October 25, 2020

The Niche

Knoepfler lab stem cell blog

Why I Disagree with Steven Pinker On CRISPR

Steve PinkerProfessor Steven Pinker of Harvard has been making the case recently that when it comes to novel biotechnologies such as CRISPR-Cas9 that bioethics should just get out of the way. Further, he has argued that we do not need a moratorium on clinical use of CRISPR-Cas9 for human genetic modification. In fact, he says that such a moratorium would be harmful.

I think he’s wrong about that. I’m not a bioethicist so rather than talk primarily about his views on bioethics, I’m going to focus instead on a scientist’s perspective on the key issues.

I respect Pinker’s intellect. In addition, I share his goal of stimulating dialogue on innovative biotechnologies. Sometimes being provocative is the best way to stimulate much-needed discussion.

I invited Pinker to do an interview on this blog last week, which you can read here. In that conversation he goes into much more depth on his view of human genetic modification via CRISPR, a possible moratorium on such efforts (which again he strongly opposes), and bioethics. It’s a fascinating read even if you disagree with him.

His is a wonderful, bright writing style and I appreciate his inventive neologisms like the new words bioethocrats and moratoristas even if admittedly (we need thick skins to weigh into science politics) they tend toward the pejorative and arguably are divisive.

The real Achilles heel of his argument on human germline modification is the lack of hard science behind it. As a spin on “where’s the beef?” we might ask Pinker, “where’s the data?” In fact, his main assertions are not backed up with data, but rather with assumptions, predictions and clever use of words. Most scientists that I know aren’t convinced by this kind of argument because there’s not much if any data behind it. The arguments are not scientific, but more philosophical and speculative.

For instance, his super cheery vision on biotech and in particular clinical use of CRISPR puts him at odds with leaders in the gene editing field including scholarly scientists such as Jennifer Doudna. Doudna and other prominent scientists have publicly voiced concerns over the potential for misuse of and unintended consequences from CRISPR-Cas9.

Doudna and fellow scientists such as Nobel Laureates David Baltimore and Paul Berg correctly see there being great potential for good in CRISPR-Cas9 and I totally agree on that, but Doudna, even as a discoverer of CRISPR-Cas9, doesn’t view this technology as being free from complications or bioethical issues. Of course she’s right about that too. Even geneticist and CRISPR-Cas9 innovator George Church, who has been relatively more enthusiastic about the possible future role for heritable human modification via CRISPR, has raised some concerns at times about this technology including safety and possible weaponization. Those issues plus many others including commercialization and potential conflicts of interest, are precisely where we scientists need the expertise of bioethicists. But really what the scientists like to focus on is data and that’s one major thing lacking from Pinker’s argument.

Biotechnology is neither as simple nor as positive as over-exuberant technophiles would have us believe. In the real world of science, things are complicated. Experiments are rarely black and white in this arena where grey dominates. We might say, “Data is king” and data are glaringly absent from the writings of those promoting human genetic modification. For instance, Pinker hasn’t presented data to back up his sweeping assertions that (A) we can do a risk-benefit calculation for innovative biotechnologies such as CRISPR-Cas9 and that (B) as a result we can confidently predict that benefits will greatly outweigh risks. He’s engaging largely in wishful thinking. I pressed him on this point in my interview and I don’t believe he answered that question convincingly. In addition, Pinker is far too optimistic about the protections in place for individuals or future individuals who might be genetically modified and harmed in the process.

As a scientist and an admitted datacrat, I have to look skeptically on this kind of breathless optimism in the process of policy formation. The fact that the CRISPR-Cas9 data we have so far is at least somewhat concerning on certain levels is certainly relevant here as well and concretely supports a moratorium. These data include the evidence of substantial off-target activity of CRISPR at times, that CRISPR can also make the “wrong” genetic modification in the “right” place too, the fact that CRISPR technology is new and rapidly improving giving a sound, data-based basis for predicting that even in a few years CRISPR-Cas9 will be a dramatically better tool than it is today, the reality that the first paper reporting CRISPR editing of a human embryo used a suboptimal form of the technology (i.e. human judgment is not perfect even in science), and more.

We can argue about philosophy and debate about future visions. We can battle with words. In the end, our decisions need to be in large part driven by data and even by the absence of data. For example, scientists can say, “we need to know XYZ before we can proceed, but we just don’t know that yet”. More data is definitely needed before we can confidently make predictions about CRISPR’s use in humans.

Further, bioethicists have a key, positive role to play here in community discussion and policy formulation even as we take the appropriate time to accumulate more data. I would hazard to guess that most scientists (and I include myself in that) wouldn’t want bioethicists to completely run the show on this, but at the same time we realize that we need some bioethics expertise around the table. That certainly was the case for the Napa meeting on CRISPR. I’m confident that the organizers of the upcoming NAS meeting on human germline modification share this view too so I’m not going to belabor that point.

The bottom line is that the keys to a constructive path forward on CRISPR-Cas9 and evaluation of potential human genetic modification overall will be more data as well as balance in discussion and policy making. We haven’t had time for that yet so at least a temporary clinical moratorium is the wise way to proceed.

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