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).

Top 20 Stem Cell Predictions for 2017

stem cell crystal ball

Stem cell crystal ball

Each year I make a list of predictions for the stem cell and regenerative medicine field for the coming new year. Later in this post I list my top 20 stem cell predictions for 2017. In looking at my past predictions I realized this will now be my 7th year doing stem cell/regenerative medicine yearly predictions.

You can see below links to these predictions for past years, which sometimes seems rather far removed from today and in other cases strike me as strangely apropos of our times.

What will 2017 bring? Below are my top 20 predictions in no particular order except starting with a few hopeful visions for the coming year.

Continue reading

Korean edition of my GMO book on human CRISPR is out

I got a package from my publisher and upon opening it I saw the Korean edition of my book GMO Sapiens on the potential use of CRISPR in humans. The English language edition can be purchased here at the publisher where you can get 35% using the discount code WS16XMAS35 until January 15th or here on Amazon.gmo-sapiens-korean

This is really exciting.

I don’t speak Korean, but it was interesting to see the cover and how the book turned out in Korean. The cover art on the Korean edition is quite striking with the silver and red, and the different icons coming together.

It is also a great feeling to know that many people in Korea or for whom Korean is a first language will be reading my work and thinking about the important issues involved.

New Paper on CRISPR of Human Embryos Highlights Serious Tech Problems

A new paper was recently published on CRISPR of human embryos for genetic modification. I’ve got to read this publication more carefully, but here’s a quick initial take on this human CRISPR 2.0 study.

The paper is Kang, et al. and is entitled “Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing”. This is only the second paper reporting genetic modification of human embryos. The first paper, also from China, created quite a stir last year and reported a lot of technical problems with the genetic modification of the human embryos.

Human embryo CRISPR

Part of Figure 1 from Kang, et al.

This new paper comes from a team led by Yong Fan from Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. The researchers focused on using CRISPR to try to create a specific form of the CCR5 gene allele called CCR5Δ32 that reduces human susceptibility to HIV. As in the first human embryo CRISPR paper, these scientists also used so-called 3PN human embryos that are generally believed to be non-viable. The point of the use of 3PN embryos is to reduce ethical concerns.

How did the CRISPR’ing of human embryos turn out this time?

In rare cases the team were able to create the CCR5Δ32 mutation within the human embryos (5-15%) and they did not observe in a limited screen any so-called off-target effects (i.e. CRISPR making edits in other genomic spots such as other genes where it might go). These are positive outcomes from the study. At the same time, however, they ran into trouble with another serious issue and that is that their approach more often than not led to the creation of other CCR5 mutations besides CCR5Δ32.

These other mutations called Indels were observed 36-63% of the time and could lead to complete inactivation of CCR5 or production of abnormal forms of the protein. CRISPR can lead to Indels instead of precise point mutations due to cells utilizing a specific type of DNA repair in response to cutting by Cas9 called non-homologous end joining.

In order for an attempt to make human embryos that bear CCR5Δ32 to be successful even in an in vitro experiment with no intent to produce a genetically modified person, you could not have the embryos have CCR5 Indels. It is also important to point out that the authors did not do whole genome sequencing to look for off-target effects, but only looked at a couple dozen or so predicted off-target sites. Furthermore, a successful production of CCR5Δ32 human embryos would need to have both CCR5 alleles get changed to have the CCR5Δ32 mutation. The authors did not find such homozygous CCR5Δ32 embryos had been created in their studies. Another problematic issue was that they observed evidence of mosaicism in these embryos as well.

Thinking about this in the big picture and longer term, the idea to change the CCR5 allele to make humans resist HIV infection would most likely invoke creation of a genetically modified person, but I suppose could also involve modifying blood cells ex vivo for subsequent infusion in more of a gene therapy approach.

Overall my quick first take on this paper is that more than anything it shows the many problems with hoping for success with this kind of research. The paper does not in my opinion strengthen the case that CRISPR’ing of human embryos with reproductive intent is ever something that could work well enough to be done clinically.

The authors seem to realize that and they write, “We believe that any attempt to generate genetically modified humans through the modification of early embryos needs to be strictly prohibited until we can resolve both ethical and scientific issues.”

The key word there seems to be “until”, which seems to leave the door open at least a crack.

I expect we will see many more papers like this one and frankly I’m not quite sure how I feel about that.

For my take on human genetic modification using CRISPR more broadly including the targeting of CCR5, check out my new book, GMO Sapiens.