National Academies panel leaves door a crack open to future human genetic modification

Early human embryosA National Academies panel on human genome editing chaired by Alta Charo and Richard Hynes released its report today. While it covered both somatic and germline (heritable) human genetic modification, the latter topic is far more contentious. You can see the National Academies summary of their report here. You can read the full report here.

On germline genetic modification using technologies such as CRISPR, the authors of the report carefully discussed potential benefits and risks to the use of this technology. On my first brief reading of it, the report is mostly appropriately cautious in terms of outlining the potential risks as well as societal and bioethical issues in addition to potential benefits.

As to the more controversial area of potential human germline genetic modification, I appreciate the fact that the report unambiguously says that human germline editing is not ready to be tried and lists numerous hurdles to address first. However, although the report tackles most of the key considerations and risks (and for that the authors should be commended), there is still an interesting undertone to the report’s discussion that seems to strive to justify leaving the door open to potential future use of human germline editing.

For instance, the report makes a point of noting mostly hypothetical instances where existing technologies such as PGD that are far less controversial may hypothetically fall down and so possibly might need to be supplanted by germline editing using techniques like CRISPR, but such instances are now and in the future would continue to be exceedingly rare. Too much weight are placed on these.

The other point that needs to be made is that hypothetical future germline editing in human embryos (or even done earlier developmentally in, for example, germ cells) with reproductive intent would have to be preceded by a great deal of research that involves PGD-like testing of human embryos to monitor efficiency and specificity of editing, chimerism, and other issues so it is not as though germline editing could avoid PGD-related issues or destruction of embryos.

I’m also not convinced that the personal need by some individuals to have a genetically-related offspring should be a major consideration in decisions related to the permissibility of human germline gene editing. The related concept of parental autonomy is given too much weight by the report. While this argument has both aspects that intuitively make good sense, it also has some that could lead to promotion of germline modification.

For instance, what if parents want their kids to have certain traits that become potentially available via germline modification? In this regard, the ability of researchers and policy-makers both in the US and more globally to prevent parents and practitioners from going down the path to use germline human modification for traits rather than strictly health conditions may prove to be quite limited and it’s not clear had to address that risk. The report in some places does not use strong enough language to counter the idea of human germline modification.

On the whole, I have favored a moratorium on germline modification, a step that this report does not take. Of course there are possible problems with a moratorium too including enforceability (lack thereof) and that once you have a moratorium it might be hard to escape it (e.g. if the government follows suit with legal steps) even if down the road the science were to back up getting rid of it. Note that as the report mentions, for at least some months longer, in the US the FDA cannot consider applications for any human embryo genetic modification and then there’s the Dickey-Wicker Amendment that disallows federal funding of anything that involves ‘destruction’ of human embryos and such things as using CRISPR modified embryos to do PCR for research would qualify as destruction. But then there’s loads of private money out there for research as well.

What are your impressions of the report?

For more of my thoughts and concerns on human genetic modification you can read my book GMO Sapiens and watch my TED talk (below).

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?