Where’s the Beef? Why I Disagree with 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.

12 thoughts on “Where’s the Beef? Why I Disagree with Pinker On CRISPR

  1. You criticise Pinker for not using data and reply with an appeal to authority (Doudna is concerned, therefore we should be concerned)?

    I think most people agree that the technology isn’t ready yet to make GM people tomorrow. Isn’t the ethical question about whether we should we ban germline editing once we are confident we can do it properly?

    Shouldn’t we continue with editing experiments in non-viable embryos and find out if we can stop off-target activity? A moratorium only means we find out later

    • @Romulus,
      Thanks for your comment.
      I do admittedly think that Doudna is an authority along with others such as Baltimore and their views and support of a moratorium on clinical use at this time is significant. As a scientist, I don’t see anything wrong with giving special weight to authorities and scholars, but is that considered a misstep in the bioethics/philosophy world?
      I also point out that the body of data that we currently have is (A) insufficient to support clinical use, and (B) points to specific challenges to be overcome.
      My view is that in this context and given this situation with the data, a temporary moratorium on clinical use would be appropriate and beneficial in discouraging premature attempts at clinical use.
      The question of whether to continue with in vitro human embryo experiments is an important one. I have mixed feelings on it. On the one hand I’m supportive of the efforts to enhance knowledge, but on the other hand we have to ask ourselves what is unique that is being learned from such human embryo studies that couldn’t be learned from say using human somatic cells? I didn’t think, for example, that we learned much if anything of particular use from that first human embryo editing paper out of China, especially the way it was designed.
      I would support limited, in vitro human embryo studies under certain conditions (see my ABCD plan).http://www.ipscell.com/2015/03/abcd-plan/

  2. I find it extremely worrying that someone is “expressing concerns” as a support for your own position of enforcing a moratorium. I am also concerned about a lot of the issues brought to life by germline modification but I would not appreciate the expression of such concerns to be used as an argument for a moratorium.

    By using such dishonest citation techniques to support your arguments you achieve nothing but encouraging supporters of technology to hide any concerns as the expression of such will only be used as a tool against the technology.

  3. @Romulus,

    I take your point that the post we’re discussing, which IMO does make an important argument about data, is constructed with an unfortunate reliance on appeal to authority.

    Regarding “once we are confident we can do it properly”: Exactly who needs to be “confident”, in your view, before the technology is “ready […] to make GM people”?

    • @amateur,
      In science it’s considered fine and in fact logical to give weight to what scientific scholars and authorities believe. Perhaps in bioethics that is a no-no.

      At the same time, I stress that the most important thing is the scope of data (whether present or absent).

      The other thing to consider is that whether one likes to appeal to authority or not, practically speaking some individuals (e.g. those at the upcoming NAS meeting) will have decision making authority as well to propose policies (e.g. moratorium or no moratorium, if a moratorium then what kind, etc.) for the field of science as a whole. Those policies may not be binding, but they will be very influential on what actually happens.

  4. @ (amateur, ad-hoc) bioethics apologist

    Just as with other medical interventions, it’s the job of the FDA to decide if it’s safe or not.
    The ethical question of whether we should or shouldn’t do it is for society to answer. Unfortunately data is of limited use in ethical questions.

    • @Romulus,
      The FDA hasn’t been very proactive in these kinds of situations, particularly lately. They also do not have authority over in vitro human embryo experiments and if one or more research groups were to edit a human embryo and go ahead to implant it, and create a GM person, the FDA could only function reactively in such a case and it could take a very long time to do so. Of course the FDA also only has authority in the US.
      My response to Pinker was as a scientist and Pinker is not a bioethicist either. He’s an experimental psychologist. Data is definitely relevant to bioethical discussions.

  5. @admin,

    To me, this approach would have been more compelling:

    1. “Doudna has publicly voiced the following specific concerns […]. These concerns lead me to support a moratorium because […].”

    That formulation steers explicitly clear of the meaning I think you did not intend (but which I think other commenters may have perceived),

    2. “We should have a moratorium because Doudna is concerned.”

    I think an argument like (1) is always superior to an argument like (2). In fact, I have a tendency to reject (2) out-of-hand… which sometimes leads me to *my own* fallacy: “The argument for X is invalid, therefore X is false.”

    Likewise, I hope for care with such broad assertions as “In science it’s considered fine and in fact logical to give weight to what scientific scholars and authorities believe.” You pointed out in your post above that it is important to seek hard data and sound reasoning. Expert opinion may guide the search (I trust that was your intended meaning), but I think it ought not be accepted on the basis of blind faith in its source.

    See also the Wikipedia entry for “appeal to authority”. It even has some examples from academia. The bit about counting chromosomes may already be familiar to folks associated with this web site.

    In any case, despite my continued remarks in this line, I hope none of this aside becomes a distraction from your main point. For me personally, when I read about the technology at hand here, I find myself thinking, “look before you leap.”

  6. Paul,

    Why do you think Doudna is an authority on this?

    For that reason, why do you consider Berg and Baltimore authorities on this as well?

    (admittedly, Doudna is more qualified in my view than either of them, but that’s solely because her lab works on Cas9)

    Ceding authority to someone solely because their lab demonstrated it first is dangerous to me. I would be asking the same questions regardless of who you put up here, be it George Church, Feng Zhang, Catherine High, etc. Too much of the discussion (with the exception of the gene drives) centers around off-targeting, which has failed to be significant outside of HEK293T cells and U2OS cells.

    My understanding was that logical fallacies were generally frowned upon in bioscience as well, but I may just be wishing that it were so.

  7. Your critics on professor Steven Pinker is reasonable I think. Especially, I agree that our decisions need to be in large part driven by data and even by the absence of data.

  8. I think it’s wise for scientists, as a group, to think about the implications of their science and try to prevent serious accidental consequences.

    But I very much worry about interference based on so-called bio-ethics. That’s because, just as Dr. Pinker has pointed out, there’s a very bad prior record of bio-ethecists, self proclaimed, making seriously unethical pronouncements.

    I remember, not very long ago, a case where a child had a disease requiring an organ transplant, one of those organs we each have two of, and the parents wanting to have another child who could then be an organ donor. The bio-ethical pronouncement was that it would be unethical because the second child could not give informed consent for such an organ donation. Somehow, the controlling ethical principle was that it is better to deprive the second child of any life at all, while condemning the first child to early death. Try as I might, I could not understand how this was a moral choice. It seemed to me that the parents were much more able to make an ethical choice than those pompous bio-ethics experts..

    Also not too long ago I saw the bioethics debate about whether a mitochondrial transplant, to allow parents with a rare mitochondrial disease to have a healthy child, should be seen as “genetic tinkering”. Mitochondria have the moral status of organs, and a mitochondrial transplant is no more “genetic tinkering” than is a blood transfusion.

    Until the field of bio-ethics can clean its house of such arrogant tomfoolery, we should indeed ignore its pronouncements and develop our own institutions for safety – just as the geneticists did in 1975.

  9. “we should… develop our own institutions for safety – just as the geneticists did in 1975.”

    You would agree then that an ethical moratorium on some experiments is acceptable if professional biologists, physicians and lawyers agree? This is what happened at the Asilomar Conference in 1975.

    That type of forum is inevitable for each of the issues discussed here, but in the modern era we need more than just geneticists, we need politicians, the public and industry at the table – as long as these representatives are fully aware of the technical aspects and their consequences, they have every right to comment. Ethical issues in science is not an area where scientists should be making recommendations alone.

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