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After Such Knowledge

So now we know more about the CRISPR human baby story. And it’s even worse than it looked. Let me recommend this report from Sharon Begley at Stat, from the International Human Genome Summit in Hong Kong, but it’s not going to make you happy to read it.

It turns out that He Jiankui devoted quite a bit more time to working out the publicity for his gene-editing efforts than he did to assessing their implications. He’s had people filming the process for months and has rolled out YouTube videos explaining his project. A good deal of thought went into that part. But when he presented details of the embryo work itself, the audience found that 31 embryos from eight couples (one set of prospective parents later dropped out) had been injected with CRISPR reagents. 70% of these were found to be DNA-edited. Multiple microinjections were needed to try to ensure that the majority of cells in the embryo were indeed affected, He said, and even so neither of the twin girls appears to be a clean job of it. One of them is mosaic for the desired 32-amino acid CCR5 deletion, and the other, if I’m reading this right, is heterozygous for a five amino acid deletion. Wonderful, a complete hack job. (Update: thanks to Sean Ryder on Twitter, we have a graphic showing the actual situation, at right. None of these are the desired 32-residue deletion, and we know nothing about any of them). No reason not to just plow ahead, naturally. I mean, reasonable outside observers might look at this situation and declare the whole experiment to be fearsomely botched up, but History calls. (See this Twitter thread for more details, and here’s a transcript of the talk).

All this means that, in spite of Dr. He’s hand-waving about protection from HIV, we have absolutely no idea if either of these girls will have any such protection from their CCR5 editing. To the best of my knowledge, neither of these genetic backgrounds has been found in the wild-type human population (and let me tell you, it feels very strange to type that phrase, but that’s where we find ourselves now). The two girls will be monitored until they turn 18 (and one hopes afterwards if they give consent), but the effects? Who knows! That’s for them to find out, thanks to the extraordinary arrogance of He Jiankui. If they turn out OK, that will be due to sheer luck. And what will it mean if something bad happens? Who knows! Both of these poor children are one-offs, and cannot even be compared to each other since they’re so different. He did disclose that another pregnancy is underway, but how this third child’s genome has been messed up, I don’t yet know.

David Liu (of Harvard and Beam Therapeutics) was there to ask pointed questions of He (as did several others), and I absolutely agree with him when he said afterwards that “It’s even more appalling and abhorrent now“. Alta Charo of Wisconsin called the whole effort “misguided, premature, unnecessary and largely useless” and that’s right on target, too. I would add “criminal” to that list myself, because it does appear that the consent forms that the parents signed told them that this was an HIV vaccine research project. It appears that Dr. He was the only person to explain the experiment and the consent form to the patients, and God only knows what he told them or what they understood of the work itself. By American legal standards, he has (I’d say) exhibited depraved indifference to human life, and in a better world he’d stand trial for it.

It’s hard to see how this could have been done much worse. It’s obvious that human embryonic gene editing is not ready for use yet, and this is not the work of some brave pioneer because we already knew that. Going ahead with this experiment was reckless, dangerous, counterproductive, and arrogant beyond belief. The title of this post is from Eliot’s “Gerontion”: After such knowledge, what forgiveness? And I do not have it in me to forgive He Jiankui.

109 comments on “After Such Knowledge”

  1. Name says:

    But he probably worked really hard shouldn’t that be enough??

    1. loupgarous says:

      @Name – Depends on how much needless mortality and morbidity follows the participation trophy earned by the slap-dash incompetence of He Jiankui and people like him. In a country where you can “disappear” for saying the wrong thing, it’s ominous that this guy isn’t in trouble with his government (although his own university has disavowed his research, perhaps because the other shoe is already falling).

      Meanwhile, Dr. He’s results bear out the down-side of CRISPR – it’s not yet as accurate in complex living beings such as humans as it is in vitro or in microbes. Not only haven’t targeted results entirely been achieved, but off-target modifications to DNA in some CRISPR research results is also something real to worry about.

      Engineering human fetuses brought to term with CRISPR wouldn’t (I hope) have passed institutional review here – certainly without much more work to show it’s a chisel that won’t turn in the sculptor’s hand.

  2. JB says:

    I’m still of the opinion he picked CCR5 because it’s been well studied in ex vivo human cells and that the HIV resistance benefit is a post-hoc justification (because it doesn’t really make sense, as several sources have pointed out.) So he’s basically doing a validation experiment in humans that you would commonly see in lab animals. Infer what you will from that regarding his underlying view of the patients.

    1. nonchemist says:

      That seems to be the case to me as well. He wanted nothing to do with the safety of these children, nor the stigma against HIV sufferers, nor the development of CRISPR as a tool against human disease.

      What he wanted was the low-hanging fruit, and that he has obtained. May he choke on it.

    2. former Merckoid says:

      Hi JB-

      I’m not a cell biologist, but what is the normal function for CCR5? I mean it didn’t evolve to assist in the entry of HIV, right? It’s more like HIV usurped this receptor.

      Thanks-

      Jim

      1. loupgarous says:

        From “CCR5”, wikipedia.org

        “Recent studies suggest that CCR5 is expressed in a subset of cancer cells with characteristics of cancer stem cells which are known to drive therapy resistance and CCR5 inhibitors enhanced cell killing of current chemotherapy. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear. Regions of this protein are also crucial for chemokine ligand binding, functional response of the receptor, and HIV co-receptor activity.”

      2. loupgarous says:

        CCR5 is part of the beta chemokine receptor family of integral membrane proteins. Published work suggests it may mediate inflammatory response, thought there’s no wide consensus on just how.

        There has been some debate on just how the mutation CCR5-Δ32 which has been associated with resistance to HIV, smallpox and plague was favored. Studies of the populations involved with medieval outbreaks of plague and smallpox suggest that since smallpox attacks younger people than plague does, those children protected by CCR5-Δ32 survived to reproduce during and after these outbreaks to an extent which accounts for the ten percent of northern Europeans who have the mutation in their DNA.

        One of the worrying things about He Jiankui’s work is that there’s no CCR5-Δ32 mutant population in China. For all we know, the mutation may have arisen in China but proven to be reproductively lethal – something happened to those possessing it which kept them from passing it on to future generations.

      3. Wes Kroeze says:

        It’s a chemikine receptor

    3. eub says:

      That seems plausible. I hope a grand jury, or the local equivalent, subpoenas the email trail in pursuit of criminal negligence, because he seems like the type to be arrogantly revealing in email. (Local equivalent may be a party official makes a call to their guy at Apple, which has even less transparency to the public, oh well.)

  3. RiceAlum says:

    It will also be interesting to see how Michael Deem’s involvement is treated here in the US. Based on limited statements, it would appear that his role in this fiasco was non-trivial and–at the very least–he was present in China to consult with (convince?) the families of the GMO babies. It remains to be seen whether this was a case of poor judgment and naiveté, or if Deem advertently outsourced illegal research to a jurisdiction where he would be free from prosecution. It appears that Rice University is carrying out their own investigation, but it would also seem appropriate for current and past federal funding agencies to do a bit of forensic accounting to determine if this work was ever supported using federal funds.

    1. loupgarous says:

      “Rice University said Monday that it had opened a “full investigation” into the involvement of one of its faculty members in a study that purportedly resulted in the creation of the world’s first babies born with edited DNA.

      Michael Deem, a bioengineering professor at Rice, told the Associated Press in a story published Sunday that he helped work on the research in China.”

      So Rice is apparently on the case (as well they should, under the provisions of Title 45, Code of Federal Regulations, Part 46, subparts A and B).

      Not looking into the matter would probably endanger Federal funding for Rice’s research, if nothing else.

  4. S says:

    As @BWJones said on twitter, ‘I’m disturbed that the #GeneEditSummit has not taken a stronger position on this.’ Do leaders in the field secretly think that the only way to get crispr therapies into humans eventually, was to wait until someone unethical did a human ‘trial’?

  5. Mad_Chemist says:

    This is very disturbing. I guess we should be grateful he didn’t expose the children to HIV to prove they were immune.

    1. Appalled says:

      Not yet, anyway. Who knows what he planned for phase 2.

      1. Andrey Yanyuk says:

        His phase 2 plan is on his slides. There’s no planned HIV exposure.

        1. unconvinced says:

          He hasn’t exactly been forthcoming with information up until now, so I will take everything he says about the next phases with a big grain of salt.

    2. loupgarous says:

      Especially since suppression of CCR5 activity was only mosaic in one of the twin girls, and heterozygous in the other.

      Depending on whether or not the mutation is expressed in immune response-related cells, it might or might not protect against HIV (or smallpox, or plague). As Derek said, “a complete hash job”.

      The reaction against this specific work isn’t a case of wanting to suppress work for political reasons – say, a non-scientific reluctance to alter the human genome in this way.

      The way He Jiankui went about his work shows a dangerous lack of scientific rigor. He used those girls and their families as test animals and didn’t even do what we’d accept as good science in the process – likely because opening his research up to institutional review to refine his procedures to develop useful information beforehand would have gotten it shot down fast.

  6. Sok Puppette says:

    Hey, can you not call them “these poor children” quite yet? They’re going to have to grow up in a certain climate of discourse. Pathologizing them before it’s known if they’re harmed is just that much more likely to make people treat them like freaks, and just that much more likely to make them feel like freaks themselves.

    1. RM says:

      They *have* been harmed. They’ve been made to be the subjects of an ill-conceived, misguided, poorly executed and wholly unnecessary experiment.

      Whether or not they suffer any long-term effects is beside the point. If, when you’re under, a surgeon suddenly decides to perform an unnecessary experimental procedure on you, you can still successfully sue them for malpractice, even if you don’t suffer any adverse effects. The doctor doesn’t get to come back with “What are you complaining about? The experimental procedure went fine! You’re not suffering any ill effects.” as a defense. Performing the unnecessary, against-consent procedure was per se harm to you. The fact that you lucked out and didn’t receive any complications from it only mitigates – it does not absolve harm.

      1. Sok Puppette says:

        You’re completely missing the point.

        It’s not a question of absolving *He*. He’s guilty.

        It’s a question of putting these kids in the position of being treated as damaged goods from birth.

        It’s always fun to jump on a bandwagon to punish somebody, but how about not doing any further harm in the process?

        1. James says:

          But that’s missing the point. You can’t truly condemn something if you refuse to acknowledge the harm it’s caused. I get what you mean, and hopefully they can be given some anonymity whatever comes of this, but to pretend they haven’t been harmed takes away from getting across just how big of an atrocity this is. It’d be like saying what went on in the 1940s was bad things that happened without acknowledging the genocide factor

          1. Sok Puppette says:

            Yeah, no, sorry.

            You don’t use a phrase like “these poor children” unless you intend to convey that somebody is *suffering*. Which is not such a hot idea when that very attitude may end up being what causes the suffering.

            Call it harm if you want. Many people do talk about risk of harm as a form of harm. It’s not required, though. You can still say it’s unacceptable to create a *risk* of harm.

            But it’s really irrelevant; fine, call it harm if it makes you happy. That still doesn’t justify the damaged goods language.

        2. MM says:

          I’m assuming these kids will grow up to know they’ve been edited, and consequently will eventually come to realize that they may get cancer (for example, and among other possibilities). This mental stress in and of itself is extremely harmful, like someone with a 50:50 changes of getting Huntington’s disease waiting for it’s onset (or not).

          1. eub says:

            Well, I think the point is that He harmed the children, we don’t need to harm them any more, by laying on somewhat-stigmatizing characterizations of the harm.

            I mean I can certainly feel where “these poor children” comes from, it’s a pretty short step between that and purely describing the facts. But we could call them “wronged children” instead of “poor children”, say.

    2. loupgarous says:

      Their personal genomes have been altered in ways that don’t correspond to the way ethical human experimentaton is done. That’s why.

      I strongly suspect that the human experimentation provisions of the Helsinki Declaration were violated in this study, not just by the PI, but even by an American colleague of his. Scientists who know better ganged up on the parents of these children to use them as test subjects for research which wasn’t just unethical, but incompetently done.

      Not talking about how those two girls were abused at a previously inconceivable level – in their DNA – isn’t going to protect them or make their lot easier in any meaningful way. Expressing compassion for them, within reasonable limits, is entirely appropriate.

  7. Dr Sarcasm says:

    It’s a good job he doesn’t work in industry, otherwise he wouldn’t be able to publish any of this.

  8. Fuh Dge says:

    To add the nth problem to the list, did He Jiankui even validate that the father’s HIV has CCR5 tropism? I couldn’t find data backing that in the slides. I know CXCR4 tropism is much rarer in HIV, but the work would be especially perverse if the father was infected with HIV that didn’t even use CCR5 for entry.

  9. anon says:

    He should be taken out of the lab and never be allowed in again.

  10. Henry Wolfe says:

    This was entirely predictable, especially that it would occur in China. Too often we scientists fail to ask “should we” after getting a new tool

    1. JB says:

      Are we supposed to have a shirtless picture of Jeff Goldblum to go with that last sentence?

    2. zero says:

      I seem to recall rather a lot of “should we” debate on this topic, starting around the time we realized it would be possible one day. A wide spectrum of opinions exist, but virtually all of them rest on reasonable evidence of safety as a minimum and fundamental requirement for human trials.

      The problem here is that one particular ego decided to flip the table instead of win the debate.

      Imputing He’s opinions upon the scientific community is not justified, any more than Turing Pharma’s egregious behavior represents the industry or fanatical religious terrorists represent average believers.

  11. KN says:

    Predictably, it was too big a temptation for someone to take chances to become The First One, when all it takes basically is to ignore ethics: all the tools are already here.

  12. Bertz says:

    Derek – Are you saying that mosaic Delta32 mutants didn’t exist in human populations (which is obvious), or that the Delta32 mutant itself doesn’t exist? I believe the Delta32 variant is relatively common in European populations.

    1. T.Bann says:

      I believe what was meant was that one child is a mosaic for the “desired” 32 amino acid CCR5 deletion. The European mutation was not involved except as an attempt to justify the experiment.

    2. mike says:

      “mosaic” as in some of the cells have the mutation and some don’t. Although the mosaicism was at the blastocyte level, and Dr. He claims it has not been detected in the child. The second child appears to have a completely different mutation, “a .. deletion, which was expected to maybe destabilize local protein confirmation around adjacent HIV1 binding site”. And Dr. He is not apparently claiming the European delta32 mutation, but ” …a frameshift lockout, which should shorten the CCR5 protein similar to the natural protective variation.”

      As for those who immediately jumped to predicting cancer as the inevitable result of gene editing, please note that induction of CCR5 is also implicated in metastasis of cancers and a CCR5 knockout might be expected to be favorable against cancer.

      1. Andrey Yanyuk says:

        I believe the Delta32 variant is the frameshift lockout

  13. EDT says:

    Interesting article this morning in the front page of the “The Mercury News” alluding that He had very little understanding of medical ethics. Why was this?

    1. Passerby says:

      Probably because the regulatory environment and ethics committees in China are non-existent?

  14. Isidore says:

    Between the desire
    And the spasm
    Between the potency
    And the existence
    Between the essence
    And the descent
    Falls the Shadow

    1. KS says:

      This is the way the world ends
      This is the way the world ends
      This is the way the world ends
      Not with a bang, but a whimper

  15. MTK says:

    That Stat story got my blood roiling.

    The whole manner in which this has been conducted is horrible. The PR campaign, the false mea culpa for the “leak” prior to peer review, the lack of transparency, poor experimental design, lack of medical urgency, dubious at best informed consent, etc., etc. This thing stinks all around and it stinks from the head down. He should be stripped of any and all credentials he may have and should be universally shunned by the scientific community and that includes the rejection of his paper by any and all publications. One cannot legitimize this type of unethical work.

  16. dave w says:

    What strikes me as a weird point of irony about all this is that, for once, there was at least the attention to technical credibility whose lack is often complained of: there may well be strong reasons to doubt the ethics and utility of what was actually accomplished, but it seems nobody is making accusations of “fake results”, with photoshopped gel bands etc – the researchers apparently did get the results they reported…!

    1. MrRogers says:

      Of course they did. CRISPR has worked to the extent that they report in every species where it’s been tried. That doesn’t make this right, or even well thought out.

    2. loupgarous says:

      There’s no reason to suspect that when Gregor Mengele did what he did to concentration camp inmates, he was less than honest in documenting every atrocity to his mentor Professor Otmar von Verschuer of the Kaiser Wilhelm Institute of Anthropology.

      It’s not often that a research scandal involves the next step down the ladder from fraudulent reporting, to research on humans in the dark, with no institutional review, and with no apparent object other than to show the utility of a way to edit DNA of a human fetus.

      While the specific act was to edit a protein in a way that would confer resistance to at least one deadly virus (possibly two deadly viruses and the plague bacillus ), it wasn’t a therapeutic intervention, just a tour de force. So yes, this is something new for this blog. And scary.

  17. JB says:

    Let’s stop pretending like the Chinese authorities really care. If CRISPR can be weaponized to make more intelligent, stronger, or you name it humans that could be soldiers for the PLA, you can bet that behind the curtain they don’t really care if they have to crack a few eggs to make an omlet. The Chinese want to be the first to do it, and they do not share the same midset when it comes to ethics as the west does. You may think that’s all fabricated nonsense, but we are talking about a country that forced two people to marry and have a kid named Yao Ming who would have superior traits for basketball, we are talking about a country that currently just forcing non-muslim citizens into the homes of Muslims to report on their behavior, and we are talking about a country that is implementing a dystopian Orwelllian like social credit system to regulate their people. They don’t care at all about the ethical ramifications about CRISPRing babies.

    1. Scott says:

      Incorrect, sir!

      “HONG KONG (AP) — China’s government ordered a halt Thursday to work by a medical team that claimed to have helped make the world’s first gene-edited babies, as a group of leading scientists declared that it’s still too soon to try to make permanent changes to DNA that can be inherited by future generations.

      Chinese Vice Minister of Science and Technology Xu Nanping told state broadcaster CCTV that his ministry is strongly opposed to the efforts that reportedly produced twin girls born earlier this month. Xu called the team’s actions illegal and unacceptable and said an investigation had been ordered, but made no mention of specific actions taken.”

      1. Anon says:

        The ‘specific actions taken’ may now be a bit clearer. Jiankui has vanished.

        https://thehill.com/policy/technology/419462-chinese-scientist-who-claimed-gene-editing-success-now-missing-report

        He is rumored to be under house arrest.

    2. X says:

      Let’s stop pretending that it’s just the Chinese government lol.
      It’s very bold to claim that any region in the world has superior ethical or moral standards, and particularly bold to claim that it’s “the West” that has. Did you even study history outside of whatever propaganda you were fed?

  18. Christophe Verlinde says:

    He Jiankui transgressed Chinese law and the standards of moral behavior. He clearly belongs in jail.

  19. anon says:

    So, if the girls are able to reproduce, he basically introduced a new CCR5 mutation into the general population of which the effects are unknown.

    1. John Wayne says:

      Zombies.

    2. Anon says:

      the new allele will be recessive though.

  20. Leon says:

    After such knowledge, what forgiveness? Think now
    History has many cunning passages, contrived corridors
    And issues, deceives with whispering ambitions,
    Guides us by vanities. Think now
    She gives when our attention is distracted
    And what she gives, gives with such supple confusions
    That the giving famishes the craving. Gives too late
    What’s not believed in, or is still believed,
    In memory only, reconsidered passion. Gives too soon
    Into weak hands, what’s thought can be dispensed with
    Till the refusal propagates a fear.

  21. Chairman Mao says:

    Well I was born in Test tube
    There’s not a lot of room in a Test tube
    Probably die in a Test Tube
    Oh, those Genetic Anomalies

    All my friends are from Test tubes
    My dad He made us from US-based reagents (enabler hypocrites)
    All my genes have been CRISPRed
    Which makes Darwin spin in his grave

    Sing It to the John Mellencamp song ” I was Born in a Small Town”

  22. Scott says:

    Wow, that’s even worse than I thought!

    Whiskey Tango Foxtrot?!?

  23. Abbvie and Costello says:

    I really hope that the second person to successfully CRISPR a human embryo is named Who.

      1. Anonymous says:

        Hu’s on first.

        (Link in name.)

  24. Handles says:

    I laughed at the picture of the conference in the Stat article. The University of Hong Kong, hosting a summit on human genome editing, draws the mirror-image left handed DNA helix. That would indeed be a great feat of genome editing!

  25. For everyone dumping on the Chinese government and culture, please let us know what law prevents this being done with private funding in the U.S.

    1. Derek Lowe says:

      A lot of people don’t realize that there’s no law against germ-line editing in the US. You can’t use NIH money to do it, as you allude to, but you would be breaking no laws (as long as you handled the informed consent with care, which may well not have been the case here).

      1. Stuart Newman says:

        Just as British and U.S. eugenics theory and practice of the late 19th and early 20th centuries provided the template for the Nazi final solution, so have the British and U.S. laid the groundwork and provided the justifications for this latest assault on humanity, with the tip of the iceberg emerging in China (though U.K. approval of 3-person reproduction advanced the agenda). Developmental genetics became linked to big money in 1980 with the Bayh-Dole Act and the Chakrabarty Supreme Court decision. With prenatal diagnosis becoming taboo as a justification for funding at Reagan’s NIH, the tacit, distant goal shifted to embryo improvement. The drumbeat got louder with every improvement in DNA manipulation. There was never an incentive to take promises of eventual molecular eugenics off the table.

    2. Not the Null Hypothesis says:

      I’m pretty sure an Attorney General would find a law to prosecute.

  26. Fred the Fourth says:

    So, how DOES one go about getting informed consent from a zygote?
    (Yes, I know about parental authority. Still.)

  27. Not the Null Hypothesis says:

    This makes all my screw UPS in grad school look a lot better. Joking aside will the modern day Josef Mengele be charged for this BS, or is it still the wild west in China?

    1. Isodore says:

      Under which law(s) would you charge him on the US or the EU countries?

      1. Derek Lowe says:

        Exactly. Unless there’s some funny business with informed consent, etc., He may well have broken no Chinese laws. Actually, if he’d done it here in the US with private money (and again assuming real informed consent and so on) he wouldn’t have broken any US laws either, I believe. We have no law against germline manipulation.

        1. Not the Null Hypothesis says:

          No, but there are laws around tampering with pharmaceuticals used and experimental drugs require an IND before patient exposure. You work in the Pharma industry, you know that. Were proteins engineered and produced under cGMP regulations, because we have a Code of Federal Regulations for that… Please get real, there was nothing legal about what this guy did. In the US he would be prosecuted.

          1. Isidore says:

            Arguably this is not a drug but a surgical procedure to excise a gene permanently. I have no idea how novel surgical procedures are regulated.

          2. Not the Null Hypothesis says:

            Seems you just can’t admit that you are wrong, so you stretch to something that’s not even relevant. If you inject an anesthetic into a patient and do surgery, and that anesthetic isn’t an approved drug do you think the doctors get to use the argument that it was surgery? No.

      2. Ian Malone says:

        In the UK, the Human Fertilisation and Embryology Act 2008, and possibly the human tissue act 2004. Only “permitted embryos” should be allowed to develop past an early stage, DNA alteration is not allowed in permitted embryos, with one exception made for “an embryo can be a permitted embryo, even though the egg or embryo has had applied to it in prescribed circumstances a prescribed process designed to prevent the transmission of serious mitochondrial disease.” I mention the Human Tissue act because my vague knowledge of it is better than my even vaguer knowledge of the HFEA, and it requires a recognised research ethics committee to approve the research, https://www.hfea.gov.uk/about-us/applying-for-a-research-licence/ suggests similar is needed for work under that act.

        Not a lawyer, but looks like this would have been illegal in the UK. The law was changed very specifically to allow the mitochondrial transplantation work, but I don’t see any loopholes for nuclear genetic editing.

        (1)This section has effect for the interpretation of section 3(2).

        (2)A permitted egg is one—

        (a)which has been produced by or extracted from the ovaries of a woman, and

        (b)whose nuclear or mitochondrial DNA has not been altered.

        (3)Permitted sperm are sperm—

        (a)which have been produced by or extracted from the testes of a man, and

        (b)whose nuclear or mitochondrial DNA has not been altered.

        (4)An embryo is a permitted embryo if—

        (a)it has been created by the fertilisation of a permitted egg by permitted sperm,

        (b)no nuclear or mitochondrial DNA of any cell of the embryo has been altered, and

        (c)no cell has been added to it other than by division of the embryo’s own cells.

        (5)Regulations may provide that—

        (a)an egg can be a permitted egg, or

        (b)an embryo can be a permitted embryo,

        even though the egg or embryo has had applied to it in prescribed circumstances a prescribed process designed to prevent the transmission of serious mitochondrial disease.

        (6)In this section—

        (a)“woman” and “man” include respectively a girl and a boy (from birth), and

        (b)“prescribed” means prescribed by regulations.”

        1. Michael Striker says:

          Being myself a somewhat callous individual, I must ask “How will mitochondrial transplants affect genetic matrilineal descent tracking? Does it matter?” (I recognize the humanity of doing such transplants. I find the irony of messing with our history-tracking tools to save some in our present humorous.)

      3. loupgarous says:

        here in the States (for any American co-investigators) the governing law would be Title 45, Code of Federal Regulations, Part 46—Protection of Human Subjects, Subpart A—”Basic HHS Policy for Protection of Human Research Subjects” and
        Subpart B—”Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research”.

        specifically, check out 45 CFR 46 Subpart B,

        Section 46.204 Research involving pregnant women or fetuses.
        Pregnant women or fetuses may be involved in research if all of the following conditions are met:
        (a) Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
        (b) The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
        (c) Any risk is the least possible for achieving the objectives of the research;”

        I see potential violations of every term in section 46.204 (above)

  28. An Old Chemist says:

    Now, let us hope that a genius like David Liu will make another CRISPER breakthrough which will help to undo the damage done to these babies of Dr. HE.

    1. Lars says:

      Let’s not make the cure any worse than the disease now.

  29. John Milton says:

    Do humans have intrinsic moral value? Are we not all sophisticated animals?

    1. Derek Lowe says:

      This, as you might well imagine, is a topic that has been taken up over the last two or three thousand years of philosophy, and even more as we have learned more about biology. It defies easy summary, but I think that the best answer to your first question is “yes”.

  30. Jim Hartley says:

    I wonder if the bad odor around CRISPR created by Dr. He’s experiment will cause the Nobel committee to delay?

  31. An Old Chemist says:

    The hollywood movie ‘Jurassic Park’ helped Kerry Mullis get a Nobel prize for PCR technology. And so, Dr. HE’s crazy experiments may indeed help CRISPR researchers get their Nobel. We still have about 10 months to go for the 2019 Nobel prizes and by then a lot of new info will have been obtained about Dr. HE”s phase-3 clinical twin baby trials.

  32. EE says:

    China is the only major country without any solid religious/moral system (confucianism can barely count). In other words, despite millions of decent Chinese people, overall we are dealing with a nation of barbarians. More to come.

    1. Derek Lowe says:

      Careful there. I’m not religious myself, but I think that you can have morals/ethics without a religious foundation. On the other hand, there is a sort of culture of expediency, and you can talk about that without making grand statements about religious systems.

      1. Jane Roe says:

        Yeah, it’s crazy to think the Chinese are less moral or ethical or even less religious. After all, what is two modified embryos to a country with a six-figure death toll alone?

        https://en.wikipedia.org/wiki/Abortion_statistics_in_the_United_States

        1. loupgarous says:

          You’re right – governments in general decide things pragmatically, not on the basis of morality. Occasionally morals and practical politics overlap, but there’s also the issue of whose morals ought to control

          The Chinese government’s suppression of some religions (Falun Gong and Islam, say) and co-opting of others (such as Catholicism) is an entirely separate issue from one Chinese researcher’s decision to do sloppy work on human embryos and bring them to term without any consultation or institutional review.

          In this case, the Chinese government apparently didn’t even have the chance to weigh in on the decision until Dr. He held his press conference.

    2. Kevin H says:

      I mean, there obviously aren’t any unethical researchers in those God-fearing Christian countries.

      Except for Andrew Wakefield, Carlo Croce, Ranjit Chandra, Paolo Macchiarini, Elizabeth Holmes….

      Did you want to try again?

      Derek, I’m a little bit disappointed and saddened that you didn’t just delete a racist comment. You have no obligation to give posters like that a platform.

      1. Disappointed says:

        Kevin, I agree with you. Derek’s complicity with such a racist’s comment is truly disappointing!

      2. Derek Lowe says:

        That one was right on the edge, I have to admit.

      3. anonymous says:

        Croce is out at Ohio State.

    3. loupgarous says:

      Germany in the 1930s, however, was well-provided with several religious and ethical systems. Their government elected to persecute and eventually kill millions of Germans and other Europeans for belonging to the wrong religious tradition.

      The Vatican not only didn’t protest this until it was far too late, but actually entered into a treaty with the Nazis to protect its own faithful – destroying any political or moral independence of its German clergy and bishops from the Nazi Party. Concordats like this were signed between the Vatican and several oppressive regimes, such as Duvalier’s Haiti. More recently, the Vatican’s letting Beijing choose bishops in the Chinese branch of Roman Catholicism.

      I’m not just picking on Rome. I’m an Episcopalian who’s disgusted with the Anglican Communion’s tolerance of persecution of people on the basis of gender in several of its national Sees, while letting them interfere in governance of my own church for decades. The Church of England had a slave plantation on Barbados, and branded its human property across their chests to be sure none were able to escape captivity and pass as freedmen.

      Religious systems aren’t necessarily moral ones.

      1. loupgarous says:

        correction: The Reichskonkordat was drafted before the collapse of the Weimar Republic, so the treaty wasn’t initially an agreement between Hitler and the Pope, but Reichspräzident Hindenburg of the Weimar Republic and the Pope.

        Article 16 of the Reichskonkordat obliged bishops to swear “…In the due solicitude for the welfare and the interests of the German Reich, I will endeavor, while performing the spiritual office bestowed upon me, to prevent anything which might threaten to be detrimental to it.”

        The Reichskonkordat was never repudiated after Hitler’s rise to power, and remains in effect today. Technically, Roman Catholic bishops in Germany are still bound by its provisions.

  33. Peter S. Shenkin says:

    On the one hand, I hope that these kids will grow up healthy and happy.

    On the other, that might be the worst possible outcome, in that it would encourage further reckless experimentation of the same sort.

    1. loupgarous says:

      Those kids growing up happy and healthy wouldn’t be a bad thing under any circumstances.

      It’s up to responsible parties in government, academia and medicine to recognize the danger posed by what happened to them, and to society to build a consensus on why it was wrong and how to prevent it from happening again.

    1. Derek Lowe says:

      Yeah, and I wasn’t alone by any means. But this was worse than I expected.

  34. AnonScientist says:

    I feel sick after reading this. An unethical and probably pointless experiment failed. Nonetheless it was continued playing with the lives and health of innocent babies. Why?

  35. An Old Chemist says:

    Derek, you say that you are not religious, but I note that in this post you have written “God only knows…. “. I am a practicing Hindu and I totally sgree with you that God only knows the future of these babies.

  36. eub says:

    Times like this I almost wish we had capital punishment with harvesting of useful organs. Not really. But almost.

    “it does appear that the consent forms that the parents signed told them that this was an HIV vaccine research project”

    This fucking guy. What a waste of kidneys.

  37. anon says:

    Not the expert on the field, but to summarize (please correct, if wrong).
    There are several teams around the world, which are able to use CRISPR technology on animals. Everybody is aiming to do it on human, when it is developed enough. He wanted to be the first one, therefore he used technology evaluated/working on animals straight on humans.
    Same level, as if I would use my small molecule, which works great in MCF-7 cell line, as anticancer agent in human.
    Only “novelty” in this case is, that you do not care for consequences (or is there any technical/scientific achivement behind).
    How many teams around the world are able to repeat the same in animal?

  38. Emjeff says:

    I think the worst part of this (among all of the horrible breaches of ethics which have occurred) is that the end-point this guy chose for the experiment is completely and utterly pointless – who cares about CCR5? In effect what he has done is a Phase 1 study in babies. If he had actually used embryos with an actual genetic defect and corrected said defect, this action would be 0.00001% less repugnant. Instead, he used a biomarker of CRISPR activity in a vulnerable population (something he could have done, BTW, in an animal embryo), and has essentially pointless results.

  39. F. Li says:

    He’s CRISPR experiment was flawed , unethical and he and his collaborators deserve legal, financial, and moral punishment. With that said, I sense quite a few the well-educated scientists here “lazily” linking his behavior to China by large (culture, religion, politics etc..).
    At best this is lazy thinking, at bottom of heart this is subtle racism.
    Just look around this country, where God-loving, democracy etc have empowered a lier and moron to become a president. Don’t get me started on so many non-translatable, non-reproducible Science, Nature or Cell papers! Should not we blame the culture/system/religion here?

  40. Snark: Humanity’s “Sixth Day”* approaches. Now what?

    Seriously: The U.N.’s IBC (article linked in name, I think) stated “Interventions on the human genome should be admitted only for preventive, diagnostic or therapeutic reasons and without enacting modifications for descendants.”, back in 2015. He’s work fits the first portion (for preventative reasons), but now necessitates an answer for the second portion (potential descendents).

    While Dr. J. He deserves what the world decides, what will be the fate of the twins?

    * – property of Phoenix Pictures & Columbia Pictures

    1. loupgarous says:

      Thanks for sharing that with us, because it’s another thing someone at the UN decided to decree without consulting the rest of us who pay their bills.

      “Bioethicists” at times don’t seem all that ethical. The UN International Bioethics Committee’s pronouncement that “Interventions on the human genome should be admitted only for preventive, diagnostic or therapeutic reasons and without enacting modifications for descendants” is (in my humble opinion) a prime example of a questionable policy.

      Why should an in vivo genetic repair be forbidden if it confers the repair on future generations? Dr. He’s offense wasn’t doing that, but doing it without any outside review or prior discussion.

      There are plenty of heritable disorders which we ought to discuss editing out of the human genome. Sickle cell anemia, a mutation which had survival value against malaria, is an example of a genetic error we should discuss editing out of our genome. Before genetic engineering and CRISPR, the only corrective for sickle cell anemia was to discourage carriers of the gene from having children, both a drastic remedy and a politically untenable one.

      We may have better alternatives to the harsh, dystopic world of John Brunner’s 1968 science-fiction novel Stand on Zanzibar, a prodigy of solid futurism, seamy sexual passages and shrill social preaching. The novel, set in 2010, has the United States of America and other highly industrialized nations forbidding birth of children with genetic defects by law – the legally prescribed actions being contraception, sterilization and abortion. (The Roe v. Wade precedent which now guarantees women the right to abortion might someday be seen as by conservatives and libertarians as a defense against such laws, but it had yet to be handed down when Brunner wrote Stand on Zanzibar)

      I am not saying we ought to blindly rush to remove genetic defects from the human genome. Derek, in another blog this week, you bring up the “Chesterton’s Fence” paradox

      In the matter of reforming things, as distinct from deforming them, there is one plain and simple principle; a principle which will probably be called a paradox. There exists in such a case a certain institution or law; let us say, for the sake of simplicity, a fence or gate erected across a road. The more modern type of reformer goes gaily up to it and says, ‘I don’t see the use of this; let us clear it away.’ To which the more intelligent type of reformer will do well to answer: ‘If you don’t see the use of it, I certainly won’t let you clear it away. Go away and think. Then, when you can come back and tell me that you do see the use of it, I may allow you to destroy it.'[

      , in which we’re counselled against removing seemingly pointless inconveniences until we’ve considered why they exist in the first place.

      I don’t actually mind the idea of permanently deletling mutations which cause – or in the case of the wild type CCR5 protein, allow – diseases from the human genome, but it ought to be done after learning why the mutations were selected for to begin with, in laboratories where Chesterton’s Fence is engraved in the walls of every long hallway.

      1. eub says:

        Sickle cell anemia, a mutation which had survival value against malaria, is an example of a genetic error we should discuss editing out of our genome.

        Had, or has? Heterozygous sickle cell trait is a live benefit today, in people living under malaria, yeah?

        The disease burden of malaria is still damn high. I would not be surprised if calculations show sickle cell is net beneficial (I haven’t seen this done), though no comfort to the people who end up homozygous.

        I humbly suggest we eradicate malaria first, or at least get countermeasures out there to slash the disease burden 95%. I would also take proposals for eradication of Anopheles ssp., though that’s not a simple game to play.

        1. Scott says:

          Agreed. malaria is still a major problem everywhere in the world.

          Let’s nuke malaria out of existence long before we consider editing the sickle-cell traits out of the gene pool!

          1. loupgarous says:

            You’re right, and I thoughtlessly ignored Chesterton’s Fence/the precautionary principle after going on and on about it earlier.

            But I am curious whether sickle cell trait actually has a net protective effect today. Strains like falciparum may be so virulent that sickle cell trait may no longer exert the same protective effect that led to conservation of that gene in Africa and the Mediterranean coast.

            Studies seem to be called for, but with an eye out for confounding variables that might create the false impression that sickle cell trait either is or is not protective with today’s strains of malaria.

          2. loupgarous says:

            For African-Americans, deletion of sickle cell trait is much less problematic than doing that in African, the Mediterranean coast, and South Asia.

            A New York Times article, “Fatal Malaria in the U.S. More Common Than Previously Known” says that the 22,029 patients hospitalized for malaria between 2000-2014 in the United States (I calculate that as 1,573.5 a year) were typically immigrants, missionaries or other people who recently returned from areas where Plasmodium falciparum is endemic.

            The risk/benefit ratio probably favors deletion of the sickle cell trait among carriers who are US residents and unlikely to travel where malaria is endemic.

  41. Disbelieve says:

    How low can we go? This “work” is now being praised by yahoo finance.

    https://finance.yahoo.com/news/genetic-editing-software-crispr-weeks-champ-162452320.html

    I guess that’s what He was shooting for, truly sickening…

  42. anononon says:

    The first thought I had when I read this was something like “isn’t there a lot of personal, existential risk if this goes poorly and you embarrass the Chinese government?”.

    And low and behold, we are now seeing the first rumours that He has gone missing. I can hardly applaud government sponsored “disappearances”, but I suppose you reap what you sow.

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