Is it progress when a self-aggrandizing mad scientist performs a reckless experiment?


Does this look like your idea of a mad scientist?

China is racing ahead in human biotechnology — it really helps when you can disregard ethical concerns altogether. It especially helps when you pay lip service to bioethics while simultaneously carrying out a major research program that directly contradicts the ethical concerns you’re piously declaiming.

There is a heroic history of scientists engaging in self-experimentation. The example that comes to mind is Barry Marshall, who drank down a solution of Helicobacter pylori to prove that the bacteria was the causal agent behind stomach ulcers. No research review committee would have approved such an experiment, but it paid off in that he won the Nobel for it. He also made himself very sick. It was a dramatic and rather stupidly dangerous gesture — there are safer ways to evaluate pathogens, and we drill safety into our students all the time.

Maybe we’re wrong. Maybe we should be encouraging students to lick random slime they find on the lab benches. We might lose a few, but the tiny percentage who discover brand new drugs or new diseases will make the deaths worthwhile, right?

But that’s self-experimentation. The new era of gene editing really is meaningless when done on yourself. It’s got to be done on embryos, on someone else. Is modifying genes in some other helpless, innocent person still heroic, or even heroically stupid? I don’t think so. We’re at the stage where experimentation on human cells is important, but the ethical guidelines don’t allow you to grow up that blastocyst to birth, because at that point you have a person who did not consent to the manipulation, and they have to live their whole life with the consequences of your tinkering.

That didn’t stop He Jiankui from launching a research program in which he genetically modified IVF embryos with Crispr, implanted them back in their mothers, and then cheerfully announced when the first of them gave birth.

There are more than a few problems with this experiment.

  • We don’t know all the limitations of Crispr yet. He assures everyone that there were no spurious modification of the genome in this case. Were there other cases, though? Do we trust that failures would be reported?
  • The entire purpose of this modification was prophylactic. They knocked out a component of the immune system that HIV uses to infect cells, presumably giving the child resistance to AIDS. Was this a pressing need? The child did not have a disease, they deleted a molecule to make it less likely they would get a disease. (The father is HIV-positive, so there was greater risk of exposure…but how much fluid transfer were the parents expecting?)

  • The deleted gene is CCR, which provides a kind of latch between T cells of the immune system and antigens. Most humans have CCR, a small percentage do not, and they have a greater resistance to some specific pathogens. But are there trade-offs? Are they more susceptible to other pathogens, or does it generally weaken the immune response? We don’t know, but hey, maybe now there will be a bunch of kids in China who will have genetically engineered weaknesses!

  • The experimenter had rushed a paper on bioethics to publication before this conference where he announced his result. The paper states that this kind of experiment is unethical.

    On Monday, He and his colleagues at Southern University of Science and Technology, in Shenzhen, published a set of draft ethical principles “to frame, guide, and restrict clinical applications that communities around the world can share and localize based on religious beliefs, culture, and public-health challenges.” Those principles included transparency and only performing the procedure when the risks are outweighed by serious medical need.

    He was actively pursuing controversial human research long before writing up a scientific and moral code to guide it.“We’re currently assessing whether the omission was a matter of ill-management or ill-intent,” says Barrangou, who added that the journal is now conducting an audit to see if a retraction might be warranted. “It’s perplexing to see authors submit an ethical framework under which work should be done on the one hand, and then concurrently do something that directly contravenes at least two of five of their stated principles.”

    It’s true. Patent dishonesty ought to be a good reason to pull a paper.

  • He doesn’t seem to be particularly aware of the limitations of genetics.

    He appeared to anticipate the concerns his study could provoke. “I support gene editing for the treatment and prevention of disease,” He posted in November to the social media site WeChat, “but not for enhancement or improving I.Q., which is not beneficial to society.”

    OK, I’ll bite. What genes for “improving IQ”? It’s easy to say you won’t do experiments on a gene that doesn’t exist, or involves modifying a very large number of mostly unidentified genes. I also don’t believe him. Of course improving intelligence would be beneficial to society — we try to do that all the time, it’s called education. If he had a target gene that was associated with greater intelligence, you know he’d be recruiting volunteers to do the study right now, which he’d carry out surreptitiously until he got a positive result that he could highlight at a major conference.

  • The lack of transparency while the experiment was ongoing is deeply troubling. If you don’t let people be aware of and monitor your potentially risky experiment, it’s too easy to literally bury (or cremate) results that you don’t like. It’s like p-hacking, where in this case the “p” stands for “people”.

  • This guy is a biophysicist and bioengineer. He is not qualified or trained in any way to assess ethical risks, but heck, we all know that the magic words “physicist” and “engineer” make one all-knowing, confident, and wise. I can only dream of having the degree of certainty that would allow me to publish a paper in a complex field which I know nothing about, and where my actual work flouts everything I say others should do. But then, I’m not a physicist.

I also have to add that this is not a particularly radical experiment. Crispr is now an established technique, and these sorts of experiments have been carried out in experimental animals. The only thing novel about it is that he rushed to execute an experimental technique, developed by other, more careful scientists, on a different experimental animal, human children. I expect there will be a day when gene editing on embryos is done to improve the quality of life for human beings, but that day doesn’t seem to be here yet, and reckless experiments don’t bring it any closer.

Comments

  1. rcs619 says

    Unfortunately this kind of thing was inevitable with China. They’re a repressive authoritarian state with a surplus of people and a just a lack of ethics across the board. They’re also all about big, headline-grabbing propaganda events, which this also serves as. The thing that concerns me is that that might want to test out this modification at some point. You’ve got a handful of babies that are supposed to be immune to HIV/AIDS. It seems like the next logical step if you’re an ethically dubious authoritarian state is to try and give those babies HIV at some point in their lives to see what happens.

    Like, I’m all for the eventual genetic improvement of the species. There are a lot of diseases that we could gradually erase from the human genome with this kind of technology, not to mention potential techniques to give us longer lives or just make our later years more pleasant. This kind of shit though is what’s going to end up pushing genetic engineering back years when it goes bad though, and when you’ve got totalitarian states shooting from the hip, trying to be the first out of the gate, it’s going to go bad. Then again, there’s also the chance that if it does, they’d just disappear everyone involved and we’d never hear about it.

  2. KG says

    Unfortunately this kind of thing was inevitable with China. They’re a repressive authoritarian state with a surplus of people and a just a lack of ethics across the board. They’re also all about big, headline-grabbing propaganda events, which this also serves as. – rcs619@1

    True enough, but in this case He’s university has suspended him without pay and announced an investigation, the deputy minister for science and technology has said the experiment was illegal under Chinese law, and hundreds of Chinese scientists have condemned it.

  3. imaginggeek says

    Are they more susceptible to other pathogens, or does it generally weaken the immune response? We don’t know…
    While your overall criticism is valid and I agree with it, this part is not valid – we have a very good idea of what CCR5 deficiency does as there are a number of people who are naturally null for the gene who’ve been investigated in great depth.

    Long story short, they are resistant (but not totally immune) to HIV infection, and if infected, have slower disease progression that CCR5 expressing individuals. Its been proposed that the null allele arose in response to Yersinia or smallpox, with cell culture and animal data providing some evidence the null allele does provide some protection from these pathogens.

    But there is a big downside – individuals homozygous for null allele are more susceptible to some viral infections – including a 4-fold increase in mortality from the flu – and may experience more severe pathology to other pathogens due to dysregulation of the immune system.

    So these kids (assuming this isn’t a false claim) may be somewhat resistant to HIV, but in exchange they’re more susceptible to several more common diseases.

  4. says

    Most of the history of human medicine has been characterized by experimenting on humans. Often without their understanding (or even permission). I’m not saying that’s right; but it’s how we got here.

  5. petesh says

    @1: Given the response by, to name but a few, the Deputy Minister of Science and Technology, the Chinese Society for Cell Biology, Genetics Society China & Chinese Society for Stem Cell Research, the Southern University of Science and Technology, China’s National Health Commission, the Shenzhen medical ethics committee, and the Guangdong provincial health commission … I’d say you were talking out your ass. In fact, your rant about China sounds fucking racist to me.

  6. rcs619 says

    @5:
    My issues are with their government, which is a shitty, oppressive, authoritarian state. Their response isn’t actually that surprising though. The only thing the chinese communist party is obsessed with more than consolidating its power is its public perception. This doesn’t play well with the image they’ve been trying to get the rest of the world to buy into (that they aren’t an oppressive authoritarian state), so they’re going to throw him under the bus.

    Chinese history and culture are really fascinating. Don’t give me that racism shit, lol. Systems of government are not races.

  7. says

    I can tell you that the CCR5 deletion is known, in fact, to make the immune system less competent against some viruses, including influenza. That’s not an unknown. So this was grossly unethical, in every way.

  8. D956 says

    The new era of gene editing really is meaningless when done on yourself. It’s got to be done on embryos, on someone else.

    CRISPR works on somatic cells, offering hope of treatment and enhancement of adults as well. So why do you say this?

  9. petesh says

    @6: This was NOT a government enterprise. And yet you leap to an attack on the Chinese government. Don’t give me that innocent shit.

  10. chris61 says

    @1 rcs619

    Like, I’m all for the eventual genetic improvement of the species.

    I’m not. I envision it turning out pretty much like we’ve tried to do with selective breeding of dogs.

  11. brucej says

    Barry Marshall only performed his ‘experiment’ (more appropriately called a ‘demonstration’ ) AFTER all the (pretty convincing) evidence for his case had been dismissed out of hand, and he literally did not have any other model to use (H. pylori only infects primates, and no one was going to fund $$$ research on primates for what was considered such an outlandish hypothesis; after all EVERYONE (well everyone whose opinion mattered to the medical community) KNEW that ulcers were a lifestyle disease cause by stress.).

    He didn’t ‘randomly lick slime’ off the lab bench.

  12. chrislawson says

    Yep, as brucej says, Barry Marshall only infected himself because it was the only way to get the last bit of evidence that H. pylori followed Koch’s postulates — his gastroenterological colleagues were refusing to accept his hypothesis or proceed with further research. He struggled even to get his papers published (several were rejected outright, and his Nobel-winning paper was published in The Medical Journal of Australia, which is not a bad journal, but it certainly isn’t where you’d expect a paper of this impact to be published.)

    This is not all that different from Stanley Prusiner’s struggle to get the prion hypothesis accepted — his critics kept insisting that he prove all of Koch’s postulates knowing full well that this was impossible in any practical time frame due to its long incubation period, plus the fact that it would never be given ethical approval to deliberately infect people with potential brain-destroying agents, meanwhile people were catching spongiform encephalopathies because nobody was taking precautions against what was considered a ridiculous hypothesis.

  13. chrislawson says

    D956@8–

    CRISPR works on somatic cells, offering hope of treatment and enhancement of adults as well. So why do you say this?

    Because that’s the promise of CRISPR technology, not the reality. As things currently stand, somatic gene editing with CRISPR causes unintended DNA deletions and rearrangements. We used to think that CRISPR changes were at least highly specific to the intended gene location, but we recently learned that it only appeared that way because previous researchers only checked DNA sequences close to the target site. It turns out that on top of the previously observed unwanted on-target effects, some of these disruptions were “deletions extending over many kilobases”, and even worse “lesions distal to the cut site and crossover events were identified.” That is, CRISPR is nowhere near the surgically precise editing tool we hoped it would be.

    There’s a really good PLoS blog post about this paper and what it means for CRISPR therapy. Ignore the clickbaity title, the content is much better than that. Best quote:

    Like a plane crashing into a cornfield, CRISPR-Cas9 landing in the cells blew away thousands of DNA bases at a stretch, the largest 9,500 long. The damage reverberated from the target, triggering chromosomal chaos, while single-base mutations (SNPs) popped up too, even beyond the cut sites. Often, more than one thing went wrong. The assaults could kill a cell or send it on a pathway to cancer.

    CRISPR currently is only usable for embryos (where you can monitor the developing embryo and discard if developmentally abnormal — with the caveat that many abnormalities will NOT be obvious during prenatal development, e.g. increased cancer risk), or where you can take out some cells such as bone marrow, CRISPR a bunch of separate cell lines, discard any failed cell lines, and only reimplant samples that appear to have taken up the intended benefit (this has its own caveats of course). The idea of giving CRISPR to an adult to treat, say, cystic fibrosis is not feasible currently and may never be feasible, even though CF is genetically speaking as simple as inherited disorders get.

    Obviously we all hope that CRISPR or some variant of it will be used to treat conditions safely and effectively. But that’s not where we are now.

  14. chrislawson says

    imaginggeek@3 and cervantes@7–

    Too true. This experiment used a novel technology with known adverse scattershotting that might not reveal itself until well into adult life. And even if the technology worked exactly as intended, the process was designed to give the child a moderate (not complete) immunity to HIV while seriously reducing immunity to influenza. Even with an HIV-positive father, the child’s risk of contracting HIV is essentially zero, and even if that unlucky event happened, modern HIV treatment means that child could expect a normal quality of life for its full span. So this particular treatment makes absolutely no sense from a risk-management perspective let alone an ethical perspective.

    It appears to me that the researcher’s only goal here was publication priority, not the wellbeing of the child or its parents. And I bet you that the parents were misled about the risks of HIV transmission in their situation.

  15. wzrd1 says

    @10, indeed. Look at how well the various royal families of Europe turned out.
    Or the imperial line in China.

  16. jackal says

    chrislawson @13 & @14
    Totally agreed about the risks of CRISPR. Regarding HIV, I wouldn’t go quite as far as to say a life-long HIV infection isn’t a big deal. People living with HIV and on tend to get frailer faster in old age, and we don’t know how children who have been on antiretrovirals their entire lives are going to do in their later years – I think the oldest of them would still be in their 20s. However, if the father was on treatment and had an undetectable viral load, there would be virtually no chance of transmission. To be extra safe, the mother could be on PrEP. It’s a lot easier to prevent an HIV infection than a flu infection. This is a risky genetic experiment that can only be detrimental to the resulting children.

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