Gene Editing: An Interview with Henry T. Greely

Interview by Hart Fogel

The concept of gene editing has long inspired imaginative speculation regarding what the future holds, and continuous advances in the applications of this technology only stimulate more discussion concerning both its benefits and potential ethical problems. To explore the topic further with specific regard to CRISPR-Cas9 gene editing, senior editor Hart Fogel conducted an interview via e-mail with Henry T. Greely, director of the Center for Law and the Biosciences at Stanford Law School. In addition to serving as the chair of California’s Human Stem Cell Research Advisory Committee, Greely is a member of and advisor for numerous organizations and policy efforts dedicated to issues including genetics, stem cell research and neuroscience.

Hart Fogel (HF): Briefly, what is CRISPR-Cas9 gene editing?

Henry Greely (HG): CRISPR (currently most frequently done in conjunction with a protein called Cas9 but it has been, and will be, done with other molecules) is a remarkably fast, accurate, cheap, and easy way to cut DNA in chromosomes in very precise locations. It can also be coupled with methods to insert new DNA sequences into the place where the old bits were cut out, but it is not as precise and accurate in that context.

HF: In many publications and platforms for discussion, CRISPR has been hailed as a revolutionary technology that will have a variety of profound effects on and implications for society. Is the significance of this technology being overstated, or is this truly ground-breaking?

HG: It is truly ground breaking, but in an interesting way. It isn’t the first gene editing method. Arguably, that was invented (at least by humans) over 45 years ago. But it is an order of magnitude … faster, cheaper, easier, and more accurate than earlier versions. It’s like the Model T - not the first car, but the one that changed the world.

HF: How is gene editing transforming current approaches to and conversations about medicine, healthcare and public policy?

HG: CRISPR is being used in an enormous variety of research projects involving humans and a wide variety of non-humans. Right now, that’s it. It isn’t yet being used in any products, though some agriculture products produced by it may come online soon. Similarly, it is being discussed in terms of public policy but little has been done yet. FDA [Food and Drug Administration] has proposed some regulatory changes for [genetically modified] animals; USDA [United States Department of Agriculture] has sought advice about regulatory changes for plants. And Congress has forbidden NIH [National Institutes of Health] to fund any research into modifying humans in ways that pass down to future generations (“germline modification”) as well as forbidding [the] FDA from considering any applications to do so. That’s in an appropriations rider and, in theory, expires soon, but I suspect it will be put into the next appropriations bill or continuing resolution. It is not “about” CRISPR but it is clearly aimed at it.

HF: What are some of the main ethical concerns surrounding CRISPR gene editing?

HG: For humans, the loud one is the designer baby/eugenics/playing God complex. The ones that I think are more intellectually substantial involve safety of the babies so made (first and foremost) but also coercion and equity.

For non-humans, there hasn’t been nearly enough discussion but the biggest concerns are environmental effects though animal welfare and some form of “naturalness” (the anti-GMO [genetically modified organism] concern) are also implicated.

HF: How much opposition has gene editing faced, and who has primarily been raising objections?

HG: See above. So far mainly bioethicists, public intellectuals, and a few religious leaders for the human side. It gets a lot of press and generates concern but I don’t think there’s much grass roots opposition (or support, except from the relevant disease organizations whose members hope it will lead to cures). On the non-human side, environmental ethics folks and the anti-GMO forces, notably Greenpeace.

HF: In the public consciousness, gene editing is often associated with the concept of "designer babies" -- human embryos modified in order to produce babies with specific characteristics. Considering that, as reported, scientists recently used CRISPR to edit viable human embryos for the first time, how plausible is this vision for the future? What potential problems could germline gene editing of embryos to induce heritable mutations pose at both individual and societal levels?

HG: We need at least a decade of safety testing - on human and non-human embryos outside the body and on non-human embryos, fetuses, and offspring, before it would be anything other than criminally reckless to try to make a baby after embryo editing. If it all works, “designer babies” are still scientifically problematic. Genes (and traits) are complicated. We don’t know how to make super babies or X-Men. We don’t know what genetic variations increase intelligence, math ability, sports ability, etc., or what their downsides would be. Plus, for most simple genetic traits (like powerfully genetic diseases), an alternative called Preimplantation Genetic Diagnosis (PGD) will almost always work just as well ... and it has 27 years of clinical experience. I do suspect that, if proven safe, CRISPR (or its successors) will be used in at least a few cases to avoid genetic disease. The bigger fight will be on non-disease traits.

The societal level depends entirely on what uses turn out to be possible and actually adopted. I will only say that I strongly doubt that the very attractive - in an approach/avoidance/horror movie way - dystopian scenarios are at all likely.

HF: How widespread is the use of CRISPR in both laboratory research settings and the private sector?

HG: Extremely. Just about anyone who, for any reason, wants to modify DNA is trying CRISPR. (Private sector, though, is, at this point, almost all research, though commercial research.)

HF: Does the adoption and use of CRISPR gene editing by private companies pose any special risks? Can we expect to see a rise in direct-to-consumer applications of this technology, and if so, what implications would this trend have for consumers and the public at large?

HG: Only if we let it. If we regulate appropriately, neither private companies nor direct-to-consumer should be a problem (though, at least in the human applications, I find direct-to-consumer a little hard to envision). In fact, in our society, if you are going to get (almost) anything into widespread use, you need the private sector.

HF: How should the use of gene editing be regulated to protect people while still encouraging innovation and embracing positive uses of the technology? What rules exist and what rules need to be established?

HG: At the very least there should be very tight safety rules for its use in humans. The FDA already administers those. For non-humans there should be more concern about animal welfare, environmental effects of escape or release into the wild, and plans to “clean up” if an environmental release goes bad. Those are not yet sufficiently regulated.

HF: What else still needs to be studied in order to thoroughly understand the ethical implications of CRISPR?

HG: The ethics of technologies evolve with the technologies and with the cultures in which they are used. Health insurance and genetics isn’t much of a problem in the UK because they have universal health coverage. It could be in the U.S. because we don’t. But in 15 years, we might. I think we should focus on specific kinds of CRISPR uses in [a] specific society and setting - and focus on educating the public about the issues and encouraging public discussion. In the end, science and technologies will go only as far as their societies want them to go. An educated society is likely, I trust, to make better decisions.