May 31, 2020

The Niche

Knoepfler lab stem cell blog

CRISPR, human genetic modification, & a needed course correction

Are designer babies made using CRISPR or other genetic modification technologies closer to reality today? If so, what exactly should we do about it?

Researchers can use CRISPR to genetically modify just about any organism or its cells, but targeting humans is the subject of the most intense discussion including using CRISPR in the human germline for heritable “editing” or genetic modification of humans. This could in theory be done via human embryos or human germ cells with mostly existing technology.cover GMO Sapiens

CRISPR studies on healthy human embryos are apparently now being conducted in the UK and Sweden by Kathy Niakan and Frederick Lanner and potentially others (see here and here) strictly for research (not reproduction).

I support the use of CRISPR for early human embryo research, but it needs to be done carefully and with proper bioethical oversight as well as transparency. To my knowledge to date, no team working on CRISPR in health human embryos has been willing to even say what genes they are targeting so that’s a problem in my view. I would guess at least one group is aiming to knock out key pluripotency genes such as OCT4 and NANOG in otherwise normal human embryos. Will we learn dramatically more about human early embryo development that is distinct from findings in mouse embryos on the same genes? I hope so, but you never know.

We also need to realize that the moment one of these studies on intentional genetic modification of healthy human embryos is published there is a good chance there will be a political firestorm in response from some quarters. This is in part why seemingly pro-heritable human modification arguments popping up need to be responded to and discussed as even the strictly research-focused CRISPR work in healthy human embryos will lead to invocations of germline human modification.

Practically speaking there’s the thorny issue that someone could take relatively easily try to make designer babies. Using the same kind of approach being employed right now to CRISPR healthy human embryos for research, instead one could relatively simply implant them in a surrogate mother working with a fertility clinic to try to make a baby. It wouldn’t be hard to try to do this, but to successfully and safely make a genetically modified human would be extremely difficult or impossible.

That’s just technically speaking. What about societal and family implications? I discuss all of this in my TED talk (below).

In just the past month or so we’ve seen more pro-human germline modification pushes of the kind that I discussed in my book GMO Sapiens, which was focused on use of CRISPR in humans. The topic of human modification is on people’s minds. At two different meetings that I spoke at in the last 12 months, different people have come up to me after the talk to in both cases tell me that they heard that for a price a couple can already get a batch of CRISPR’d human embryos for reproductive purposes in China. I doubt that, but this clearly a notion floating around out there.

The idea of so-called “3-person IVF” (aka “3-parent babies” or mitochondrial transfer or DNA transfer) is now being promoted in a for-profit fashion as an approach to infertility. Others are focused on using this technology to try to prevent mitochondrial disease. Either way it would be a form of human genetic modification even if that isn’t the specific intent, which hasn’t gotten enough discussion.

Nature Biotechnology also just recently published an opinion piece with a title seemingly arguing the issue of human germline modification may be mostly out of our control at this point in terms of policy. It was entitled, “The illusion of control in germline-engineering policy” by Harald König. I myself have wondered if CRISPR germline use in humans is inevitable, but such hypothetical one time use or even a few isolated instances, should they occur, would not mean we should give up on making wise policies. König’s article is more nuanced than its title suggests as this one key passage illustrates:

‘Illusion-of-control’-like notions of universal ethics and bans on germline applications may thus favor one-dimensional thinking and illusionary policies, harboring the danger of leaving aside potentially more realistic and efficient policy alternatives. The latter type of ‘polycentric’ approach should be better capable of exploring the opportunities of genome-editing techniques, foster collaboration between countries and enhance the chances to grasp the broad range of possible ethical and social issues that would have to be taken into account by efficient and trust-building policies.”

An odd New Scientist piece was more directly on the pro-modification bandwagon in terms of tone, claiming to link overall health and intelligence genetically. Some language there also seemed to be promoting genetic “enhancement” including for intelligence:

“One implication is that using gene editing to fix the hundreds of mutations that slightly damage people’s health would make them smarter as well as healthier. “I think this strengthens the moral case for pursuing genome editing technologies,” says ethicist Christopher Gyngell of the University of Oxford. “It would be killing two birds with one stone, and that would be a good thing.”

Gyngell sure sounds in favor of trying for designer babies including for supposedly enhanced intelligence, which is likely an ephemeral goal at best and at worst, something more ominous Those of us with concerns about such ideas need a voice and a plan. Is it enough to just say “human germline modification is off the table” and hope for the best or to state that “human gene editing would be imprudent to try at this time”? The National Academies of various countries including the U.S. and other equivalents have had meetings, issued reports (some of them quite excellent), and now, not much more is being said from the science community about the need for caution.

It’s too quiet on this side.

Why do I care about this enough to risk speaking out?Doudna CRISPR Book

One reason is that I’m convinced that CRISPR is a positive booster rocket for innovative research so potential coming media storms over its use in the human germline could seriously harm non-controversial but transformative CRISPR research. I also believe that use of CRISPR or other technologies in the human germline poses a profound threat to society on a number of levels that equals or more likely greatly outweighs the potential practical health-related benefits of such heritable use, particularly since powerful genetic screening approaches already widely in use make the idea of using CRISPR in the human germline for prevention of genetic disease a very illogical proposition at present.

I just cracked open the new book on CRISPR by Jennifer Doudna and Samuel Sternberg, “A Crack in Creation”. I’m curious to see how much caution they propose in moving forward and how they discuss issues such as human embryos and heritable modification. It is such challenging issues that would invoke part of their subtitle on controlling evolution.

I’m not a very religious person so my arguments in this case are centered on practical risks to our species and to individuals. More democratic and diverse dialogue is needed, contingency plans should be developed for when (not if) additional human germline modification stories pop up using CRISPR or other technologies such as DNA transfer, and I believe that more decisive policies are needed. A lot of good things happened in the past few years in terms of opening up dialogue on the use of CRISPR and other genetic modification-related technologies in humans including in the germline, but this is a marathon not a sprint.

Where do we go from here?

Collectively those of us who have concerns about germline human modification including via CRISPR have been too passive and need a new path or paths from that of the past two years. I favor more assertive policy stances by scientists and scientific bodies, but not actual laws, which are likely to do more harm than good.

What do you think?

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