A conversation with George Church on Genomics & Germline Human Genetic Modification

George ChurchI 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 interview.

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

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

17 thoughts on “A conversation with George Church on Genomics & Germline Human Genetic Modification

  1. I am not certain that I would necessarily view a gene variant that renders one insensitive to pain as protective. Such people may be much more likely to injure themselves without noticing, something that I would view as undesirable.

  2. What do you think, when will it be possible to heal disorders by changing genes in adults? I heard there have already happen first trials.

  3. Many people think the stem cells will change our medicine completely, but others think the gene therapies will be much more sucessful in the future. What do you think?

    • While both are promising, one might argue that combining the two together could yield the most powerful impact in some cases.

  4. George Church puts things into a thoroughly sensible perspective.

    That being said, I’m not one to abandon a word just because many Governments (in this instance it is unfair to just beat up on the USA) have used it as camouflage to abuse human rights and freedoms. The difficulty with “eugenics” has always in the application… and that difficulty remains no matter what the word.

    I am reminded of a book I read some years ago, entitled “Survival of the Sickest”. Here we learn that some of the things that we now call diseases actually exist because they improved the odds for survival in earlier times. Lynn Margulis showed us that sex has its origin in cannibalism and that death is a trade-off for making a body.

    My point is that natural evolution has always involved compromise. I would be surprised if a new era of human-directed evolution didn’t also involve compromises, many unknowable. That’s the way life is, press on. But some humble reflection is required before we pronounce a list of most desirable genes…

    Also, I think that there is actually more to the matter than “safety and efficacy” — especially when when pronouncing “safety and efficacy” is in the hands of governments and their agencies. No, I would say that dignity, education, freedom, and informed debate are far, far more important.

    • @Brian
      Answer From George Church:
      These are not mutually exclusive. To achieve safety and efficacy it helps to have many other cultural norms in place. Yes; these might become decoupled, but I think it more likely that we will keep getting better at all of these. Germline modification is just one of many technologies which need (and indeed get) considerable scrutiny.

  5. “Also, I think that there is actually more to the matter than “safety and efficacy” — especially when when pronouncing “safety and efficacy” is in the hands of governments and their agencies. No, I would say that dignity, education, freedom, and informed debate are far, far more important.”

    I think you need to be careful what you ask for. Someone needs to supervise things to assure safety and efficacy, who would it be besides the government? Only government has the force of law. I am not a fan of big government, but some government is necessary.

    Also it is very easy for informed debate to degenerate into something else, and it is easy for quackery to hide in a discussion that appears to be informed debate. Take a look at today’s post by David Gorski on the Science-Based Medicine blog, and you will see an example of what I am worrying about.

    I did save a PDF of the paper by Novella and Gorski which I will happy to provide anyone who might be interested. It is now behind a paywall.

    • Apparently there is some effort amongst scientists working in this arena for a sort of self-imposed “pause” or even a moratorium on heritable human genetic modification (see Antonio’s piece), but some powerful folks are opposed and some efforts at what could be stepping stones to germline human modifications are still ongoing. Thus, in the real world, it seems that some of the research into human genetic modification will continue to proceed. I don’t see any particular evidence of a governmental body in the US for example that would have the will to act pro-actively to have any major impact. The FDA is likely to be reactive after the fact. In some other countries with weaker regulatory frameworks there is likely to be even less of a chance of delaying heritable human genetic modification. Despite all of this, efforts at discussion and some consensus even in one area (e.g. in the US) could be helpful and have positive impact.

  6. Dear Michael,
    I accept your point. Nevertheless, I think that “dignity, education, freedom, and quality information” keep governments from going totally off the rails.

    I checked out the Gorski blog. Scientifically, I’d totally agree with him. But I’ve come to understand that a more sympathetic approach is required to change minds in the faith-based community.

  7. This is fascinating to read, but I think there are so many aspects that weren’t brought up. To touch on only one of them: who will have access to all these wonderful genetic treatments and tests, and who won’t? Would this trend only sharpen and deepen the inequalities in access to medicine in our society? Would these things actually be affordable for a huge chunk of the population? Will it simply end up depending on great insurance, deep pockets, or both? These are uncomfortable questions which must be asked.

    And I’d love to get a PDF of the Novella and Gorski piece. 🙂

    • @Catherine
      Answer from George Church:
      The cost and distribution of technologies can change swiftly, for example, cell phones, search engines and DNA sequencing. Indeed one of the top priorities of my group has been to bring down various technology costs to nearly zero.

  8. @Michael.
    Answer from George Church:
    I agree — and that applies to every variant on this list (and other lists). Nearly all technologies and evolutionary events involve trade-offs in which new goals trump old ones. For the specific example of pain, this SCN9A variation can inspire us to develop new ways to turn that gene function down temporarily, such that pain might be reduced without resorting to more addictive conventional drugs (opiate pathway). This gene is indeed a new target for pharma research.

  9. By our technical civilisation and medical sciences we practically stopped the natural selection. This means we are devolving (the entropy – the disharmony is growing in human genome) and our devolution will be much faster than our evolution was. Unfortunately we accelerate our devolution. Some references:
    Is the human race evolving or devolving?
    – Are humans devolving? Research suggests humans losing intellectual, emotional abilities
    – Kelly Clancy: Your Brain Is On the Brink of Chaos – Neurological evidence for chaos in the nervous system is growing.
    – Gerald R. Crabtree: Our fragile intellect. Part I
    Trends in Genetics Volume 29, Issue 1, January 2013, Pages 1–3
    – Kevin J. Mitchell: Genetic entropy and the human intellect
    Trends in Genetics Volume 29, Issue 2, February 2013, Pages 59–60
    – Dana Dabelea et al.: Prevalence of Type 1 and Type 2 Diabetes Among Children and Adolescents From 2001 to 2009
    JAMA. 2014;311(17):1778-1786. doi:10.1001/jama.2014.3201.
    If the growing rate of prevalence remains constant we can predict, that in US around 2220 every youth will be affected both diabetes 1 and 2.
    – Rising Mental Health Issues Facing Our Children, in Five Charts
    Percent increase from 2010 to 2013: anxiety + 72 %, autism + 52 %, depression + 47 %, eating disorder + 29 %.
    – Some more: http://www.science20.com/entropy_and_sodium_intakes_wicked_problems_health_sciences-120016
    – To stop our devolution possible only by genetic intervention. This intervention is inevitably necessary before it’s not too late. Without intervention the growing entropy will destroy us and the humanity will die out within 250 years! This is the sad reality, so this debate about embryo editing shows astonishingly narrow minded irresponsibility and is meaningless.

  10. In a discussion, George Church mentioned the use of CRISP for age-reversal.

    The article is here “CRISPR: Genome engineering with a purpose”


    and here is the paragraph:

    “The objective is not to extend death, to extend the worst part of our lives, but to reverse aging. Reversal of aging is much easier to do than longevity,” Church said. “We’re attacking this; my lab and others are looking at full genome sequencing of super-centenarians. It’s probably not their environment that’s making the rule on time, but hopefully rare factors.”

    This is something that caught my attention.

    Do you know anything else on this subject?

    Would be nice if professor George Church will give us more details and good news on reverse aging!

    This is very exciting way of using CRISPR/Cas9 and I hope there will be solid new developments on this soon.


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