October 24, 2020

The Niche

Knoepfler lab stem cell blog

New human genome editing (HHGE) academy report: solid, but key gaps

Something called, “The International Commission on the Clinical Use of Human Germline Genome Editing” has issued a new report on heritable human genome editing (HHGE). The Commission was convened by the U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the U.K.’s Royal Society. This post is my initial take on the summary of the lengthy report. I hope to have time to read the full report in coming weeks and it’s possible some new perspectives may emerge. Here is my thinking as to the summary.

11 HHGE recommendations: solid, well thought out

Generally, the 11 recommendations  regarding HHGE made by the Commission seem logical and carefully thought out. The Commission gave due consideration to the main technical considerations.

The International Commission on the Clinical Use of Human Germline Genome Editing HHGE
The International Commission on the Clinical Use of Human Germline Genome Editing or HHGE.
There’s a good balance in the recommendations of having international bodies providing guidelines and input, while there’s a dose of realism that often it will be individual countries making their own decisions about how to handle HHGE. Here is my very brief outline of the 11 recommendations:
  1. Do not attempt to make a gene-edited baby because we’re not ready technically
  2. Societal dialogue is needed before moving forward as well
  3. There are so many potential uses of HHGE that one path cannot be a universal framework
  4. Criteria for potential uses such as for severe genetic diseases, including not editing WT embryos
  5. Do not proceed in the future until there is compelling preclinical evidence of safety and efficacy
  6. You need a plan for evaluating embryos in the pipeline to potential implantation
  7. Continue research on making gametes from stem cells
  8. Countries considering proceeding with HHGE should have regulatory bodies and frameworks in place to evaluate and if it proceeds, to oversee the process
  9. An International Scientific Advisory Panel (ISAP) should be established to stay on top of the main issues and advances, and the ISAP can advise countries on where things stand. (who’s going to decide who is on the panel?)
  10. A second international body should be established to provide recommendations. (what’s the difference between the panels? The second one has more impact?)
  11. An international mechanism should be in place to field reports of deviations from standards or other concerns on HHGE research.

Gaps in the report

Are technical challenges unresolvable?

I wonder whether the technical hurdles like mosaicism and reducing the risk of deleterious on- and off-target effects can ever be overcome satisfactorily. In my view, the report summary should have been more direct about just how difficult these challenges will be and raise the possibility that they may never be resolved.

Societal, social justice, and ethical issues

The report also sidesteps non-scientific issues that are nonetheless crucial. In this way the report is more focused on “can” we do this and less on “should” we do this.

Looking ahead, idea of a temporary moratorium, & designer babies

He Jiankui
He Jiankui, who claims he made CRISPR’d babies and is now apparently serving a prison sentence.

More broadly, I personally still feel that a temporary moratorium on HHGE is our best bet for the next 3-5 years. The actions of He Jiankui (making at least two and probably three babies with CRISPR who may face health problems due to the reckless nature of the gene edits) and his prison sentence have practically-speaking made it far less likely that someone else will go rogue, but a temporary moratorium poses little risk and could help in some ways.

The report also has an undertone that there are going to be unique, important roles for HHGE to fill that pre-implantation embryo screening cannot achieve. I’m still not convinced that’s going to be the case to a sufficient degree to warrant the risks of continuing HHGE. I also worry about potential side paths using CRISPR to designer babies. I addressed many of these issues in my book, GMO Sapiens. Check it out.