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Embryos donated to science blow the whistle on CRISPR
The controversial gene-editing technique mis-snips again. And thanks to embryos donated to science, we know about it.
Many people, finding themselves at the end of their reproductive journey, decide to donate their extra embryos "to science." We don't hear all that much about what becomes of these embryos — what scientific advancements they enabled, what policies they influenced, what practices they helped to curtail.
Here is one such story.
Twenty-five embryos were volunteered into a study using CRISPR, a controversial gene-editing technique. (For a bit of background on the science and politics of CRISPR, see this round-up.) All the couples who donated their embryos gave informed consent. They were told about the research project, were given an opportunity to receive counselling about their decision, and agreed that any results from their contribution could be published in scientific journals. No money changed hands for the embryos.
Some of the findings generated by studying these embryos ended up in one of the world's most prestigious scientific journals, Nature, in this study about the role of a particular gene (POU5F1) in early embryological development.
But those embryos went on to play a role in a second study as well — a sort of post-mortem on the first. The DNA was reprocessed and the data were reanalyzed. The second study examined whether CRISPR had snipped out the gene of interest as accurately as desired. One of the concerns about CRISPR is that it might not edit precisely enough, deleting bits from places we want them, and adding bits in places we don't. Mistakes are especially hard to detect when they're almost right, but not quite.
Kathy Niakan, at the Francis Crick Institute in London, UK, (the senior author on both papers) and her colleagues, were not the first to ask about this issue or to examine it. But in this study they used a sophisticated method of analysis that allowed them to identify DNA damage that would have been missed by previous methods.
Eighteen of the embryos had been CRISPRed, and seven had been used as controls. Of the 18, the researchers found, eight showed abnormalities on the chromosome where the target gene resided, and four of those abnormalities were right next to or even within the target area. By contrast, only a single control sample had an abnormality and it was not near the target site.
This is important, because it shows that CRISPR may be making even more errors than we realize. They may be easy to miss. And they could be consequential.
"Altogether, this points to the need to develop a robust technique to distinguish cells and embryos affected by CRISPR-Cas9 unintended damage from correctly edited embryos," the authors write. Also: "Our re-evaluation of on-target mutations, together with previous accounts of unexpected CRISPR-Cas9 on-target damage... strongly underscores the importance of further basic research..."
The paper came out earlier this month in a publication known as bioRxiv, a place where research can be viewed before it's been fully scrutinized by fellow scientists. So it's possible that peer review will call attention to some flaw in how the work was done or how the conclusions were drawn. But for now the findings should at least make us cautious.
If you don't feel inclined to read the full scientific paper, consider reading the excellent summary, "Scientists Edited Human Embryos in the Lab, and It Was a Disaster," by Emily Mullin. Among the experts she quotes is Fyodor Urnov, at the University of California at Berkeley, who says, "This is a restraining order for all genome editors to stay the living daylights away from embryo editing."
None of the embryos in the study were intended to develop into babies, and they did not grow in the lab for more than 14 days.
Parents who have extra embryos after completing their families are asked to make excruciating decisions about what to do with them. Some decide to donate to science. Despite all my support of scientific research, I'm not sure I'd have the strength to do that. But thanks to the families who do, we have important findings like these.
Gregorio Alanis-Lobato et al. "Frequent loss-of-heterozygosity in CRISPR-Cas9-edited early human embryos."bioRxiv. 2020.
Emily Mullin. "Scientists Edited Human Embryos in the Lab, and It Was a Disaster." OneZero. 2020.
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