Genetically Modified Humans Born (Allegedly)

post by ryan_b · 2018-11-28T16:14:05.477Z · score: 30 (9 votes) · LW · GW · 12 comments

I realize normally we don't talk about the news or hot-button issues, but this is of sufficiently high importance I am posting anyway.

There is a link from Nature News on Monday here. There is a link from MIT Technology Review discussing the documents uploaded by the team behind the effort here.

Summarizing the report I heard on the radio this morning:

I don't think DNA testing of the twins has taken place yet. If anyone has a line on good, nuanced sources, I'd be interested in hearing about it.

12 comments

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comment by Said Achmiz (SaidAchmiz) · 2018-11-28T16:31:29.619Z · score: 25 (10 votes) · LW · GW

Transcript of He Jiankui’s comments at the Second International Summit on Human Genome Editing (plus Q&A).

comment by ryan_b · 2018-11-28T17:47:10.049Z · score: 4 (3 votes) · LW · GW

That's an interesting transcript. It managed to decrease my confidence in the ethical frameworks we have set up around medicine; most of the questions were about forms, training for forms, number of institutions to whom the forms were submitted, etc. Only a few of those questions went right to the heart of the ethical problems. Those questions were:

  • How do you see your obligation to these children?
  • Are you sure the parents understood what they were doing?
  • Would you do this to your own child?

There doesn't seem to be any articulation of the risks during the session, or plans for dealing with them.

comment by Thrasymachus · 2018-12-02T05:10:44.786Z · score: 14 (5 votes) · LW · GW

Once again I plead that when you see that an expert community looks like they don't know what their doing, it is usually more accurate to 'reduce confidence' in your understanding rather than their competence. The questions were patently not 'about forms', and covered pretty well the things I would have in mind (I'm a doctor, and I have fairly extensive knowledge of medical ethics).

To explain:

  • Although 'institutional oversight' in medicine is often derided (IRB creep, regulatory burden, and so on and so forth), one of its main purposes is to act as a check on researchers (whatever their intent) causing harm to their patients, and the idea it is good to have other people besides the researcher (who might be biased) and the patient (who might be less well informed) be the only ones making these decisions. That typical oversight was bypassed here is telling, but perhaps unsurprising as no one would green-light violating a moratorium to subject healthy embryos to poorly tested medical procedures for at best marginal clinical benefit.
  • A lot of questions targeted how informed the consent was, because this was often relied upon in the presentation (e.g. "Well, we didn't get the right mutation, but it was pretty close, and the parents were happy for us to go ahead, so we did").
  • The 'read and understand' question (I'm using the transcript, so maybe there were dumber questions which were edited out) wasn't a question about whether the patients were literate, but whether they had adequate understanding of (e.g.) the technical caveats which they were giving consent to proceed with (e.g. one mutation was a 15 del rather than a 32 del, which rather than the natural mutation which induces a frame shift and the non-functional protein gives a novel protein with a five aa removal, which may still generate an HIV susceptible protein and some remote chance of other biological effects).
  • The 'training' question is because establishing whether consent is 'informed', or providing the necessary information to make it so, isn't always straightforward (have you ever had a conversation where you thought someone understood you, but later you found out they didn't?) I did a fair amount of this in medschool, and I don't think many people think this should be an amateur sport.
  • (As hopefully goes without saying, having two rounds of consent where in each the consent taker is a researcher with a vested interest in the work going ahead has obvious problems, and hence why we're so keen on third party oversight).
  • I also see in the transcript fairly extensive discussion about risks (off-target worries would have been tacit knowledge to the audience, so some of this was pre-empted in the presentation then later picked at), and plans for followup etc.
comment by ryan_b · 2018-12-05T16:13:46.230Z · score: 5 (3 votes) · LW · GW

Nothing you are saying comes as a surprise, but my confidence in the process remains reduced. The problem here is that having a procedure for establishing whether a patient is informed, all of the weight rests on the procedure, and virtually none on the practitioner. This is the same for all fields of expertise.

I have read many of these kinds of forms as a patient. What we want them to be for is informing the patient; what they are actually for is defending against the accusation that the patient was not informed.

The audience was very much preoccupied with how the procedure for informing the patient was conducted, and seemed to consider this the biggest red flag. I find the fact that the lead scientist kept referring to a form to be the biggest red flag, because it suggests he didn't engage the ethical issues directly.

Suppose for a moment that he did a much better job informing the patients - proper training, third party verified composition, etc. I don't think this would have any implications at all for how He Jiankui engaged with the question of whether it was right to do this, but I do expect the audience to have been largely mollified. I see this as a problem.

comment by gwern · 2018-11-29T15:42:12.483Z · score: 11 (4 votes) · LW · GW

Watching the Q&A was mindbending, and reminded me why I dislike bioethicists so much. Asking He Jiankui whether the participants were literate enough to read the forms! (You got one question, with so many important things to ask, and that was the point you decided to make?)

comment by CellBioGuy · 2018-11-30T03:02:28.921Z · score: 17 (7 votes) · LW · GW

Coming out of hibernation specifically to comment on this.

There is now reported gene sequencing info. The 'edit' is an unmitigated disaster hack-job - random insertions and deletions caused by desperate DNA-repair machinery, not a clean adjustment to a known allele. Just like what tends to happen a lot of the time when you try to CRISPR mammals that love non-homologous end joining rather than microbes that like to use homologous recombination. It is a LOT easier to just take a chainsaw to a genome and break stuff rather than actually edit cleanly. For lab animals you can just keep trying until you get it right then breed it. But now the two sequenced people (both apparently are MOSAICS of multiple different mutations!) have alleles never before seen that we have no idea what the immunological impacts of are.

Responsible research, this is not. Ghoulish tinkering with human subjects.

https://blogs.sciencemag.org/pipeline/archives/2018/11/28/after-such-knowledge

comment by CellBioGuy · 2018-11-30T03:14:30.920Z · score: 13 (6 votes) · LW · GW

Quotes from people in the field now that more information was divulged:

------

' “It’s even more appalling and abhorrent now,” Liu, cofounder of the genome editing company Beam Therapeutics, told STAT. “His responses displayed a deeply disturbing naivete about the issues involved. I have a deep fear that this could set back the field [of therapeutic genome editing] so badly that patients won’t get the therapies they desperately need.”

Other experts in the audience were equally critical. “Having listened to Dr. He, I can only conclude that this was misguided, premature, unnecessary, and largely useless,” said bioethicist Alta Charo of the University of Wisconsin, a member of the summit organizing committee. '

------

' 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.'

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' We work with worms and zebrafish to generate precise point mutations. The amount of screening required to find a precise edit among the mix of indels and complex rearrangements/insertions makes me shudder at the thought of attempting this so brazenly in patients. '

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'The technology is immature, this was an inappropriate modification, AND HE DID IT INCOMPETENTLY. I have no words. '

comment by ryan_b · 2018-11-30T17:14:21.172Z · score: 5 (3 votes) · LW · GW

I did not know what to expect, but I am not surprised.

I am now interested in how this plays out from an alignment perspective. It seems to me that the ethics of genetic editing have been taken pretty seriously by practitioners, and I'm tempted to make an analogy between the ethics here and safety in AI.

I really hope those kids are okay.

comment by ChristianKl · 2018-11-28T17:41:10.477Z · score: 3 (5 votes) · LW · GW

An interesting part from the Nature article:

“This is a huge blow to the international reputation and the development of Chinese science, especially in the field of biomedical research,” the statement says. “It is extremely unfair to the large majority of diligent and conscientious scientists in China who are pursuing research and innovation while strictly adhering to ethical limits.”

It's a huge blow to the development of Chinese science when their science doesn't let itself get limited by burocracy...

comment by Sapient Coccolithophore · 2018-11-28T20:25:22.995Z · score: 1 (3 votes) · LW · GW

That last word is a typo.

comment by gjm · 2018-11-29T15:53:35.473Z · score: 4 (3 votes) · LW · GW

In fairness, "bureaucracy" is an unusually difficult word to spell correctly (though splitting it as bureau/-cracy, the former being an English word and the latter the suffix in democracy, autocracy, etc., helps) and Christian is not a native anglophone.

comment by Leafcraft · 2018-11-29T08:51:37.015Z · score: 1 (1 votes) · LW · GW

As someone who works in the field, I am very skeptical about these kind of statements from scientist in eastern countries (China in particular), and while events described are certainly within the realm of possibility, I'd rather wait until more evidence is available before taking the new seriously.