CRISPR, human genetic modification, & a needed course correction

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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?

9 Comments


  1. Here’s what I think…I’m just a regular citizen with a strong interest in this topic. Quite literally soaking up any new bit of news on a daily basis. I explain this, because despite being as educated as a typical citizen might be able to be, I don’t have enough information to make a solid judgment call. I have more questions specific to this issue of human application than I do answers.

    On the one hand it seems there’s no stopping it. Even if many nations regulate it, some won’t and the pressure will mount quickly for the hold out nations to join the race. I think to myself, isn’t it just a matter of time?

    For me to take a more informed stance, I have to ask…How close are we to understanding that procedure A will safely result in effect B? Sometimes I get the idea this technology is being held back too much. It’s being made out to be so powerful with paradigm shifting consequences 10X that of penicillin. Then I read this technology is in it’s infancy. What would be bad about engineering smarter humans? More immediately, how do we move forward to save lives sooner rather than later? How can we not? If this technology; using procedure X; is believed to be even likely, capable of eradicating cancer in patient Z who is otherwise going to die, don’t the benefits outweigh the risks?

    Bottom line – I don’t see how the next 10-20 years aren’t going to be messy. We’re going to stumble. I certainly don’t fear anything like a zombie apocalypse coming from this. I surely don’t want anyone to get hurt either, but people have free will.

    Not knowing the details of how powerful this technology truly is now/today, and then weighing that knowledge against the dangers due to the fact that again I don’t know the specifics of those dangers…Well it’s driving this citizen absolutely batty! All I can do is keep watching with the assumption that it really is too soon…I don’t have enough information to make a stand, so for now I side with you for the very same reasons you put forth.


    • Hi Jon,
      So you want more straightforward discussions of potential benefits and risks ranging from practical aspects (e.g. oh, we CRISPR’d the wrong spot) to societal things? Some of that I did in my GMO Sapiens book. It was written for a broad audience and I really tackled things from a common sense point of view throughout much of it. Maybe I should do a post here that is more of what you are asking for and less about the nitty gritty tech details?
      Paul


      • Given the implications of this technology, I can’t understand why it doesn’t have it’s own weekly prime time news update hour. Yes, all that you said and more…As an example I want to understand the details of why CRISPR-CAS9 misses it’s target, what we are doing to understand how to improve it, what negative consequences occur…Yes all the nitty-gritty stuff. I can find discussions on topics like this, but at that level of detail it’s often a professor talking to a grad class and so the meanings are lost in technical language.

        I will get my hands on your book. Maybe that will help. You are currently my main resource for information. I check in on Aubrey De Grey, William what’s his name, Doudna, and Elizabeth Parrish, but there’s nothing new coming from them. I’m not finding anything about what they are specifically doing or what the outcomes of their work is. I can’t thank you enough for this forum which gives me a voice and a place to look for answers.


  2. I agree the often cited talking point of inclusive public engagement and outreach on this issue and others is lacking. IMO for a science led public education campaign to be effective it must be undertaken with objective purpose and assigned resources through committed public & private initiatives beyond safe haven boarders & well read circles. Importantly for this debate to resonate with clarity an actively mediated agenda should be prioritized via mainstream media on the perinent issues surrounding the advancing science of the day.

    Jon’s comment above speaks to the need to fill this void.

    Cheers


    • @msemporda,
      Yeah, this is a good point. The thing is, who is going to pay for (as you mention resources) and actually do the educational outreach? I’ve tried in various ways via my book, my TED talk, blogging, speaking at meetings, but a bigger education campaign is needed. Such an initiative could have major beneficial impact. What would the “objective purpose” be? In other words, what’s the agenda and how can it be successfully completed?
      Thanks, Paul


      • I suppose public demand, or should I say the lack of public demand, to know more about what is going on in this field reflects why more outreach isn’t taking place. I wonder what would happen if people knew what this could mean with regard to easing the financial burden from the coming “white tsunami”. I personally find our current medical knowledge to be deplorable. One often goes to the doctor just to hand over a bunch of money and gets nothing in return or worse, gets an addiction to a prescription. That needs to change and this could be a big part of the answer to that problem as well.

        To answer your question I must ask you a few more first…Is this technology close to ready? Is it ready and we are just taking a stance of inaction based on fear? Does it have the power to do the spectacular things we are being told it will be able to? How we one step away from beating this or that cancer? If not, whom is doing what to conquer each problem? Where are the updates? (Other than here, of course).

        Regardless, I think a good place to start is to allow the power and potential of the technology to speak for itself. However, a huge part of the population lacks the experience of a rigorous education to appreciate what’s going on. Even those who do possess the ability to appreciate it don’t seem to believe it. Just listen to an open question-answer forum of Aubrey De Grey to understand that point. My main point is that any main objective needs to be backed up with real, concrete evidence for the public to take notice. To get their attention so to speak.

        That sets the scene for a chicken versus egg dilemma. This to me is reason for some human testing to occur sooner than later. Like Elizabeth Parrish says, begin with; I’m not going to word this correctly; those who have nothing to lose.

        Having said that, I completely recognize I haven’t the experience or expertise to validly convince anyone who does. But then that’s why I’m here talking to you Paul. This brings me back to the idea that if I am one who makes an effort learn about it and I don’t have any idea what I’m talking about, well… where do we start?

        Paul, you pointed out there are things happening now which will tend to have the effect of opening more doors to more risky experiments. Are we on the precipice of a flood of amazing breakthroughs mixed with terrible tragedies that hindsight we will say we should have been able to avoid? Must we take some risk for some reward? Or should I just zip my lip and accept that it’s too soon to know? I fear we haven’t the time.


  3. The practical issue of coming together as a community through leadership initiatives is challenging in itself – however, I would hazard a guess that there are a number of KOLs, institutions and industry associations that would be interested in getting involved in dedicated campaigns (many of whom are already doing scicomm – as you are – even some have specifically indicated a desire to champion public outreach, such as NAS/NAM, during the ongoing gene editing science review process). Resources need to be found from traditional funders and through alternative means around specific initiatives and media centric projects (there are ways). Voices have to be assembled and ongoing participation developed as part of the programming…

    The benefit of establishing such a direct mainstream approach to science communication is immeasurable but cannot be achieved without a willingness to present all perspectives and fully debate the issues openly without recourse. Continuing to ignore there exists an accelerating deficit in understanding the basic science and its societal implications is ill advised. Moreover, there’s an even greater risk due to the misunderstanding fostered by a multitude of inadequate channels.

    The objective purpose is fundamentally associated with reaching the general public. Broadcast or device TV being the most powerful tool in an array of possible media routes. An agenda that is grounded in information transfer through dialogue where scientific issues are presented in layman’s terms throughout, even while discussing technical details. Ultimately the connections to a widening audience will go some way to reversing the knowledge gap and perhaps, if successfully implemented with real engagement as a priority, become destinations for all things cellular & genetic as the science advances.

    Community concern is rightly justified given the ebb and flow of political winds. However, at the moment the public is very confused and the opportunity exists now to move forward in the direction so many have suggested.

    Cheers


  4. I’ll give this all more thought, you guys. At least one place to start is more concrete practical post or posts on key issues avoiding jargon, etc.
    Paul


  5. Hi Paul, I agree with the need for caution with human germline genetic modification. However I would slightly disgree with the following statement you made:

    “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.”

    Genetic sequencing technologies have indeed grown by leaps and bounds in recent times, but genetic screening doesn’t cure a disease, or even completely prevent it despite prophylactic interventions. Surely genetic modification for eradication of such disorders is not “a very illogical proposition”? I do agree that it shouldn’t be attempted at the present time. Not only do we need more dialogue with a broader audience about policy, but there are still gaps in our knowledge about the role of every gene and noncoding region of the genome. Plus the CRISPR technology is still pretty new and there are still studies being done on potential off-target effects.

    Please feel free to correct me if I said something incorrect or if I misunderstood.

    Thanks.
    Jay

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