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Human CRISPR

Biocentury has a roundup of reactions to the recent human CRISPR paper:

There’s no dispute that because the technology is in its infancy, much more work needs to be done to establish its safety. Stakeholders also agree that no experiments should be done, at least for now, in clinical programs that would involve modifying germline DNA and creating gene-edited embryos.
However one camp argues that research to understand the technology better and establish its safety in human cells should be permitted under appropriate regulatory controls. That means gene editing would be performed on human germline cells, but that any products would be discarded. Advocates for that position believe it’s worth considering whether there are therapeutic situations where using gene editing might be beneficial.
The other school of thought is that there will never be a justifiable use related to human germline cells, and that no experiments should be done for either research or clinical applications. The argument is not just that it’s a slippery slope from establishing safety and methods for well-meant therapeutic uses to providing a roadmap for eugenics.

Over the whole discussion, though, seems to be an air of “Well, someone’s going to be doing it; it’s just a matter of when”. That’s how I see it, and that makes the job how to have it happen in the least crazy way possible.

13 comments on “Human CRISPR”

  1. GCC says:

    I’m not surprised that someone has now tried CRISPR editing of human embryos and that there’s tons of hype about the potential of doing this, but ethical issues aside, I don’t even really understand why anyone would choose genome editing of human embryos over the much simpler and presumably less risky option of preimplantation genetic screening.
    I keep hearing people in the media talk about fixing errors in the genes for Huntington’s disease or cystic fibrosis in human embryos, but why wouldn’t you instead just screen for embryos without the disease-causing mutations?
    I do see therapeutic potential for genome editing of somatic cells for people with some diseases, especially ones affecting blood cells or other easily transplanted cells. And of course, CRISPR and other genome editing technologies will continue to be very, very useful in the lab to create model organisms and genetically modified cell lines. But for human embryos, I just don’t see a lot of upside to the technology.

  2. Anonymous says:

    As per 1: CRISPR is a prime example of scientists (and even investors) getting excited about technological possibilities without thinking about commercial realities. An over-engineered solution looking for problems.

  3. Anonymous says:

    I agree with the above comments however this research does make significant headway on a different front:
    Challenging our scientific ethics and value structure.
    The challenges that face the broad field of therapeutics (as well as others) are thought to be technological. However the social challenges of incorporating these technologies are the real barriers that prevent the R&D from getting done in the first place. I don’t believe CRISPR edited embryos are going to be in SkyMall anytime soon and perhaps they never will for the reasons 1 mentions, I’m glad these scientists have tried and failed. If the embryos and sperm were collected from willing participants free from coercion (monetary or physical) than I see no intrinsic ethical debacle. I’m sure that this view is not shared by many vocal opponents but hopefully it will help to push the debate out of the realm of religious and faith-based arguments and force genuine progress on our value and ethical systems if not our immediate therapeutic technologies.

  4. Bryan says:

    I agree with #1 that PGD is far superior to CRISPR for fixing genetic disease in embryos. However, where CRISPR is important is in the introduction of rare protective alleles. We’re not going to be able to modify traits like intelligence or height anytime soon, but there are some rare mutations that protect against disease. A particular mutation in the APP protein lowers one’s risk of Alzheimer’s disease and dementia later in life. Loss of function of PCSK9 lowers LDL levels and the risk of cardiovascular disease. Other mutations can render one immune to diseases like HIV or stomach flu. These modifications (if we get around the problem of off-target mutagenesis) would seem pretty safe since there are perfectly healthy people living today who carry these mutations. Perhaps one day, we’ll look at gene editing as having a role akin to vaccination in eliminating human disease. Given all the difficulties in finding a cure for Alzheimer’s, investigating gene editing of APP as a means of prevention may be a promising way of eliminating the disease.

  5. CS says:

    The debate about this is particularly disheartening. Since when does “someone will do it anyway” have any bearing on whether something is right to do?

  6. GCC says:

    Definitely valid points, Bryan, and your article that you linked your name to was very good. My main concern with the approach of introducing rare protective alleles is that since they are rare, have enough people with those variants been studied to know that there aren’t negative consequences? Yes, there are “perfectly healthy people” with those variants, but at the population level are they just as healthy as those with the more common alleles?
    I would guess that there are lots of genetic variants that reduce the risk of one disease and increase the risk of another (and variants that reduce the risk of a disease only in some genetic backgrounds and/or environments). We’d obviously need to make darn sure we know enough about the health of the people with the rare alleles before editing those variants into human embryos.
    Still though, it’s definitely an interesting concept and one that could be very promising down the road once the technology has matured. I wish this idea was getting more attention in the media, rather than the idea of fixing disease genes in embryos, which really doesn’t make much sense in the vast majority of cases.

  7. Bryan says:

    GCC hits on very important points. We don’t know enough about gene-gene and gene-environment interactions to know with certainty the effect of the rare protective mutations in other genetic backgrounds. That said, every natural pregnancy involves creating a unique combination of rare genetic variants and that process does not always produce a good outcome, so perhaps that is the suitable point of comparison. Still, testing will be needed, and that stands as the biggest obstacle. For example, if we started a clinical trial today to assess the safety and efficacy of the APP mutant in preventing Alzheimer’s, we wouldn’t know the answer until about 2100. I would hope we’d come up with some better treatment for Alzheimer’s before then.

  8. Anonymous says:

    I think we should certainly follow the second recommendation. It’s always safe to determine whether something is safe, and in order to learn those lessons we need to try to figure these things out.
    Because I’m pretty certain that safe and effective editing of human is possible, and things will really start to improve once that takes off. It’s up to us to figure out how to do it, and we can figure these things out safely.

  9. kjk says:

    Why not use chimpanzee embryos? Basically human from a biochemical perspective and less moral issues of tampering with human life.

  10. UMDFScience says:

    We need to also keep in mind the “other” genome- mitochondrial DNA. While still germline modification, we are only talking about ~0.1% of all genes and those are primarily focused on energy production. Diseases due to mtDNA mutations are not so easily addressed by PGD due to mito-specific traits such as copy number and heteroplasmy. Here gene editing techniques could absolutely play an important role in preventing the transmission of disease from mother to child.
    Additionally, mitochondrial replacement therapy is a very hot topic in IVF. Why edit the genes when you can replace the entire genome? Clinical usage has already been approved in the UK, but there remain safety and efficacy questions.
    Might the mitochondrial genome be the better proving ground for burgeoning gene editing techniques?

  11. Anonymous says:

    Wouldn’t it be cheaper and easier just to kill the diseased baby and make a new one? OK I meant “abort” rather than “kill” but same difference, the end result is the same.

  12. Morgrim says:

    Late in responding, but screening embryos isn’t always an option. There are some genetic diseases that are carried on dominant genes and a particular couple may not be able to produce an embryo that will lack it.
    (The only one I can think of offhand is a mutation that DRASTICALLY increases the likelihood and severity of cancer, and remains limited in the gene pool mostly because the majority of carriers will be dead or infertile before having two or more kids. The only ‘cure’ currently around is to not reproduce.)

  13. GCC says:

    Re: 12, people with a dominant mutation in a disease gene almost always have a second normal allele that could be passed on, so preimplantation genetic screening works in those cases too. Even if two people with dominant mutations in the same disease gene were to have kids, a quarter of them would still usually get two normal copies of the gene.
    There are people that are homozygous for dominant mutations in a disease gene and preimplantation genetic screening wouldn’t help them, but that’s extremely rare.
    (Many thanks to Reginald C. Punnett for helping me think through the possibilities!)

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