基因编辑与人类增强的伦理，与朱利安-萨武列斯库（Julian Savulescu）合著

ALEX WOODSON: Welcome to Global Ethics Weekly. I'm Alex Woodson from Carnegie Council in New York City.

This week's podcast is with professor Julian Savulescu. Julian is the Uehiro Chair in Practical Ethics at Oxford University in England and the director of the Oxford Uehiro Centre for Practical Ethics. He is also a visiting professor at Murdoch Children's Research Institute and Melbourne Law School in Australia and the former editor of the Journal of Medical Ethics.

In the third discussion in our gene editing series, Julian and I focused mostly on the ethical questions surrounding this technology, something he was written and spoken about extensively. We discussioned Dr. He Juankui's widely condemned research—something I also talked about in-depth with Dr. Jeffrey Kahn from Johns Hopkins and Dr. Robert Klitzman from Columbia University.

We also touched on human enhancement, how gene editing is perceived differently across world, and some of the frustrations that Julian has with the current level of discourse around these deep ethical issues.

If you’re not familiar with some of the current conversations and controversies around gene editing, I urge you to also listen to my recent podcasts with Robert Klitzman and Jeffrey Kahn.

For now, calling in from Melbourne, Australia, here’s my talk with Julian Savulescu.

Thank you so much for doing this call. I'm looking forward to this talk.

JULIAN SAVULESCU: No problem.

ALEX WOODSON: Just to get started, I saw a talk that you gave in Prague earlier this year. You said when it comes to gene editing you don't think we need new laws, we don't need any new moratoria; you think that the thing that is most necessary is good ethics. What do you mean by "good ethics" when it comes to gene editing, and what are the ethics that you think we need for this technology to be useful?

JULIAN SAVULESCU: First of all, I think you need to have ethics that facilitate good practice. The big picture is, gene editing is an enormously potentially beneficial technology. In the first instance, it's an ultimate cure for genetic disorders; it's actually curing the underlying abnormality. It's also a way of reducing genetic disposition to common diseases like diabetes or heart disease or Alzheimer's disease, and it's a way of enhancing human capacities that contribute to how well our lives go.

The big picture is, we should really be facilitating research into gene editing and not placing unnecessary and unethical obstructions in front of it. That's the first part. I think there is too much negativity about gene editing.

Then you need to draw some lines on how that research and application should proceed. One example that I have given is that it clearly still has some risk of off-target effects, although that is reducing, so at the moment it is a technology that has risks. If you were to attempt the sort of procedure that He Jiankui performed in China in November of last year of gene editing human embryos, you should use embryos which would not otherwise survive so that if there is an off-target mutation, the cost of that to the embryo or the child is far less than if you create cancer in a child with a normal life expectancy.

I think that was an example of failure to understand a basic ethical principle of minimizing expected harm from research. Those sorts of trials could be done but in embryos with catastrophic conditions like Tay-Sachs disease.

Even experts like the dean of Harvard Medical School George Daley or Nobel Laureate David Baltimore, who are supporting this technology, don't get this distinction between simply addressing a medical need, which is research to treat a medical condition, and starting with research which minimizes the expected harms. Daley said, the first trial should either be on Tay-Sachs disease or Huntington's disease.

Huntington's disease is a disease that starts at the age of 40, but those individuals have 40 good years that they stand to lose if the risks of the technology in early childhood materialize, so that's not a candidate for first-in-human trials, whereas Tay-Sachs is. You need to understand some of the basic ethical principles, like ensuring that there is reasonable risk.

Another area that is an example of bad ethics is one where people say that research requires consent. Typically researching competent adults does require and should require consent, but when it comes to research on embryos, embryos can't consent, so this standard of consent is not one that can be applied, and appealing to the parents or the doctors or the courts is really a fudge. What you really need to do there is ensure that the research is safe enough and beneficial enough for a future individual.

I think in some cases we are unnecessarily obstructing. In other cases, we're overly obstructing research. When we do attempt to apply principles they're often in a very sloppy and under-worked-out way.

ALEX WOODSON: You mentioned Dr. He Jiankui and his experiments last year. This is something that I have talked about with Dr. Klitzman and Dr. Jeffrey Kahn. I know you called it "monstrous." I'm sure you chose that word very specifically. You have already gotten into it a little bit, but what about that was particularly monstrous, and how has that really changed the conversations around gene editing over the past year?

JULIAN SAVULESCU: It was a stupid mistake. What's interesting about He Jiankui is that he actually has given ethics lectures and written an article on ethics, which just shows that he doesn't even understand the terms that he's using.

What was monstrous about that experiment was that he took two completely normal embryos with a normal life expectancy and subjected them to the risks of gene editing for the sake of immunity to HIV. You could avoid HIV by not having unprotected intercourse or by avoiding needle exchange or a bunch of other ways. He basically exposed them to risks for no necessary benefit, which is different to a condition like Tay-Sachs disease, where you will necessarily develop the condition, so that the risks could be outweighed by the benefits. To put it simply, the benefits didn't outweigh the risks to those individuals.

What he had already done is he had taken HIV-discordant couples, which means the man had HIV and the woman didn't; in that case, there's a high chance that children will have HIV infected from the father's sperm. But he washed the sperm and also put the father on antiretrovirals to lower the viral load, so there was no risk that the embryo itself would develop the infection from the father. So it didn't need this gene editing in any way.

I think exposing people to significant unnecessary risks is monstrous. That's exactly what the Nazis did; they took healthy people and exposed them to the risks of dying through hypothermia experiments or though infecting them with viruses or through surgical interventions that had no possible benefit for them.

This isn't quite as bad as that because there is some theoretical benefit to being immune to HIV. If there was a vaccine that made us immune to HIV, we would be falling over ourselves to get it, but if the vaccine had a 10 percent or a 1 percent or a 0.5 percent chance of causing cancer, we wouldn't be falling over ourselves to have it. I think he has exposed those two children, Lulu and Nana, to unnecessary and excessive risks.

ALEX WOODSON: Dr. He did this in Shenzhen, in China. I know China has condemned this research just as much as any other government, nation, or agency—whoever is observing it—but there still are big differences in the way China may look at ethics and someone in the United States, Australia, or the United Kingdom may look at ethics. Going back to my first question, do you worry that a place like China, a place like whatever country it may be, with this technology moving across borders, how do you get everyone on the same page as far as the ethics of this new technology?

JULIAN SAVULESCU: Unless you create a global government with an international police force and international laws that are binding, you can't use legal instruments to deal with this effectively. What you need are ethical norms that result in blame and disapprobation, as occurred in the Chinese case. It was ambiguous whether there were actually laws that prevented this in China—there may or may not have been—but the Chinese reaction has been as a result of international disapproval.

I think you have to first of all educate people as to what ethics does require. As I said, I think first-in-human trials of gene editing could be done using catastrophic conditions that kill the embryo in embryonic development or the baby in very early life. You could do this research but do it ethically.

I think you need to first of all have proper ethical education and ethical dissemination, not the superficial kind that He Jiankui had, where he was just able to use the concept in an attempt to defend what he was doing. He Jiankui actually mentioned the case of Jesse Gelsinger, a young man who was 18 and who died in a gene therapy trial in 1999. The problem with Gelsinger again was that they chose to use adults with a mild form of a genetic condition instead of infants with a lethal form. I wrote that that was the ethical mistake of that trail, and he repeated that mistake, despite saying, "We have to learn from the lessons of Gelsinger."

I think until scientists really understand what ethics is, and journals and governments are prepared to back that up, this sort of research will occur somewhere because the prizes are so high. He Jiankui wants to get a Nobel Prize; he wants to be the first person to produce a gene-edited baby.

Let's face it. In vitro fertilization was done in a similar way. People didn't know what the risks were going to be in humans. It turned out to be successful. If it turns out that Lulu and Nana go on to lead healthy lives in the future, He Jiankui may well be getting a Nobel Prize. It just depends on how it turns out in part.

I think we need to embed ethics more in science rather than attempting to create lots of laws that people can break, and if they break them successfully, it will be worth their while. That's the lesson of doping in sports: It's very easy to bypass the doping tests using natural physiological substances like growth hormone or your own blood or erythropoietin, so when the prize is so high and the possibility of detection is low, people will break the laws.

The way to avoid that is to ramp up the punishments, reduce the incentives, and increase the enforcement. In this case, the enforcement has to be through the community, and people knew about this research in the United States and elsewhere and didn't discourage it and didn't direct it into a more ethically acceptable way.

ALEX WOODSON: I want to talk a little bit more about these conversations and how scientists and researchers at different agencies are talking about these issues, but I just want to talk about another ethical concern. This is something that Dr. Klitzman at Columbia University talked about with me—he has written about this as well—which is, is gene editing leading to greater inequality? Is that a concern that you have when you look at this technology?

JULIAN SAVULESCU: It is certainly a major concern because any powerful technology can increase or reduce inequality. Health care, education, and technology can all increase inequality if they're expensive and available through the market and through a capitalist system. So yes, that is a major concern.

It's also important—to try to put this into perspective—that gene-editing technology is not enormously expensive. Editing embryos is not like trying to send somebody to the moon, and compared to the costs of the diseases that it is addressing it's extremely good value for money.

I'll just tell you one example. One genetic disorder, Gaucher disease, costs about $300,000 a year to treat using enzyme-replacement therapy because the gene isn't producing glucoserebrosidase. With one gene edit for a few thousand dollars the body itself will produce that enzyme every day for the rest of that individual's life instead of having to spend in the United Kingdom ₤18 million a year in treating that disorder.

I think it's important not to use these arguments as a rationalization for a more visceral or another different objection to gene editing. Gene-editing technology, when it comes to treating or preventing disease, is just like a genetic form of health care. When it comes to human enhancement, it's just another human-enhancement technology that is probably going to be less powerful than computing and artificial intelligence and the Internet.

We already have very effective health interventions and very effective human-enhancement technologies. Gene editing is not going to change that landscape significantly, at least in the foreseeable future. If you were able to radically modify the human genome, introducing sequences from non-human animals or novel genetic sequences that gave humans unprecedented capacities, that would be a game changer, but at the moment we're struggling to cure cystic fibrosis.

ALEX WOODSON: I know you talk a lot about human enhancement, and you mentioned it in the last answer too. That would be things like improving IQ, or—one thing that I'm very interested in is you spoke somewhere about "moral enhancement," improving empathy with genetic enhancement. I have many questions about this, but how close are we to these types of technologies, where humans can increase their IQ or increase their empathy with gene editing or with other types of technology?

JULIAN SAVULESCU: We're on the cusp of it. To take intelligence, there are now polygenic scores that account for about 50 percent of intelligence, so roughly 50 percent of intelligence is genetic. I think scientists estimate that they will be able to account for 25 percent of intelligence using some current genetic technologies through polygenic risk scores.

There are already companies offering polygenic risk scores for low-normal intelligence in the United States of testing for embryos, where you can test embryos to see which of them are going to be predicted—probabilistically, that is, that have a higher chance—to have a lower-normal IQ. The company says that, "You will be able to use that to predict higher-than-normal IQ." That isn't to say that that child will have a higher IQ, but you're increasing the probability.

China is spending an enormous amount of money looking at the genetics of intelligence. The Beijing Genetics Institute has one of the richest tens of high-throughput DNA sequences that are looking at the genetic contribution to intelligence of world experts like Robert Plomin, and they have done a lot of the research that has contributed to the recent understanding of the polygenic contribution of genes to intelligence.

They're not doing that for fun, they're doing that for enhancement purposes because they realize the potential of even small improvements in human intelligence. DARPA (Defense Advanced Research Projects Agency), the research arm of the U.S. military, said that even a small increase in the IQ of the working population would have the same economic benefits as the introduction of the Internet.

Based on studies of removing lead, which reduces IQ—removing it from paint and petrol—people have estimated that a 3 percent increase in population-level IQ would reduce welfare recipiency by about 20 percent and add 1.5 percent to gross domestic product (GDP). I think the Chinese are clearly pushing forward on understanding the genetic contribution to intelligence because they're not affected by ideological debates about nature versus nurture or other debates about intelligence; they want to see what the results are.

I don't think that this foray into gene editing that occurred in China last year is purely about treating diseases. I don't think that the main goal is to cure HIV in Africa, it's about proving the principle that you can safely gene edit human beings. In fact, it was an enhancement application; it was giving two normal embryos a capacity that they wouldn't otherwise have had. It's only a short step from there to editing them to be more intelligent than they would have been.

I think the main goals of the gene-editing project really are going to be delaying aging and increasing health span so we're not spending a large fraction of our GDP on treating degenerative diseases of old age and enhancing normal human capacities like intelligence.

Then, people will have an interest in what sort of citizens or what sort of people we are, how altruistic we are, or—in China's case, maybe how obedient people are. There will be some genetic contribution to those sorts of traits that are capable of being modified.

In all these cases you're not determining the outcome, but you're changing the balance of probabilities. I think there's no doubt that by modifying people with genes you can change the balance of probabilities for common diseases and you can change the balance of probabilities for talents and personality types.

ALEX WOODSON: I think I'm getting this correctly. You argue that it's unethical not to pursue these types of human enhancements, correct?

JULIAN SAVULESCU: If you take a Darwinian view of the human being, you don't see humans as these sorts of fine specimens, all made in the image of God, that are all equal in all respects. We may have prescriptive equality—that is, we all ought to be treated equally—but it's manifestly obvious that people differ in nearly every quality that matters to us.

Just take lifespan. People have different lifespans, and that can all be corrected by managing the environment or the child's upbringing, or some of it can. But hair color, height, intelligence, empathy, aggressiveness, introversion, extraversion, eroticism, and novelty-seeking, all of these properties vary from individual to individual, and they have some genetic contributions. Unless you have the view that somehow there is a master plan to this natural inequality across characteristics—if you reject that view, which I do, then you have to say: "Well, what's the right level of aggressiveness? What's the right level of intelligence?"

For nearly everyone the right level is not going to be the level that nature happens to have given them, and if science gives us the opportunity to change that level either up or down, in my view if the intervention is safe enough, we should make a decision about whether we want to go up or down, up or down in anxiety, up or down in ability to understand or to feel other people's emotions. Genetics and genomics and the "Genetic Revolution" is giving us the opportunity to change those features at the most basic level.

But we are also able to change them through drugs or through environmental manipulations, through school and education. There are probably even moral enhancers that aim at bringing out certain qualities in people and suppressing other qualities, so this idea of moral and cognitive improvement is really a banal and very familiar one. It's just that people seem to think that genetics is somehow different to other biological or social interventions.

But genes just make proteins, and proteins just contribute to functions as do diet and environment. What really matters are our minds and our personalities and our values and our hopes and our desires and our behavior, and genes are just one way of influencing those.

ALEX WOODSON: Last question, to try to tie some of this together: What is your feeling on the types of conversations that you're having, that you're seeing out there in the world, about this technology with scientists, policymakers, philosophers, everyone who is getting involved in these discussions? Do you think things are going in the right direction? Are you frustrated by some things that people are saying or people are thinking? What's the status right now of the ethical overview of this technology at the moment?

JULIAN SAVULESCU: This represents my personal interest and bias into the power base. I think this veneer of discussion on the ethics of it is incredibly superficial, that it isn't really about the ethics; it's about people's emotions and people's power interests.

Scientists have an enormous interest in pushing this technology forward. There are Nobel Prizes at the end of it and huge amounts of money. Governments have an interest in it because it has enormous economic advantages. People have an interest in it because they have tropes of science fiction movies or hopes for their own lives of immortality or better conditions for their children, and you see a power play of different pressures.

A lot of the ethics is either social signaling or this very pedestrian application of, "Let's not repeat what happened with the Nazis" and apply very simplistic ideas of human rights. There isn't really any deep discussion about the meaning of life and the sorts of qualities that we want the next generation of human beings to have: How much sacrifice of individuals for the sake of society is justifiable, or how much risk to society is justifiable to enable individuals to have either freedom or well-being? None of the deep ethical questions are being addressed. It's all about, "Wow! We need a moratorium."

But what are we going to do at the end of the moratorium? The same questions will still be there, and we will still be avoiding them in the same way. I don't have much hope for that. I think the prospects for deep, meaningful, ethical discourse and progress is extraordinarily limited after my 25–30 years in the field.

I think what will happen is someone will gene edit successfully, and it will have benefits. There will be a market for it, people will make a lot of money out of it, and we will engineer new preferences in people for certain sorts of gene edits, and there will be more money made for it, and we won't necessarily progress in a direction that either promotes people's freedom or promotes their well-being. We don't even have a concept of well-being that is clearly guiding these debates. We don't even know what would be good for people beyond preventing disease; we have vague ideas.

I think the first place we should be starting at is trying to understand what is good for people: What makes a good life, and how do genes contribute to that? What is a good society, and how do genes contribute to that? What should be the limits of the pursuit of that?

But those aren't really the central questions. It's really about, "This would involve a heritable change, so we shouldn't be doing it." Smoking causes heritable change. The sun causes heritable changes. Having children when you're old causes heritable change. That's not a significant moral issue.

The issue is really about the risks and benefits, and what value is, and today we have this I think terrible situation where people are relativists. They think that value is just in the eye of the beholder, that whatever you identify with is a value. If that's the case, it's just chaos and disintegration of society because there are no unifying values. I think those are the sorts of discussions that we need to have, but we seem to be going in precisely the opposite direction.

ALEX WOODSON: I know you have to get going, but just really quickly, what can we do to put this into a more positive direction?

JULIAN SAVULESCU: When I don't have to get more grants and produce more peer-reviewed publications, I want to try to focus on the education of young people and children. I think there's not that much hope now. I think people are too ossified in their characters and their ethical outlook. I think the hope is education of the next generation in ethics, but proper ethics, not the sort of stuff they currently get taught.

I think the only chance is to become more open, able to identify ethical issues and think more analytically and logically through them, and to develop value commitments. I think one of the biggest challenges is we don't have—now with the fall of Christian and religious values, at least for Western societies—the sole governing values informing social development.

I think we need to reinvent a set of secular moral values that will govern all our institutions, not just for gene-editing research, but we seem to be moving away from this idea that society can have values that people sign up to. Value now is in the eye of the beholder.

ALEX WOODSON: Thank you very much for your time. I'm really happy we had this conversation.