Table 1 Quotations that illustrate theme 1

1

Dealing with uncertainty

Identifying sources of uncertainty

1A

More experimental evidence must be obtained

R1: “Various designs (..) work mathematically. But sometimes biology is different than theory. So these models should be tested experimentally in the laboratory the upcoming years”

1B

Knowledge gaps

R21: “There’s a lot we don’t know right now and there’s much more study that needs to go, that needs to happen before we start releasing gene drives into the environment”

1C

Technical hurdles

R26: “All these proof of principle drives that have been published, they’re (..) very gentle to the genome, which means that they’re easy to show good principals in the lab, but they’re not strong enough to be able to spread robustly once you get them into the wild. And so yes, the issue we’re encountering now is—we know how in theory we should build them—to make them spread strongly in the wild. But there’s just so many engineering hurdles to get that to work, right”

1D

Translation from laboratory to field

R6: “There are so many idealizations in populations genetics models that I would not want to stake a whole lot on them being accurate predictors of what happens when you intervene [in the wild]”

Dealing with epistemic uncertainty

1E

Epistemic uncertainty as a reason to support a moratorium

R29: “I think in terms of the moratorium scientists are not even at the stage yet of asking the right questions about gene drives, let alone building enough understanding of genes and evolution to release gene drives into the environment”

1F

Epistemic uncertainty as a reason to support phased research in light of the status quo

R12: “(..) the status quo situation we find ourselves in is already attended by significant harms. That’s certainly the case with malaria. (..) [and so] I think we ought to push back a little against this overly precautious approach. And that’s not to say I’m going to absolutely support releasing (..) [a] gene drive organism. But I think in order to make an informed decision about whether we should be doing field trials or more general releases, we really need to know more about what the technology can and can’t do”

1G

Accepting a certain level of epistemic uncertainty

R14: “There are many, many reasons why it might fail in the field (..) but there’s a certain point where we have to say “it’s good enough and we can’t see any obvious reason why it’s going to fail”

1H

Efforts undertaken to study knowledge gaps should be acknowledged

R31: “It never ceases to amaze me that these things are still years away from actual release and yet they’re in the focus of such an intense scrutiny already, and a lot of the questions raised are questions that we’re really trying hard to answer and would not go to the field without answering. But, you know, it is bound to cause confusion with the public that we can’t answer them yet. (..) It’s going to take a while to answer these questions and, in the meantime, the public is getting hit with this uncertainty, uncertainty, uncertainty, and so it’s complicated”

1I

Justifying a ‘leap of faith’

R12: “The big question is going to be when we have to consider potential harms to ecosystems because that’s obviously something that’s quite difficult to model in constrained environments. So that’s going to be the leap of faith at the moment. (..) we’re going to have to again, make a balance to think: what are the kinds of important interests that might justify the leap of faith? (..) My view is that (..) it’s going to depend on the degree to which the benefit (..) plays a central role in either human wellbeing or the wellbeing of other features in our environment, including animals”

Importance of setting realistic expectations

1J

Overhyping may block further development at a later point

R14: “There’s a genuine risk that we put too much hope and faith in gene drives and that they don’t work very well. (..) people need to have a realistic view of what could happen after a gene drive release. And that we don’t have an expectation that the gene drive is released and it’s the first one and we, you know, are still trying to understand how it might spread, how population dynamics come into it, and migration of the mosquitoes, and seasonal effects. And it spreads for a short while and then fails because something stops it from spreading farther. (..) if these things happen, I don’t think that should be a block to further development”

1K

Overhyping creates a false dichotomy

R32: “This silver bullet narrative is damaging. (..) if you propose something as a silver bullet, then you’re somehow some sort of [curse word] if you decide not to use it if it could be this cure-all. We don’t even know if it is, you know? (..) it promotes this binary discussion of “okay, fine, if you don’t use it you want all these people to die (..) and no, that’s not it. (..) I don’t want children to be dying either, but I also don’t want us to make decisions based on something like, someone’s crazy vision of something that maybe isn’t necessarily true yet. We don’t know if it is”