Putting aside the concerns about potential backfire effects of unilateral action^[1], calling the release of gene drive mosquitoes "illegal" is unsubstantiated.  The claim that actually cashes out to is "every single country where Anopheles gambiae are a substantial vector for the spread of malaria has laws that narrowly prohibit the release of release of mosquitoes".  The alternative interpretation, that "every single country will stretch obviously unrelated laws as far as necessary to throw the book at you if you do this", may be true, but isn't very interesting, since that can be used as a fully general argument against doing anything ever.^[2]

1. ^{^}

   Which I'm inclined to agree with, though notably I haven't actually seen a cost/benefit analysis from any of those sources.

2. ^{^}

   Though you're more likely to have the book thrown at you for some things than for others, and it'd be silly to deny that we have non-zero information about what those things are in advance.  I still think the distinction is substantial.

Unilateral action in general might be bad, but most of these reasons you've given to not support an illegal one (if gene drives were explicitly illegal, which they're not) seem completely misguided or misleading. I can't parse whether or not this is deliberate. I'm against lying as a means of stopping unilateral action in most real world scenarios; people who want to obtain or give multilateral consensus will need to understand where actual risks come from, not made up risks designed to discourage bad actors.

Eradication of malaria will require a lot more than a gene drive against Anopheles gambiae s.l., meaning government cooperation is still required.

AFAICT this is basically incorrect. What government cooperation do you suspect is necessary? You have to release a "significant amount" of mosquitoes across a "large enough" part of Africa, yes, but unless the local population is unusually isolated, the mosquitoes travel to other countries. Metacelsus estimates you could do it with maybe ~50k on a shoestring budget and most of the work would be catching the mosquitoes.

If what you really mean is "you have to not be actively hunted by every local government that has jurisdiction over a suitable place to start the gene drive" then A. that level of cooperation currently exists, and B. I think you are both underestimating the number of governments in Sub-Saharan Africa and overestimating their state capacity.

Resistance can and does develop to gene drives, so that development of better drives and coordinated support (massive releases, other simultaneous countermeasures, extremely broad coverage) are necessary to wipe out malaria in regions. This research will be set back or blocked by a release attempt.

Resistance may develop to the doublesex gene, and it may not. So far none of the trials done by Target Malaria have suggested this happens in practice. It is of course still theoretically possible, for that gene, that a resistance could develop at larger population sizes, which is one of the only good reasons why you shouldn't unilaterally release gene drive mosquitoes. But there are other gene drives you could deploy that would simply engineer mosquitoes not to transmit the parasite for malaria, so this is not a concern about gene drives in general, just the genes that introduce sterility.

Other than resistances, the claim "research will be set back or blocked by a release attempt" is also obviously incorrect. If you somehow only exterminate a completely isolated subsection of the larger population of Anopheles gambiae (which again, I find pretty unlikely) you can just try again. The Senegalese government is not going to both detect and then ban gene drives in response to a deployment that failed to reach escape velocity.

This could wreck the prospects for making additional gene drives for other malaria carrying mosquitoes, schistosomiasis causing worms, Tsetse flies causing trypanosomiasis, and other diseases, as well as agricultural applications. Collectively such setbacks could cost millions more lives than the lost lives from the delay now.

Read one way, this is a bizarrre technical misconception: the doublesex gene does not work on worms. A gene drive on Anopholese Gambiae would involve epsilon risk introducing a resistance on schistosomiasis causing worms.

Read another way:

There could be large spillover to other even more beneficial controversial biotechnologies outside of gene drives. The thalidomide scandal involved 10,000 pregnancies with death or deformity of the babies. But it led to the institution of more restrictive FDA (and analogs around the world imitating the FDA) regulation, which has by now cost many millions of lives, e.g. in slowing the creation of pharmaceuticals to prevent AIDS and Covid-19. A single death set back gene therapy for decades. On the order of 70 million people die a year, and future controversial technologies like CRISPR therapies may reduce that by a lot more than malaria eradication.

The FDA does not, in fact, have jurisdiction over any of the places affected by the parasites you mentioned. The U.S. government has the money, political capital, and state capacity to start institutions like the FDA, Kenya generally does not. And the U.S. government generally starts deadly regulatory crazes like that in response to things happening to U.S. citizens, not Africans.

So, altogether, what you are proposing will/may happen if someone releases a gene drive to eradicate mosquitoes without getting "government permission" first is:

• It doesn't work.
• Even though it didn't work to kill mosquitoes, it, through a completely unspecified and at this point imaginary mechanical process, kills a small number of Kenyans, makes some women bear deformed children, etc.
• This negative side effect of the gene drive is somehow detected by either e.g. the Kenyan government or NGOs from first world countries.
• Those first world nations unanimously care enough about the death of ~1/10/100 Kenyans from a bad gene drive in Kenya to block CRISPR technology in agriculture, or maybe other third world nations unanimously care enough to proactively and effectively block further attempts to destroy other parasites.

In other words: Despite the fact that the biotechnology efforts to kill those parasites you mentioned do not currently exist, we're supposed to wait until 2030 to deploy the gene drive that stops malaria, because if they did exist they might be stopped in response to a side effect that does not sound mechanically possible and does not sound like it would be detected if it were possible. Pretty ridiculous IMO, even granting the (incorrect, but common on LessWrong) model of regulation that says the existence of FDA analogs is a result of every government "copying" the FDA, rather than normies just being extremely conservative when it comes to medicine as applied to humans.

This is frankly what jimrandhomh talks about when he says the safety concerns about "gene drives" are analogous to safety concerns about "nuclear power", in that they can't be addressed by science or policy predictions because they're actually anxieties provoked by the words "gene", "biotechnology", "unilateral", etc. Would you like to make some bets regarding this story? I'll give you great odds.

And this is all in addition to RobertM's obvious critique that releasing gene drives is not, in fact, actually illegal. I'm keeping Habryka's unilateral action clause, was always going to include some clause that says we're not going to pay out the bounty if it would mean pledgers get prosecuted, solely because more people are likely to be willing to pledge that way. These concerns do not seem to be coherent enough to merit amending the bounty otherwise.

That's too bad. I look forward to what you come up with, but I don't think I can offer any help :-/

Really sounds like learning some biology might be rather empowering lol. Noted.