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Physicist, Startup Founder, Blogger, Dad

Wednesday, November 28, 2018

He did it: He Jiankui talk at HKU conference on gene editing



This is He's talk from a conference on gene editing, in progress now in HK. (Should start at 1h09.)

This article describes serious discussions between He and bioethicists over the last year.

CapEx required for this process is quite modest -- not beyond the capability of a medium-sized IVF clinic. The CRISPR vector was purchased, IIUC, for about $100!

The choice of CCR5 is not well motivated, from the perspective of most bioethicists: there are other ways to prevent HIV, and the edit could be regarded as an enhancement, not elimination of a disease allele.

@1h25 He claims that the parents were given the option to use unedited embryos for their pregnancy but chose to use the edited ones. (This decision was made even after being informed of the existence of a possible off-target edit in an inter-genic region. The possible off-target was not confirmed by later analysis.) If true, this has some important ethical implications. The problem becomes one of parental choice and reproductive freedom. IIUC, the father has rather strong feelings concerning HIV (being HIV positive) and the parents strongly desired HIV-resistance in their daughters. Who are we (or anyone else) to tell the parents whether to use the edited or unedited embryos?

Note it's possible I misunderstood what He said in his talk. There is a Twitter exegesis here, and a transcript here. I'm not sure I understood properly whether the intended edit was successful -- one embryo displayed mosaicism (not subsequently detected)?

Some comments I've shared with journalists and other interested parties below.
Re: Gene-editing using CRISPR, not a technical breakthrough -- it has been possible for some time. What is new is that someone had the audacity to push it to completion with human embryos. Some researchers who attended He's talk a few months ago at Cold Spring Harbor (the talk covered methodology but with no hint that real babies would be produced) found it sound but unremarkable.

In the near term most applications of CRISPR in IVF can already be accomplished simply by screening (genetic testing) against the undesirable genetic variant. No need to edit, just select one of the embryos without the variant.

With CRISPR one can potentially edit IN new genetic variants that neither parent has. This "enhancement" is much more ethically questionable, but may eventually happen. However it can only be done
with simple single-gene conditions.

Eventually we may have the technology to do multiple (hundreds?) of edits at a time, which will allow modification of polygenic traits. (Most traits are highly polygenic.) But this requires us to first identify actual causal variants (as opposed to variants used in a predictor that merely *correlate* strongly with the causal ones). This is a difficult scientific problem that may take a decade or more to solve. Predicting a complex trait is much easier than modifying it -- hence selection will dominate editing in utility for some time.

It is possible that gene editing will "normalize" selection of embryos as a less aggressive course of action!
See previous discussion Generation CRISPR?

At the same conference, George Daley, Dean of Harvard Medical School, advocates for a responsible pathway to clinical translation for gene editing.

George Church interview on what He did.

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