September 26, 2020

The Niche

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George Church on Germline Human Genetic Modification

George Church
George Church on human CRISPR.

I recently interviewed leading genomics scientist George Church on the ways that trends in genomics are changing our world and the possibility of heritable human genetic modification.

His answers suggest that genomics and gene editing are poised to radically change our world and to literally change us.

Here’s the George Church interview you’ve all been waiting for.

Do you think the public is already shifting to be more accepting of genomic information as simply another useful part of their overall health profile rather than as some unusual kind of thing as it might have seemed only a few years ago? What’s driving this cultural change?

Church: Yes. Cost and quality.  Patients consider items that their physician offers — and genomics is becoming a more routine offering, due to cost and quality and steady expansion of the number of highly predictive and actionable tests.  I saw this personally in the routine options offered to my daughter (who has no known risk factors) when she became pregnant recently  — far beyond what would have been offered a few years ago to someone even with risk factors.

George Church Quote
George Church Quote.

What’s your view of 23andMe and other direct-to-consumer genetic testing/genomics companies? I’ve heard people predict that in the future people will share their genomes on Facebook-like social platforms or even on dating sites. Is there a possibility of the public getting too much genomic/genetic information about themselves or others without enough context? Should kids in school, perhaps as early as primary school, now start to be taught more about their genomes to help prepare the public for these big changes?

Church: Yes. There are now DTC whole genome sequences for as little as $650 (arep.med.harvard.edu/gmc/genome_services.html), and yes, I feel strongly that some minimum level of genetic literacy should be taught now in every year of school (even if only a few minutes per year).  This is a major objective of pgEd.org 

If technology such as Oxford Nanopore means that in coming years pretty much anybody can do DIY genomics on themselves, in their own backyard or across the world on a trip via a small disposable device and a laptop or even smart phone (e.g. “Genomics? Hey, there’s an iPhone App for that”), how will that change our world? Can we anticipate learning fundamentally new things via what some might say becomes the ultimate massive crowdsourced genomics experiments?

Church: Yes.  Oxford and Genia too.  In the same sense that ultrasound, X-ray and MRI allow us see inside living humans and microscopes enabled visualization and classification of microbial cells.  We will much better appreciate when we or others are infectious or just innocuously coughing.  And whether our food has pathogens, allergens, or personal risk factors. 

With gene therapy trials, human genetic modification is already ongoing. What about germline human genetic modification? Do you view that as a logical next step?

Church: I don’t think that germline is the next goal (nor next logical step), but it might be an acceptable side-effect of treating genetic diseases early, safely and effectively.  Many gene therapies currently in clinical trials are already aimed at young children to avoid permanent damage.  Treating sperm and eggs could reduce the number of abortions (spontaneous and induced) and the number embryos needed in IVF clinics.

Compared to non-heritable human genomic modification, do we need to think differently about heritable human genetic modification in some specific ways and if so, how?

**Any therapy done on healthy people will require more safety testing than a therapy designed for desperately ill people.  

Should we be talking about benefits and risks such as possible future genomics-based eugenics?

Church: Eugenics in USA from 1907 to 1981 involved government sterilization of 65,000 individuals to “improve” the gene pool.  The new technology enables parents to make choices about their children just as they might with Ritalin or cleft palate surgery to “improve” behavior or appearance.  To prevent such parental decisions, the government would again interfere with reproductive choice, but this time in the apparent opposite direction in terms of improving the gene pool.  To give the same name (eugenics) to these two scenarios seems unnecessarily confusing.   Should we be talking about benefits and risks?  Yes.  Frequently and engaging many voices.  

While here in the US the FDA wants more data likely to be obtained over the course of several years, the UK Parliament has forged ahead and just approved so-called “3-person IVF” in which the goal is to prevent mitochondrial disease, but at the same time the children produced will have in addition to the standard 2 nuclear parents, a “mitochondrial donor” as well so they will have genomic elements of 3 people including the donor’s mitochondrial genome. This appears to be the first example where heritable human genetic modification is codified. What’s your perspective on this development?

Church: It all boils down to “safety and efficacy” just like every other therapy, medical device and surgery.  This doesn’t seem like a good case for genetic exceptionalism. 

With CRISPR-Cas9 type of technology, the affordability of genomic sequencing, advances in cellular reprogramming, and reproductive cloning, is much more widespread genetic modification of various organisms on our planet inevitable? Desirable? I’ve read Austen Heinz say that we should “democratize creation”. What do you think of that concept? Will this be extended to human “creation”?

Church: Genetics is not new. Human creativity/creation is not new.  These have been ‘democratized’ for centuries, assuming that this means “accessible to many people”.   Regular folks choose mates for themselves and for other organisms, based on desired traits and this tends to work (hence the many breeds of animals and plants).  CRISPR might make the mutation part a bit easier, but the “selection” part of Darwinian (mutation/selection) is still the key effort.

I just saw this article “Engineering the Perfect Baby” in which Jennifer Doudna was quoted as calling for a temporary moratorium or “pause” on human germ line editing work. Could you please say if you agree or disagree on the call for a pause and explain why in either case?

Church: Note that the word “pause” is not in a quote from Jennifer.  I think that Hank, Jennifer and I agree that there should be caution and testing for safety and efficacy for all medical treatments.  This inevitably involves “pauses” during pre-clinical and phase 1 clinical trials. 

Also they said this in the piece:  “At meetings of groups of people known as “transhumanists,” who are interested in next steps for human evolution, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that, when people are born with them, give them extraordinary qualities or resistance to disease.” Can you comment on that?

Church: Note that throwing in the word “transhumanists” is unnecessarily confusing.  I use that slide at all sorts of meetings (none of them on “transhumanism”).  There may be transhumanists in the audience, but that is not the point.   The point is that:  in addition to common variants of small impact and rare deleterious variants,  there are rare protective gene variants of large impact (below):

LRP5              G171V/+        Extra-strong bones

MSTN             -/-                  Lean muscles                        

SCN9A           -/-                   Insensitivity to pain          

ABCC11        -/-                    Low Odor production   

CCR5, FUT2 -/-                    Virus resistance   

PCSK9           -/-                   Low coronary disease         

APP                A673T/+         Low Alzheimer’s 

GHR, GH       -/-                    Low cancer

SLC30A8       -/+                   Low T2 Diabetes

IFIH1              E627X/+         Low T1 Diabetes

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