Perspectives: no moratorium from organizers of #GeneEditSummit

Human gene editing green lightNicholas Wade Gene EditingI just got back from a historic summit on human genetic modification in Washington, D.C. New genetic modification technology, termed CRISPR-Cas9, has both made genetic modification a relatively simple matter for scientists and human genetic modification much more likely in the near future.

Heritable human genetic modification could prevent some rare genetic diseases so there is real potential there, but it also could open the door to serious problems such as unforeseen health consequences across generations, social justice issues, and eugenics. Both potential positives and negatives were discussed in depth at the summit. Keep in mind that most but not all genetic diseases already are preventable via existing technology that allows for genetic screening of unmodified human embryos.

I was there blogging the event (see posts here). My lab also works on genetics and genomics. We are using CRISPR for in vitro research on stem cells and cancer. The goal of the summit, held at the US National Academy of Sciences, was to chart a path forward on how science and scientists should handle the central question of whether to genetically modify humans and what considerations should go into such a decision.

The organizers of the summit tasked themselves more specifically with deciding whether to propose a moratorium on heritable human genetic modification. Several of them had in the previous months seemed to indicate support for something like a moratorium in public statements and interviews. However, at the end of the summit, the organizer’s statement did not take a decisive step. They only discouraged heritable human genetic modification. There was no recommendation for a ban or moratorium.

GMO Sapiens Front CoverIn fact, David Baltimore who served as Chair, said at the end of the meeting that they specifically were not endorsing a moratorium and that was a conscious decision. It’s not entirely clear though why they made this decision, which seems to leave the door somewhat open to making genetically modified humans. More on that in a bit.

My own perspective is that we need a moratorium of at least several years on clinical use of heritable human genetic modification technology so I am somewhat disappointed in the final summit statement.

Why am I concerned enough to be in favor of a clinical moratorium? I mentioned some of the risks earlier in this piece. You also can see my concerns articulated in more depth in my new educational book on human genetic modification (here; note that it is written for both lay and scientific audiences and if you are interested in getting it you can use discount code WS15XMAS30 to get 30% off) and in my new TEDxVienna talk.

The summit organizers had several options available to them on their statement. You can think of it with a stoplight analogy. They could have proposed a moratorium, or a red light. They could have wholly endorsed human genetic modification and given it a green light. In fact the headline of a news story (see image above) seems to suggest that they did do this, but that is incorrect and the actual body of that article correctly reflects that the organizers only endorsed continuing basic research, which I also support.

Another option was to make a yellow light statement something along the lines of proceed with caution. They didn’t do this either…at least not exactly. The organizers’ statement was more like an “orange light“, somewhere in between yellow and red. While they wrote that any attempts in the immediate future at heritable human genetic modification would be “irresponsible” they did not go so far as to say via a moratorium, “don’t do it”.

The vagueness to the public of the statement is further reflected in the fact that the headline of a story on the summit on the front page of the NY Times by Nicholas Wade got the gist of the summit statement exactly wrong and incorrectly said that the organizers did endorse a ban (see above).

Why did the organizers go for an orange light approach to germline human genetic modification?

Perhaps as a group this best represented their range of opinions. In other words, they themselves did not reach a consensus to have a moratorium. I didn’t sense that there was such a consensus overall at the whole summit either. Reaching a consensus in science can be extremely challenging so by their nature consensus statements may tend not to be decisive. I get that.ABCD Plan Human Germline Modification

One potential more practical reason for not proposing a moratorium is that the organizers firmly believe that germline human genetic modification will someday prove useful and desirable. I got that vibe from some of their talks as well as from those of other very influential parties at the meeting. In that hypothetical scenario, a moratorium today could be hard to reverse tomorrow (in the future). Perhaps they didn’t want to risk impeding the clinical translation of the technology in the future with a moratorium. However, a pause in human genetic modification need not have been onerous or long-term.

Another possible consideration for the organizers is that a clinical moratorium could have hypothetically also unintentionally discouraged human embryo gene editing research in the laboratory so this may be another reason for not pursuing a moratorium. Again like the organizers, I also support such research, but for me it should be on a limited basis with appropriate bioethics training, transparency, and oversight (see my ABCD plan).

In the end, the statement from the organizers would have been more effective if it had been far shorter, clearer, and understandable to the lay public. Perhaps they were most focused on sending a message to scientists who might be more likely to get the key points of the statement, but even so it would have been best to be understandable to all.

I hope that with continuing dialogue and meetings, which the organizers also rightly proposed, that this issue can be clarified further and that the public can be engaged at a far deeper level. However, there is strong urgency for action and clarity here, and the lack of a decisive statement from this unique meeting was a missed opportunity in that regard.

Time is short. The technology in this arena is advancing at warp speed, it is so ubiquitous, and there is such strong enthusiasm that we do not have the luxury of years to have more meetings and discussions, as much as they may be very important, without taking a clear stance.

The number one question I’m hearing today after the meeting is concerning: isn’t human heritable genetic modification now already inevitable?

NAS Meeting on Human Germline Modification Taking Shape

The US National Academy of Sciences (NAS) will hold a meeting on heritable human genetic modification on December 1-3, 2015 in Washington, D.C. Invitations to the NAS meeting to individuals starting going out last week.

The upcoming NAS meeting seeks to address these issues and discuss the possibility of a moratorium on clinical use of genetic modification technology. It could play a crucial role in shaping both national and global policy on human genetic modification.NAS gene editing

The meeting was sparked in part by rising concerns over the possibility that some scientists may race ahead to clinical use of new gene editing technologies such as CRISPR-Cas9. Such clinical use of human genetic modification technology could pose serious risks to both individuals and to science. Others have the opposite view and favor allowing heritable human editing to proceed as a natural course of science delineated only by existing regulations rather than a moratorium. An international meeting would have the goal to reach consensus on prudent policy in this area, just as the 1975 Asilomar meeting did on genetic engineering.

The NAS has announced that both the Royal Society and the Chinese Academy of Sciences are partnering on the new 2015 meeting. This is a positive step as it will increase the diverse, global views on the key issues. Leaders of both the new partners indicated their enthusiasm for the meeting:

“Human gene editing offers great promise for improving human health and well-being but it also raises significant ethical and societal issues,” said Royal Society President Paul Nurse.  “It is vital that we have a well-informed international debate about the potential benefits and risks, and this summit can hopefully set the tone for that discussion.”

Chinese Academy of Sciences President Chunli Bai said, “Both Chinese scientists and the government are aware of the pros and cons of human gene editing.  CAS scientists have organized a panel discussion and coordinated with related government agencies for regulatory policies on this issue.  We would like to work together with international communities for the proper regulation and application of such technology.”

One issue, however, is whether it could be a challenge for a meeting with such a broad spectrum of views and constituents to reach a focused consensus.

Details on the meeting are starting to come out on social media too.

Bioethicist Tetsuya Ishii tweeted about his invite to the meeting.

From the NAS website here are the meeting organizers:

  • David Baltimore (chair), president emeritus and Robert Andrews Millikan Professor of Biology, California Institute of Technology, Pasadena United States
  • Françoise Baylis, professor and Canada Research Chair in Bioethics and Philosophy, Dalhousie University, Nova Scotia Canada
  • Paul Berg, Robert W. and Vivian K. Cahill Professor Emeritus and director emeritus, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, Calif. United States
  • George Q. Daley, Samuel E. Lux IV Professor of Hematology and Oncology, and director, Stem Cell Transplantation Program, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston United States
  • Jennifer A. Doudna, investigator, Howard Hughes Medical Institute; and professor, department of molecular and cell biology, Lawrence Berkeley National Laboratory, and department of chemistry, University of California, Berkeley United States
  • Eric S. Lander, president and director, The Broad Institute of Harvard and MIT, Cambridge, Mass. United States
  • Robin Lovell-Badge, group leader and head, division of stem cell biology and developmental genetics, The Francis Crick Institute, London United Kingdom
  • Pilar Ossorio, professor of law and bioethics, University of Wisconsin; and ethics scholar, Morgridge Institute for Research, Madison United States
  • Duanqing Pei, professor and director general, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou China
  • Adrian Thrasher, professor of paediatric immunology, University College London United Kingdom
  • Ernst-Ludwig Winnacker, professor emeritus and director emeritus, Gene Center, Ludwig-Maximilians University, Munich Germany
  • Qi Zhou, professor and deputy director, Institute of Zoology, Chinese Academy of Sciences, Beijing China

Perspectives on Hinxton Human Germline Modification Statement

The international stem cell policy and ethics think tank, the Hinxton Group, weighed in yesterday on heritable human genetic modification with a new policy statement.

The Hinxton statement is in many ways in agreement with the Baltimore, et al. Nature paper proposing a “prudent path forward” for human germline genetic modification, which came out of the Napa Meeting earlier this year.

However, while several of the Napa authors have now thrown their public support behind a clinical pause or moratorium on heritable human modification (e.g. Jennifer Doudna as well as David Baltimore and Paul Berg in a later piece in the WSJ), Hinxton didn’t explicitly address either positively or negatively the question of a moratorium.Hinxton Group

My initial reading of the Hinxton statement is that I mostly agree with it. In my own proposed ABCD plan on human germline modification from earlier this year, however, I included at least a temporary clinical moratorium.

I also would have appreciated a more detailed risk-benefit analysis in the Hinxton statement. For instance, I didn’t see a discussion of specific possible risks in their statement. Via my own risk-benefit analysis, I come to the conclusion that on the whole a temporary clinical moratorium has the potential for far more benefit than harm.

What would be the specific, possible benefits of a moratorium?

If the scientific community has united behind a moratorium on clinical use not only will that discourage rogue or potentially ill-advised stabs at clinical use, but also if a few such dangerous efforts proceed anyway (which is fairly likely) and come to public light, these unfortunate events will be placed in the appropriate context of the scientific community having a moratorium in place. Therefore, a moratorium both discourages premature and dangerous clinical use as well as putting potential future human gene editing clinical mishaps into the proper context for the pubic.

Another potential benefit of a moratorium is that it could discourage lawmakers from passing reactionary, overly restrictive legislation that bans both clinical applications and important in vitro research. It would give the politicians and the public the right sense that the scientific community is handling this situation with appropriate caution. If you don’t think that a law on human germline modification is likely in the US, consider that conservative lawmakers have already proposed such a law be included as part of the pending appropriations bill and Congress a few months ago held a hearing on germline human modification.

Other benefits of a moratorium include that it would a) demonstrate to the public that the research community is capable of reaching consensus about important ethical issues and b) increase accountability within the research community. Any rogue researchers or clinicians who would violate the moratorium, even if it were not illegal for them to do so, would at least be subject to the disapproval and possible sanction of their professional peers or institutions. Without a moratorium in place, it is far less likely there would be these kinds of consequences.

What about risks to a clinical moratorium? The primary possible risk of a clinical moratorium is that it could, should human heritable genetic modification someday down the road be viewed as a wise course to pursue directly, impede clinical translation. This warrants discussion, but in my view the risk here is somewhat reduced by the possibility that continuing basic research develops a compelling case that a blanket clinical moratorium might no longer be needed.

The other risk here is that a moratorium on clinical use also might in theory discourage some potentially valuable pre-clinical research as well. In other words, some researchers may adopt the mindset that if they cannot get to their ultimate goal of making clinical impact, why do the preclinical studies? I expect that many researchers would instead go ahead and do the preclinical work with the expectation that a clinical moratorium could be lifted and in fact their own preclinical work might help build a case for moving beyond a moratorium.

I agree strongly with Hinxton on the need for continuation of basic science on CRISPR and other gene editing technologies limited to the lab. In my view, we should have a nuanced policy though, whereby we support continuation of gene editing research in human cells and even in some cases human embryos in the lab under specific conditions (see again my ABCD plan for details), but in which we also put an unambiguous hold on clinical applications at this time.

In the absence of a framework that includes a clinical moratorium, we probably do not have the luxury of a reasonably long time frame (e.g. measured in a few years) for open discussion to sort things out carefully. To be clear, open and diverse discussion is crucial, but we just do not have a whole lot of time to do it as things stand today. Why? In the mean time absent a moratorium, I believe that some will go ahead and do clinical experiments on human germline editing. This would not only put individual research subjects at risk, but also pose dangers in terms of public trust and support to the wider scientific community. In a relatively permissive environment lacking a clinical moratorium, one or two instances of rogue researchers clinically using gene editing in a heritable manner could end up leading to a backlash in which even in vitro gene editing research is stymied.

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.

Steven Pinker interview: case against bioethocrats & CRISPR germline ban

CRISPR-Cas9 gene editing technology is red-hot right now.

It has great power for research in the lab and there are hypothetical transformative clinical applications of CRISPR too. The latter efforts could include experimental attempts at reversal of disease-causing mutations in one-cell embryos with the hope that they then grow into full-fledged, healthy human beings. Hypothetically CRISPR could also be used for pursuing human enhancement via germline genetic modification.

As a tool CRISPR is exciting and my own lab is using it for genetic studies, but from a technical perspective it’s not perfect. It can introduce a range of types of errors into the genome, with largely unknown biological consequences. To date, the first and only report of CRISPR-based modification of human embryos was arguably most notable for the problems encountered including genetic errors. However, suboptimal CRISPR methods were used so better design would almost certainly reduce risks of errors.

CRISPR raises a number of questions and has sparked many discussions. How should we handle a cutting edge biotechnology of this kind as a community of scientists? What if anything should be the appropriate role of others in such considerations including bioethicists? Should there be a temporary moratorium on clinical use of CRISPR? I tackled some of these issues in my own past piece Practical Plan for Managing Human Germline Genetic Modification. Others advocate for a more liberal perspective on the road to possible clinical use of CRISPR, focusing on the potential for great benefits.

Overall, this all might be summed up as follows: how do we balance the gas pedal and the brakes on CRISPR’s use in humans to aim for the greatest overall net benefit?

Steven PinkerProfessor Steven Pinker of Harvard has been one of the most outspoken advocates for more gas and less brakes here. Both in writing and in talks he has expressed the view that we should move forward without substantial impediments to CRISPR-Cas9. For instance, Pinker’s “get out of the way” editorial last week in The Boston Globe on CRISPR was very critical of bioethics and advocated an expeditious path forward for the research without constraints. It sparked wide-ranging discussions and even some anger from bioethicists. Update: see also this brief reply to Pinker’s interview from noted bioethicist, Art Caplan.

A few days ago I reached out to Dr. Pinker to do an interview to learn more of the specifics about his views with a goal toward increasing dialogue. For instance, I wondered if he really felt that strongly about the harms caused by bioethics that were suggested in his editorial. I want to thank him for taking the time to provide such detailed answers that make the full depth of his views on these issues far clearer here than in the past.

Knoepfler. 1. Related to your talk at BEINGS and your more recent editorial, what do you see as the appropriate role for bioethics and bioethicists in the life sciences? “Get out of the way” seems rather absolute. Can you help us understand the nuances there in your view of bioethics if any?

Pinker: There’s a difference between ethics, on the one hand, and “bioethics” and “bioethicists,” on the other. Of course everything a scientist does—everything a human being does—ought to be ethically guided. But bioethics has become a professional guild that all too often impedes sound ethical concerns rather than advancing them. Many moral philosophers—the scholars who specialize in evaluating the soundness of ethical arguments—believe that mainstream bioethics commonly trades in confused claims based on emotion and woolly thinking (see these articles by Julian Savulescu, Sally Satel, and me for examples).

Take the very foundation of ethics. You’d think it would be an obvious ethical principle that life is better than death, health is better than disease, and vigor is better than disability. But, astonishingly, so-called bioethicists have repeatedly denied these truisms, either explicitly (in the case of the country’s former bioethicist-in-chief, Leon Kass, who argued that the desire to extend life is a sign of shallowness and immaturity), or implicitly, by fetishizing sweeping rubrics such as dignity, equity, social justice, sacredness, privacy, and consent at the expense of the health and lives of actual people.

It’s not just that many bioethicists practice bad moral philosophy. It’s that they are entangled in a conflict of interest. Institutionalized bioethics has become an academic and bureaucratic industry, and they need to rationalize their existence. You hardly need a bioethicist to tell you that it’s wrong to inject typhus into twins or to withhold antibiotics from syphilis patients. But to come up with an abstruse argument as to why a parent should be prohibited from saving the life of her infant by donating a part of her liver—for that you need a “bioethicist.”

Regarding my advice to “get out of the way,” the nuances were stated, albeit tersely, in the article. The first is that a truly ethical bioethics must weigh the benefits of any restriction on research against the harm that will be caused to the vast number of people who would benefit if the research proceeded expeditiously. Savulescu puts it starkly: “To delay by 1 year the development of a treatment that cures a lethal disease that kills 100,000 people per year is to be responsible for the deaths of those 100,000 people, even if you never see them.”

The second is that a truly ethical bioethics should justify any restrictions on research with rigorous, defensible arguments about benefit and harm, not with moralistic grandstanding, science fiction dystopias, perverse analogies to Nazis and nuclear weapons, esoteric theories pulled out of the air, or freak-show scenarios like armies of cloned Hitlers, people selling their eyeballs on eBay, or warehouses of zombies to supply people with spare organs—all of which I’ve heard in these debates.

And as I wrote, no one questions the need to protect patients and research subjects from exploitation or harm. If there are flaws in the existing safeguards, as, for example, Alice Dreger argues, the safeguards should be fine-tuned or re-engineered. This is not the same as giving more power to the bioethocrats. A great deal of bioethical argumentation has nothing to do with protecting people. It rather cooks up reasons why consenting adults should be prohibited from doing things that help them or others while harming no one—a prominent example being recipient-solicited or incentivized organ and tissue donation. And establishment bioethics has caused preventable harm. Most infamous is the case of Jesse Gelsinger, the young man who died in a Phase-1 trial of gene therapy in 1999. Common sense would say that the experimental therapy should have been tested for safety on infants with a severe form of the disease who would have died anyway. But Arthur Caplan, the country’s most famous bioethicist, argued that the parents of such infants would be so consumed with grief that they could not truly give consent—the kind of paternalistic argument that is all too common in this field—and that an 18-year-old with a mild form of the disease, who technically could give consent, should be enrolled instead. A strained interpretation of the magic word “consent” was allowed to trump expected harm and benefit, and the result was tragedy.

Today mainstream bioethics gets in the way on a massive scale. The most obvious example is Institutional Review Boards. They are blatant abridgments of free speech, convenient weapons for fanatics to wield against people whose opinions they don’t like, and high-volume red-tape dispensers which bog down research while being unnecessary or even harmful to the protection of patients and research subjects. (See the Illinois White Paper and American Association of University Professors reports on IRB mission creep, David Hyman’s “The Pathologies of Institutional Review Boards,” and the new books The Ethics Police by Robert Klitzman and The Censor’s Hand by Carl Schneider). Regulations on confidentiality and consent to use data and tissues have also gone way overboard. The future of medicine hinges on the use of massive, open-access datasets to find signals in the noise. If every byte has to be multiply certified for consent and privacy, or even destroyed after a few years, no matter how inconsequential to the person who contributed it, then huge numbers of future patients will suffer or will fail to be helped by our faulty knowledge of the real effects of treatments.

There is, to be sure, an important role for bioethics. Satel puts it well: bioethicists at their best are “scholars who study the intellectual and social history of value controversies in medicine and biotechnology. They can teach us about the technical and cultural antecedents of modern debates and show us how to engage in disciplined moral inquiry.  They are skilled at drawing conceptual maps of the dilemma at hand while enumerating various ways to resolve it.”

Knoepfler. 2. Forgetting bioethicists entirely for the moment, prominent scientists such as Jennifer Doudna, David Baltimore, and others have publicly called in unambiguous terms for at least a temporary moratorium on clinical applications of human germline editing technology. Do you disagree or agree? Why?

Pinker: Disagree. The specific harms they warn against, such as inducing cancer, mutations, or birth defects in the unborn child are already ruled out by a plethora of existing regulations and norms. Obviously we shouldn’t mess around with embryos in ways that have a significant probability of producing a sick or deformed child with no compensating benefit. But why do we need a new, across-the-board ban on an entire method to rule out what’s already ruled out on the uncontroversial grounds of protecting individuals against foreseeable harm? The authors seem to be acquiescing to the yuck-factor that surrounds the very idea of germline modification, if for no other reason than to draw a firewall around their own research programs, which are restricted to the genetic modification of somatic cells. But scientists should work to dismantle irrational taboos, not indulge them.

First, the idea that there is some sacrosanct entity called “the human germline,” such that deliberately manipulating it would violate this sanctity, or restrict the freedom of future generations, or alter the species in unprecedented and frightening ways, is biological nonsense. No two people, not even monozygotic twins, have the same germline. Each of us introduces dozens of random mutations into our germlines, often multiplied by voluntary choices such as exposing ourselves to mutagens like tobacco smoke or fathering a child in middle age. And we affect the genetic makeup of our offspring, and the species, every time we choose to have unprotected sex with one partner rather than another. So even if it did come to pass that some people edited out disease genes, or (far less likely—see below) edited in enhancement genes, it would be a droplet in the maelstrom of naturally churning genomes.

Second, a ban or moratorium would only reinforce the pernicious aura of dread that surrounds genomic modifications. This is the dread that incites across-the-board opposition to genetically modified organisms and that underpins the bogus moral arguments against cytoplasmic donation for mitochondrial disease (the so-called three-parent babies—another case in which so-called bioethical concerns increase rather than decrease death and suffering). And the spurious ideal of germline sacredness could compromise the treatment of disease in other ways. Though lots of things went wrong in the Gelsinger case, one complication was the decision to administer massive doses of the viral vector directly to his liver, with the risk of lethal inflammation, rather than systemically, out of the fear that (God forbid!) it might introduce the needed gene into his sperm-forming cells. That’s probably not what killed Gelsinger, but it did kill a monkey in a safety trial, and this germlinophobia could certainly endanger gene-therapy patients in the future.

Third, germline editing could have direct benefits in a number of scenarios: to parents with disease genes who don’t produce enough viable embryos for preimplantation genetic diagnosis (especially when more than one such gene is involved, which multiplies the number of necessary embryos); to parents who both are homozygous for some recessive disease gene (not far-fetched given how often people meet each other through support groups); if future data were to show that PGD babies have compromised longevity or health; and in other scenarios that perhaps we can’t imagine. For these reasons Savulescu, with Chris Gyngell, and Henry Miller with Drew Kershen argue that research on germline editing is not only morally permissible but morally imperative.

Knoepfler. 3. You appear relatively confident in future benefits of new biotechnology such as CRISPR to millions of people, but you seem very skeptical of the risk predictions that you described as “speculative harms”. What makes you so confident of benefit and at the same time so skeptical of risks? If us humans struggle generally at accurately predicting outcomes of biomedical science, why should there be a more accurate expectation of benefits as opposed to risks?

Pinker: No, this is wrong. Though it’s certain that the biomedical research enterprise as a whole will deliver benefits to billions of people, we can have no such confidence in particular technologies. That’s why we need a diversified research portfolio, without arbitrary bans. If you ban something, the probability that people will benefit is zero. If you don’t ban it, the probability is greater than zero.

As for the potential harms, they are far too nebulous to justify a ban or moratorium. Far from being confident in the power of gene editing, I’m on the record as being skeptical that we’ll ever see genetic enhancement of babies—the outcome that the prohibitionists and moratoristas dread and that many bioethicists blithely assume is inevitable. (For example, in 1999 Caplan announced that before the end of this century “We will see many children made by the artificial creation of embryos…This prediction is 100 percent certain.”) The prophesy of designer babies ought to be a relic of the early 1990s, when people thought there was “A Gene For” this or that talent. We now know that heritable psychological traits such as intelligence and personality are the product of hundreds or thousands of genes, each with a tiny effect, many of which may have harmful effects as well, such as an increased risk of neurological disease or cancer. With each enhancement gene providing a nugatory benefit and a non-negligible risk, and with the editing process itself imposing risks, it’s unlikely that today’s morbidly risk-averse helicopter parents will take a chance at enhancing a child—they won’t even feed their babies genetically modified applesauce! And that’s assuming that such a procedure ever got to the point of clearing conventional safety hurdles, which is far from likely. Add these risks to the fantastic expense and tribulation of IVF compared to good old-fashioned sex, and one should conclude that widespread genetic enhancement is too unlikely a possibility to worry about. And that’s assuming we should worry at all. There is, in addition, the argument (from Savulescu, the transhumanists, and others) that if enhancement were ever feasible it would be a good thing, not a bad thing—or at least a matter of individual freedom rather than government coercion.

Now, the story is different for editing out disease genes. There are more ways that a complex system can break down than that it can work better, and it’s easier to fix a defect than engineer in an improvement. Also, the benefits are very different for preventing death and disease (huge) than for implementing an enhancement (minor). So the possibility that germ-line editing might prevent disease in the future is well worth exploring.

Knoepfler. 4. Congress recently held a public hearing on human germline modification and is considering a legal provision to block editing of human embryos. What do you think of having such a hearing and the possibility of a restrictive legal provision? You said to bioethics, “get out of the way”. Should we scientists say the same thing to lawmakers? Why?

Knoepfler. 5. There is likely to be a NAS meeting sometime late this year on human germline modification by such technology as CRISPR-Cas9 and mitochondrial transfer (3-person IVF) in the spirit of the 1975 Asilomar meeting. Do you think this new meeting will achieve positive outcomes such as a white paper that appropriately has a vision for the future? What if the consensus is for a moratorium? Could you support that?

Pinker: I’ll answer these together. I think that scientists should reiterate the principle that no experiment should be permitted which imposes an unreasonable risk of an illness or birth defect on an individual. But no, I don’t think that scientists should support a ban or moratorium on germline genetic editing, for the reasons I set out in my answers to questions 2 and 3. Though the Asilomar recommendations have long been a source of self-congratulation among scientists, they were opposed by a number of geneticists at the time, who correctly argued that they were an overreaction which would needlessly encumber and delay important research. And the journalist Victor McElheny reminds us that the recommendations sowed a panic which came perilously close to shutting down some of the nation’s major laboratories, a danger he argues we are now in danger of repeating.

That having been said, I recognize that the political arena follows different rules than scientific and intellectual discourse. The scientists who lead major research institutions and deal with politicians and other public figures have to master the arts of compromise, tact, euphemism, and strategic deal-cutting. That’s how democracy works, and I’m grateful to the scientific leaders who carve out a space in which the rest of us can flourish. There are things they may believe but can’t say. But it’s important that someone says them, and that’s how I see my role in these debates.