Dr He, who is out of prison and apparently back in a laboratory—the sources of his funding as yet unclear—is unfazed by this ignorance. His new germline project focuses on a rare variant found in Icelanders which protects against Alzheimer’s, though he has promised not to create any more pregnancies. (Source: economist.com)

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2. The Economist:

CRISPR might be on the cusp of transforming medicine and agriculture, but in research things have already changed. Almost 9,000 scientific papers mentioned CRISPR tools in their abstracts in 2024, up from 300 in 2013. Since 2012 Addgene, a non-profit repository of DNA reagents, has shipped more than 300,000 CRISPR preparations to 5,000 organizations in around 100 countries. “You can just simply order everything you need,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. CRISPR RNA is about as hard to get as the pizzas researchers order when working on gene editors into the night. (Source: economist.com)

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3. Bloomberg: