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.

Baltimore, et al. propose path forward for human germline engineering in Science

In a new perspectives piece in Science, Nobel Laureate David Baltimore and co-authors including Jennifer Doudna and George Church, chart a potential path forward for human genomic engineering involving germline modification. See also accompanying Bioethics piece by Gretchen Vogel as well, “Embryo engineering alarm”.

human germline editing policy

In the piece, entitled “A prudent path forward for genomic engineering and germline gene modification” calls for further discussion and assessment of key potential benefits and risks to moving forward with this technology. The illustration included here is from the piece.

The piece is reflective to a large extent of conclusions from a recent meeting held in Napa on this issue.

The summary statement is as follows:  “A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed.”

They make 4 more specific recommendations.

  1. Strongly discourage clinical application of this technology at this time.
  2. Create forums for education and discussion
  3. Encourage open research to evaluate the utility of CRISPR-Cas9 technology for both human and nonhuman model systems.
  4. Hold an international meeting to consider these issues and possibly make policy recommendation.

This statement seems mostly in synch with the recently released ISSCR statement, but perhaps not quite as strong as it does not call for a moratorium on clinical use as ISSCR does and instead “strongly discourages” such applications.

In addition, this piece by Baltimore, et al. conveys more of a sense of optimism and somewhat of a more relatively positive vision that eventually CRISPR-Cas9 human germline editing might have safe, effective and ethical clinical applications. Even so they are relatively cautious about that possibility:

“At present, the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any at-tempts at human engineer-ing are sanctioned, if ever, for clinical testing.”

The full list of authors include David Baltimore, Paul Berg, Michael Botchan, Dana Carroll, R. Alta Charo, George Church, Jacob E. Corn, George Q. Daley, Jennifer A. Doudna, Marsha Fenner, Henry T. Greely, Martin Jinek, G. Steven Martin, Edward Penhoet, Jennifer Puck, Samuel H. Sternberg, Jonathan S. Weissman, and Keith R. Yamamoto.

One interesting thing to ponder is the potentially more diverse views amongst this list of scientists and bioethicists even though have come to a consensus clearly on key issues.

For example, in Vogel’s piece, Church is quoted with what might be viewed as somewhat of a dissent on at least one level:

“Those uncertainties, together with existing regulations, are sufficient to prevent responsible scientists from attempting any genetically altered babies, says George Church, a molecular geneticist at Harvard Medical School in Boston. Although he signed the Science commentary, he says the discussion “strikes me as a bit exaggerated.” He maintains that a de facto moratorium is in place for all technologies until they’re proven safe. “The challenge is to show that the benefits are greater than the risks.”

What are your thoughts on this new Science paper and the ISSCR statement, both out today?