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posted by Fnord666 on Wednesday September 13, @10:32AM   Printer-friendly
from the crisper-eggs dept.

Skepticism surfaces over CRISPR human embryo editing claims

When the first U.S. team to edit human embryos with CRISPR revealed their success earlier this month, the field reeled with the possibility that the gene-editing technique might soon produce children free of their parents' genetic defects. But the way CRISPR repaired the paternal mutation targeted in the embryos was also a surprise. Instead of replacing the gene defect with strands of DNA that the researchers inserted, the embryos appeared to use the mother's healthy gene as a template for repairing the cut made by CRISPR's enzyme.

But such a feat has not been observed in previous CRISPR experiments, and some scientists are now questioning whether the repairs really happened that way. In a paper published online this week on the preprint server bioRxiv, a group of six geneticists, developmental biologists, and stem cell researchers offers alternative explanations for the results. And uncertainty about exactly how the embryos' DNA changed after editing leaves many questions about the technique's safety, they argue. (The authors declined to discuss the paper while it's being reviewed for publication.)

Embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, who led the now-disputed experiments, released a statement saying that his team stands by its explanation. "We based our finding and conclusions on careful experimental design involving hundreds of human embryos," it says.

[...] Although the researchers inserted short strands of DNA as templates for repair, the cells didn't seem to take them up; those specific sequences were absent from the embryos. The cells must have relied instead on the nonmutated sequence in the egg donor's DNA when making the repairs, the team concluded.

The bioRxiv response, led by developmental biologist Maria Jasin of Memorial Sloan Kettering Cancer Center in New York City and Columbia University stem cell biologist Dieter Egli, challenges that interpretation. The authors, which also include well-known CRISPR researcher and Harvard University geneticist George Church, say that the Nature paper goes against conventional wisdom about how embryos are organized early in development. Right after an egg is fertilized, the DNA from the sperm and the egg aren't believed to be in close enough proximity to interact or share genes, they explain.

Previously: First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success
U.S. Human Embryo Editing Study Published

Study in question: Correction of a pathogenic gene mutation in human embryos (open, DOI: 10.1038/nature23305) (DX)


Original Submission

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First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success 28 comments

U.S. scientists have genetically modified human embyros using CRISPR and have apparently avoided the worst of the off-target effects that have plagued previous efforts. The results are unpublished and the team is not commenting yet:

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, Technology Review has learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

Also at STAT News.

Previously: Chinese Scientists Have Genetically Modified Human Embryos
NIH Won't Fund Human Germline Modification
Group of Scientists and Bioethicists Back Genetic Modification of Human Embryos
The International Summit on Human Gene Editing
UK Scientist Makes the Case for Editing Human Embryos
Second Chinese Team Reports Gene Editing in Human Embryos
Scientists Keep Human Embryos Alive Longer Outside of the Womb
Francis Collins Retains Position as Director of the National Institutes of Health


Original Submission

U.S. Human Embryo Editing Study Published 21 comments

The human embryo editing study first reported by MIT Technology Review last week has been published in Nature. Scientists led by the Oregon Health & Science University's Shoukhrat Mitalipov edited human embryos to remove the MYBPC3 mutation associated with hypertrophic cardiomyopathy:

The experiment corrected the defect in nearly two-thirds of several dozen embryos, without causing potentially dangerous mutations elsewhere in the DNA.

None of the embryos were used to try to create a baby. But if future experiments confirm the techniques are safe and effective, the scientists say the same approach could be used to prevent a long list of inheritable diseases. "Potentially, we're talking about thousands of genes and thousands of patients," says Paula Amato, an associate professor of obstetrics and gynecology at Oregon Health & Science University in Portland. She was a member of the scientific team from the U.S., China and South Korea.

[...] Amato and others stress that their work is aimed at preventing terrible diseases, not creating genetically enhanced people. And they note that much more research is needed to confirm the technique is safe and effective before anyone tries to make a baby this way. But scientists hoping to continue the work in the U.S. face many regulatory obstacles. The National Institutes of Health will not fund any research involving human embryos (the new work was funded by Oregon Health & Science University). And the Food and Drug Administration is prohibited by Congress from considering any experiments that involve genetically modified human embryos.

Nevertheless, the researchers say they're hopeful about continuing the work, perhaps in Britain. The United Kingdom has permitted genetic experiments involving human embryos forbidden in the United States. "If other countries would be interested, we would be happy to work with their regulatory bodies," says Shoukhrat Mitalipov, director of the Oregon Health & Science University's Center for Embryonic Cell and Gene Therapy.

Also at NYT, MIT, BBC, Science Magazine, and Scientific American.

Correction of a pathogenic gene mutation in human embryos (open, DOI: 10.1038/nature23305) (DX)

Previously: First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success


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  • (Score: 2, Interesting) by Anonymous Coward on Wednesday September 13, @10:44AM

    by Anonymous Coward on Wednesday September 13, @10:44AM (#567163)

    They damaged the DNA of the mutant zygotes leading to selective death of those cells and an increase in the proportion of WT zygotes... https://soylentnews.org/comments.pl?noupdate=1&sid=20891&page=1&cid=548521#commentwrap [soylentnews.org]

  • (Score: 0) by Anonymous Coward on Wednesday September 13, @02:16PM (2 children)

    by Anonymous Coward on Wednesday September 13, @02:16PM (#567226)

    "...CRISPR’s cuts can sometimes cause chunks of DNA to be removed from the strand before the two cut ends are rejoined, they note. That would mean no detectable mutation—but it could also mean missing sections of DNA that could have unknown consequences for the embryo."

    Can CRISPR not be used on other mammals? say mice, if this sort of thing can happen seems like it might be a good idea to do some testing on embryos you can actually allow to develop to see how it works out before you start trying it on humans

    • (Score: 3, Interesting) by Immerman on Wednesday September 13, @03:18PM (1 child)

      by Immerman (3985) on Wednesday September 13, @03:18PM (#567244)

      Well, it could give you a clue, but just because it has no effect in mice doesn't mean it won't do something horrible to humans. And vice-versa of course. DNA expression can vary quite a bit between species.

      There also seems to be something missing - my understanding is that CRISPR slices out a targetted segment of DNA, and then replaces it with it's payload. You don't just add some extra DNA strands as templates that get used by the cell for repair, CRISPR "welds in" your replacement.

      If something else is going on, then that should be a huge red flag that either the researchers aren't actually doing what they're claiming, or that our understanding of CRISPR is woefully inadequate.

      • (Score: 0) by Anonymous Coward on Wednesday September 13, @09:24PM

        by Anonymous Coward on Wednesday September 13, @09:24PM (#567477)

        All CRISPR/cas-9 does is (preferentially) cut (introduce double strand breaks) at a certain target sequence. Once this happens, either
        A) The cell dies
        B) The break is fixed via NHEJ (non-homologous end joining), in which random errors will be found at the splice
        C) The break is fixed via HDR (homology-directed repair), in which a DNA sequence with ends that overlap the cut ends is copied and inserted

        It is important that A, B, and C are all done by enzymes/etc already present in the cell (the repair/death is "natural", only the cut is "artificial"). Before "gene editing" became a big deal it was commonly accepted that A >> B >> C for most systems, where ">>" indicates 10x - 1000x more likely. For studies like this, they largely ignore A and choose instead to come up with byzantine explanations for the strange results they get. In this case it appears the researchers were not familiar enough with developmental bio to anticipate critiques, so their explanation was deemed implausible.

        The debunking here doesn't seem that convincing to me either though... instead it seems that the CRISPR/cas-9 material that gets in the cells can stay active through multiple cell divisions, so whatever is going on immediately after fertilization doesn't really matter.

  • (Score: 3, Interesting) by leftover on Wednesday September 13, @02:57PM (1 child)

    by leftover (2448) on Wednesday September 13, @02:57PM (#567238)

    Although this might just be a matter of my own shallow reading of TFP, there seems to be something missing, specifically a way to definitively measure and record the results. Having such capabilities would be nice for experiments that are Editing. Human. DNA. Car analogy: if you are building a race car, you don't test "crossing the finish line" first.

    --
    Bent, folded, spindled, and mutilated.
    • (Score: 0) by Anonymous Coward on Thursday September 14, @06:43AM

      by Anonymous Coward on Thursday September 14, @06:43AM (#567674)

      Actually human embryo editing doesn't deserve much of anything including funding. There really isn't that much benefit to this technology for the stated purpose.

      It's easier to detect flaws than to fix them. So just abort the embryos with the flaws. If your genes are so crap that you keep producing significantly faulty embryos then perhaps you shouldn't breed. There are already 7+ billion people on this planet so you should have to come up with a good reason why your provably crappy genes need to be reproduced albeit with some of the really crap bits removed.

      If you think crappy genes are worth reproducing why not use mine instead? They're still crap (there's a reason why I'm an asshole) but they don't have your really crap genes.

      You complain it won't be similar enough to your genes? Don't lots of (silly) people say there's no difference between blacks, whites, asians? ;)

      As for the other purposes like "improvements", the stuff like "unauthorized reproduction" and worse come to mind.

  • (Score: 0) by Anonymous Coward on Wednesday September 13, @03:52PM

    by Anonymous Coward on Wednesday September 13, @03:52PM (#567258)

    There are a bunch of companies fighting over the CRISPR patents, I'm gonna go with get ready for a ton of junk unrepeatable studies that confuse everyone with there results but will be used in the patent battle

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