Q&A: A Taste Of The Looming Ethical Debate On Gene-Editing Humans

The powerful new gene-editing tool CRISPR is sparking excitement in biology labs — but also calls for a broad discussion about limits, and whether we should ever meddle with the human gene pool. I asked Boston University bio-ethicist Prof. George Annas for his take. Our conversation, edited:

CG: So scientists are saying we should start talking about using CRISPR to alter the human gene pool. What would a conversation like that even sound like?

GA: The conversation is not about CRISPR per se. It’s about: Now that we have techniques to edit the human genome, should we edit the human genome, and if so, for what purposes?

We’ve had this conversation around cloning in the mid-1990s. Most but not all scientists, and almost everyone in the public, agreed we should not try to clone a human being, use our genetic knowledge to make a genetic duplicate human being. And we’ve had very good luck: it’s turned out not to be possible to clone a human being. At least, we don’t know how to do it yet.

But with CRISPR, it seems much more likely that sometime in the not-too-distant future — though it may be decades, this gene editing technology will be dependable enough that someone is likely to try to use it on a human embryo.

This will be a big and dangerous step—dangerous for sure to the resulting child. Many people have no trouble with using genome editing on animals and plants, so long as you’re not harming the animal in a way that makes it suffer. But children do suffer. So the first question is: Should we ever try to edit the genomes of human embryos that are destined to become children? I think the answer is no.

I agree with the scientists who say that it’s definitely not safe to do it now because we can’t predict what other things CRISPR will do to the rest of the genome. We know very little about the genome, and what impact taking out one or a series of base pairs — with CRISPR, you can take a series out — is going to do to the rest of the genome, and hence to the whole organism as it develops.

And the problem with germ-line genetic engineering at the level of the embryo --

— Making genetic changes that will be passed on forever —

Potentially, yes. First they will be passed on to this baby, and this baby will become an adult. And if this “engineered” baby has children, the new traits will be passed on to the next generation, and so on.

So an initial question — and scientists agree with this — is, how many generations do you need to prove that a particular method of genome editing is safe? I would guess most scientists would say, at least four or five. Well, we can do four or five generations in zebrafish or in rats or in fruit flies pretty quickly.. In humans, however, it’s going to take you probably 100 years. So, how many children would you want to follow, and their offspring, for 100 years before you are ready to conclude that editing the human genome is safe for children?

That strikes me as a question that we can’t answer. Because we cannot prove it safe without putting human children at terrible risk of harm, we can’t subject any human child to this experiment. That’s because children can’t consent, and their consent is necessary as a matter of ethics because there are good reasons to anticipate that something will go horribly wrong.

And more broadly, there are potential implications for the whole human race, if we start engineering evolution — ?

I would take the strong position that until we get some mechanism by which the human species can be represented, no one should be permitted to do any experiment that is potentially species-endangering, that could put the entire species at risk of serious damage or even extinction.

I think if genome editing ‘works’ and you can actually produce — and to simplify the discussiion I’ll use the old eugenics terms – “designer” babies that are better babies, smarter babies, stronger babies, babies that would be significantly different from the run-of-the-mill babies — then, I would argue, and some people think this is a little far out — that one of two things will happen:

Either we’ll be horrified at these new humans or super-humans or sub-humans and kill them preemptively before they kill us, or they will become so superior they’ll take over the world and either enslave or kill us.

In either event, we’ll have two types of humans — one of which will be seen as sub-human by the other one — and this will promote what I call “genetic genocide”, one group killing the other based on a perception that the other is subhuman or super-human. If there is any reasonable risk of this happening (1% over the next 3 centuries?) then I believe no one has the moral warrant to put the human species in such a risky position, in the position of creating potential species suicide.

So then we just shouldn’t do it...

Certainly not now. Ultimately, what this comes down to — and scientists understand this argument — is, who has the burden of proof? Do the people who want to use this technique have the burden of proof that it’s safe, or, more likely, not safe? Or do people who want to prevent the use of this technique on human embryos, on children, do they have the burden to prove that it’s dangerous in order to outlaw this use?

Right now, because we don’t have a lot of data, whoever has the burden of proof loses.
Proponents can’t prove it’s safe — they don’t know how to do that. And opponents can’t prove it’s dangerous (although from the Chinese experiments, it can be concluded that the techniques they used are dangerous). But mostly we’re currently in the same position we were in with human cloning: little data and lots of talk.

It does seem like, given how young and still imperfect this technology is, maybe these calls for prudence and caution may be a bit premature...

They may well be. It could turn out that none of this is going to work; it could be like cloning. We imagined, for example, an army of clones to be turned into workers or fighters, some pretty horrible scenarios, but mostly what people imagined was that cloning would be the entrance to germ-line genetic engineering. That was the real problem. It would make genetic engineering easier to do by creating multiple identical embryos to work with. Nobody really wanted to simply duplicate existing humans — they wanted to make a better human. Just as most parents want their children to have better lives than they have had; parents want a “better baby.”

The Chinese have a goal of being the worldwide leaders in genomics in the coming century — so it’s not clear to me, even if we have a ban or moratorium on genome editing, that some Chinese researcher, and the Chinese have already done the experiment on non-viable embryos, wouldn’t do it on viable embryos.

So then, even more, you need a world body to say, ‘You can’t do this.’

You do need a global governing or regulatory body — or at least, a world consensus. We actually already have 40 countries that have outlawed germ-line genetic engineering, legislation that was mostly passed in the context of the cloning debate.

What I argued during the cloning debate, and the argument has equal force in the genome editing debate, is that it is perfectly appropriate to use CRISPR to make medicine, but it should not be used to make babies. At least we should draw that line for now. I do believe you should be able to do research on embryos, but you shouldn’t be able to implant them in a uterus (real or artificial) and have them grow up into a baby, because that’s a child — and (as I’ve already said) you shouldn’t be doing research on children, certainly not at this point and maybe ever.

As a matter of ethics, you always do research first on someone who can consent to it for themselves, someone who can understand the risks and potential benefits and voluntarily agrees to undertake it. That’s never going to be the case for a child or human embryo. So we should never get them involved at all — or not until very late in the game.

The undeniably appealing thing is, though, mightn’t there be families with terrible genetic diseases who could eradicate those diseases by fixing their own genes?

The answer to that is yes, but there are many other ways to do it, such as through donor egg, donor sperm, and adoption.

True, but the other appealing aspect I see — and yes, this is far out and science fiction — is that given the record of humanity, tinkering with our gene pool to make us better might not be a bad thing. What if we could be smarter, less aggressive, less evil? I know that presupposes a lot of genetic knowledge we don’t have now, but what if it were possible, why not become better?

That begs the question of what’s better. And those characteristics — -- love, honor, compassion, whatever you think of as good — to what extent are they mostly genetic, or are they mostly environmental?

It’s complicated. If nothing else, we’ve learned from the Human Genome Project in the last 20 years that life is really complicated. It’s not just one gene, one protein — genes influence each other in many different ways, ways that we’re barely beginning to understand.

The notion that you can use CRISPR to change one gene or part of a gene and that’s all it’s going to change in the genome — it’s not so simple. Even if you could find a gene — which you can’t — for happiness or joy, your children might get the joy gene and also the homicidal maniac gene. They may go together — you may have a good time killing people.

I certainly agree that humans are not at their pinnacle, and we’re not such a wonderful species. Half the world seems to be spending half its time killing each other. Can we do better than the humans we have now? Yes. Will we do it through genetics? I doubt it, any more than we’ve been able to do it through drugs.

There’s a school of thought that says if science can do it, it will do it. Given how surprisingly well CRISPR has worked so far, if we do get to the point where we can tweak the human genome very nicely, do you think we will?

This is my favorite thing that scientists say, and they say it without thinking twice: ‘You can’t stop us — the technology is not stoppable.’

‘The genie out of bottle — ‘

And they say that in the same breath that they say, ‘We’re going to learn how to control nature.’ And what they’re really saying is, ‘We think we can control nature but we know we can’t control ourselves.’ And that’s why people other than scientists have to say, ‘You’re right, you can’t control yourselves, that has to be someone else’s job. Because the science is now so powerful that its potentially dangerous – its products now include things like nuclear weapons, bacterial and viral weapons. Scientists don’t get to decide if or when these will ever be used on humans. ‘

Scientists can’t be trusted to control themselves, so we need to come up with an effective alternative structure.

Scientists have tried to self-regulate. At Asilomar [a 1975 conference that set guidelines for using recombinant DNA], the scientists decided the structure would be physical containment — a big laboratory, a biosafety 4 lab - and biological containment, whatever recombinant DNA creature escaped from the lab, it was engineered so that it couldn’t live outside the lab.

And that has helped...

Those safeguards are great, for bacteria and viruses. Not so great for people or animals... So we need new structures, new oversight, new transparency. The scientists can’t do it alone.

So there needs to be a new human species regulatory agency?

Yes, I’d call it the human species protection agency.

The HSPA!

I know it sounds strangely utopian (or dystopian) because the world can’ t cooperate on anything.

And I can imagine China would say no...

And China would say no, who are you to tell us what to do? So there’s got to be payoff for being involved in this.

You’d first have to want to create this agency, and right now the will’s not there. Historically it’s taken a tragedy for us to say, ‘Oh, we’ve got to regulate that.’ Something horrible has to happen.

I can imagine the image of a gene-engineered baby...

People did say that about cloning: If the first clone is born terribly deformed, or if something is horribly wrong with the child, that’s the end of human cloning.

The main challenge is to make sure any proposed experiment is public, so people get a chance to comment on it before it’s a fait accompli, before it’s finished.

Well, the CRISPR scientists themselves are saying they want public dialogue...

They are. If you want to be really cynical, you could say they are just doing that to throw us off. ‘Don’t worry, leave us alone, we got this, we’re going to have a conference and all the scientists will get together and decide.‘
No, you’re not going to decide! You don’t get to decide that. Scientists get to decide the ‘can‘ questions but not the ‘should‘ questions, at least not when they are using dangerous technologies.

So what’s your prediction? How will this play out?

Oh, somebody’s going to try to use this gene editing to make a better baby at some point. But hopefully we’ll get saved the same way we were saved on cloning, in that it’s just not going to work.

Embryos are much more complicated than most people give them credit for — you have to go through millions of cell divisions to make a baby. The chances of all of them coming out right after you’ve taken the genome and edited it — even edited it perfectly — are extraordinarily low. What are the odds that if you take a cell and make a radical change in its DNA composition, that things either stay the same or get better? Not high.

That’s in the near future. In the far future, no one can predict 250 ahead, or even 25 years ahead....