[ak217]

The concerns about the LHC were a hell of a lot more hypothetical than about germline editing, and that did change the calculus. We know that current genome editing techniques have off-target effects.

You're arguing from some abstract philosophical perspective, but the practical situation is much simpler. Nobody is drawing categorical conclusions and saying that we should never edit the germline, and at the same time the opinion that we should do germline editing right now is fringe. The tools, while much better than ten years ago, still suck. Outside a few well-characterized alleles in Mendelian diseases, nobody knows what to edit, what side effects edits will have or why. It's likely that in a few years we will know, given that we're quickly improving both the molecular techniques and the genome knowledge bases necessary to understand the consequences of the edits. But until then, it's dangerous and unethical to experiment on babies without their consent or pressing medical need, and scientists are right to freak out about it.

[wahern]

If you believe that germline gene editing is so risky and potentially costly as to be absolutely unwarranted, then you shouldn't support somatic gene therapy as there remains a very real and non-negligible risk of germline integration. Some vectors might be safer than others, but proving the impossibility of gene integration into the germline seems extremely costly and possibly unprovable. I mean, heck, there's at least one scientifically proven case of a virgin birth.[1] Where does that leave us?

I return to my original point: Demanding perfection [and omniscience] is unreasonable and unnecessary. All of these other concerns are typical of any medical procedure: you attempt as best you can to integrate known risks as well as unknowns (known unknowns and unknown unknowns) into a cost and you compare it to the benefit, and if the benefit outweighs the cost then go for it. For germline editing in particular the costs will likely outweigh the potential benefits in most cases for some time, but we still need to make that determination regularly, honestly, and in context (actual proposed cases), without our fingers on the scale.

Issues like consent are ancillary. And they exist regardless of gene therapy. People don't consent to be born. Or consent to be "identified" through family members choosing to publish their genetic information. Social engineering experiments have lead to holocausts, even when they began innocently; if you go back far enough in the causal chain, they're all innocent and completely unintended. These problems, high-stakes consequences, and paradoxes already exist; we already struggle with them. Gene therapy, not even germline therapy, create fundamentally de novo issues. That's the real hubris, the delusion that we're not already playing with fire.

At the end of the day what the Chinese researcher did was reprehensible, but mostly for very particular reasons. I'd wager big money that a significant plurality of medical scientists, if not a majority, are today already prepared to approve germline editing given a good candidate therapy--patient, vector, payload, etc. As for medical ethicists, as scholars they tend to splinter into radical advocates or skeptics because that's how you get tenure and attention; and unlike doctors they don't get fired (or "disappeared") when they're wrong.

[1] "Oral conception. Impregnation via the proximal gastrointestinal tract in a patient with an aplastic distal vagina. Case report", http://img2.timg.co.il/CommunaFiles/21227065.pdf

[ak217]

The original point of yours that I find issue with was about "perhaps why most scientists are less concerned", which is really bullshit because most scientists in the field are concerned about premature germline editing. And the arguments you've arrived to in support of it rest on a bunch of false equivalences.

[wahern]

I never said not concerned, I said less concerned relative to the apparent concern in the comment I was replying to. Any error would be in the relative level of concern.

I know of their concerns. A friend of mine just got his Ph.D and has a very interesting story about how he answered a query by one of the CRISPR patent holders (then a student in his program) regarding techniques for delivering an intact sequence to the mammalian nucleus.[1] Prior to graduate school my friend spent several years working at the Craig Venter institute studying rhinovirus (while his wife completed her post-graduate work at NIH), and the technique he utilized at the institute and recommended "coincidentally" ended up being the one used. Which gives credence to the whole argument that the CRISPR "discovery" was basically combining together two already well-established methods for gene editing in an obvious way.

Also, he was the safety directory in his lab, both at school and at the institute. Because of the nature of the work, he would obviously be well aware of the risks involved with any sort of gene therapy. I don't know whether he would approve of germline therapy, but I'm pretty sure he'd agree that any blanket ban with the pretense of saving humanity would be naive as it's quite likely already happening to some extent under the radar, both deliberately and unintentionally. But that's a different sort of argument and doesn't contradict what yours, as far as I understand it.

I just took your argument as being excessively alarmist, and my point boils down to that scientists tend to be less alarmist because they're already inured to these things. They know how the sausage is made, and it's never pretty. They see the enormous holes in knowledge that you can drive fleets of buses through. But they also understand that nature is far more forgiving than popular science journalism would have you believe. "Holy sh+t, I didn't expect that'd work as well as it did" is, I think, not an uncommon experience; likewise for "holy sh+t, that didn't go as I expected", for that matter.

[1] Or something to that effect. Don't quote me because (a) I'm recalling from memory, (b) he gave me the dumbed down version, and (c) a Harvard e-mail system migration meant that he lost all his previous correspondence so he's likewise recalling his discussion from memory.