Moscow biologist and DNA specialist Denis Rebrikov has spent much of the past year kicking a scientific and ethical hornet’s nest with increasing urgency.
In the summer, he announced his ambitions to genetically modify human embryos for pregnancy using a technique nicknamed CRISPR. Then, this month, he said he’d begun lab edits on human eggs with the ultimate aim of clipping out a mutation that can cause deafness.
Rebrikov has assured the world that he won’t go further — for instance, implanting gene-edited eggs for possible pregnancy – unless he has permission from Russian authorities.
And the Russian Health Ministry took the extraordinary step this month of declaring that it’s too soon to make gene-edited babies.
This all comes less than a year after Chinese scientist He Jiankui supercharged global debate over tinkering with the human genome by announcing the birth of twin genetically edited girls, nicknamed Lulu and Nana.
The stunning leap by He into what critics liken to eugenics drew condemnation around the world and banishment by Chinese officials.
Questions revolve around more than just technology and know-how.
RFE/RL talked to three prominent experts about the ethical implications of Rebrikov’s activities and the emerging challenge to humankind that is posed by technology that can forever change the human genetic code.
A Good Place To Start
The World Health Organization (WHO) and scientists from around the world responded to the birth of the Chinese twins with calls for restraint as experts scramble to establish red lines with new technologies that open the door to changing human DNA in the laboratory.
Francoise Baylis, research professor at Dalhousie University in Nova Scotia and author of the book Altered Inheritance: CRISPR And The Ethics Of Human Genome Editing:
Two questions are front and center in discussions and debates on the ethics and governance of heritable human genome editing. The first question focuses on the “whether” of heritable human genome editing. The second question focuses on the “how” of heritable human genome editing. These questions need to be addressed in order because the “how” question need only be addressed if the “whether” question is answered in the affirmative.
“Whether” to proceed with heritable genome editing is not a simple question given the multicultural context in which the question is being asked. Different individuals, organizations, and countries have different goals and objectives.
I have the impression that some are pleased that Dr. He has “crossed the Rubicon” insofar as he has made it easier for others to follow in his footsteps while arguing that they can do well what Dr. He did poorly.
For some, this is the beginning of normalizing the idea that it is not only possible but laudable to pursue heritable human genome editing, and that the main problem with Dr. He’s efforts is that he was premature in moving forward because evidence of safety and efficacy was lacking.
I am always keen to point out that something could be safe and effective and still wrong. Ethics cannot be reduced to the science of safety and efficacy. This is a necessary but by no means a sufficient condition for ethical research involving humans.
Jackie Leach Scully, professor of bioethics and director of the Disability Innovation Institute, University of New South Wales:
There’s no single greatest challenge. Currently, we don’t know how well genome editing works overall. Its safety has not been established, and no country has yet undertaken the kind of broad public discussion that’s needed even to approach a consensus. At the moment, a lot of the taken-for-granted rules of ethics in human research are being questioned. And this, of course, makes it harder to get universal agreement on risks and protections.
In practice, the ethical line is between the manipulation of either egg or embryo, and the use of the manipulated egg or embryo in pregnancy. The first would be just experimental gene editing, and that does raise the question of the legitimacy of using human embryos in research, and whether it’s more permissible to work on eggs (which some people consider are not “proto-humans” if they aren’t yet fertilized) than on embryos (which in principle have the potential to develop into humans). But in my opinion, this is not nearly as serious a question as whether or not it’s ethically legitimate to manipulate a human genome with the intention of allowing that to develop into a person. As far as I can see, that [latter] has always been Dr. Rebrikov’s aim.
Ewa Bartnik, professor of genetics at the University of Warsaw and a member of the WHO expert advisory committee on developing global standards for governance and oversight of human genome editing:
I think if in the future anything is to come of this type of work, an egg is not enough. It has different properties from an embryo. A lot of things happen after fertilization. And an egg is something to start with, and if you are thinking in any way in the future — hopefully a distant one — to do something to modify humans, then you have to work on embryos.
Of course, how you define a human being depends on how you view the world. If you’re a Catholic: Once fertilized, it’s a human being. If you’re anything else, it depends. But if you conduct experiments and then you try to have someone born who is the result of these experiments, it’s incredibly unethical, whatever your viewpoint is.
The Rush To Break New Ground
Rebrikov has a growing list of colorful responses challenging a go-slow approach. “Where did you see the researcher willing to slow down?” he has said. He invoked Lenin to say, “Yesterday was too early, tomorrow will be too late.”
Scully: There are huge systemic pressures on researchers to be the “first” to make particular breakthroughs, and a lot of competitive egos at play as well. The egos may be kept under control in countries with long-established regulatory frameworks, but not in countries whose approach is … more relaxed. When I teach research ethics to young graduate students and postgraduates, I’m always surprised how few of them understand the background to the kind of research ethics and governance frameworks that we have — that they are there for protection (of participants, patients, researchers, society in general) and not just to get in the way of scientists wanting to pursue their work.
I think it’s therefore even possible for a researcher to “go rogue” without even realizing what they are doing. But clearly this isn’t the case with Rebrikov, however, who appears to be pretty dismissive of ethical or regulatory control overall.
Bartnik: The thing is, if you have a person who wants to do something and has the know-how and the money, how do you stop him if he doesn’t do it openly? What countries can do is make regulations. But how do you enforce them? You can stop it if they announce it, like He did. But if He hadn’t announced it, how would you know about it? He [Jiankui] probably had a team of around 20 people. And no one has ever heard anything about blaming anyone else but him.
Baylis: I am not sure that it advances the conversation to focus on so-called “rogue” scientists. There is a context in which scientists doing frontier science are simply doing what they have been trained to do, which is to push the envelope in pursuit of new knowledge. That is how you get a Nobel Prize. There are no awards for being second. There is not even much in the way of acknowledgement of the fact that science is very much a team endeavor, with many standing on the shoulders of many.
It has been reported that Dr. Rebrikov has a high tolerance for risk. The issue here, however, is not what personal risks Dr. Rebrikov is willing to assume but rather what risks society should allow him to visit on others — the women research participants, the prospective parents, the children born, society, etc.
Dr. Rebrikov is reported to have said, “I am doing research at the speed that natural biological factors allow.” This points to an important potential difference between what “can” be done and what “should” be done.
The Challenge Of Russia
A recent report suggested top Russian geneticists and health officials gathered for a “secret” meeting on regulating genetic modification of humans. Another report downplayed its alleged secrecy. Then the Russian Health Ministry assuaged some concerns by saying it agreed with the WHO’s cautious approach.
Bartnik: [Russian Health Ministry officials] appear to be supporting [the WHO position], and I think Russia does not want to have a rogue status — as a country which allows things which everyone else would not accept. So I’m confident that they don’t want this to happen unless there is some kind of a consensus allowing people to go forward with more experimental work, which won’t be for a while, I’m sure.
I don’t have much contact with them. But this is a postcommunist country and they have very strict regulations, and, I think, methods of enforcing them — probably better than many other countries. So I think if they say they do not want to go against the WHO regulations, I think they don’t want to go against WHO regulations [and] that’s that.
They could have ignored [it] and pretended nothing was happening. But they went out of their way to say that they were not for doing weird experiments in their country. And that’s nice. I appreciate it.
Baylis: I think it is very important that the Russian Ministry of Health has made clear statements in support of the WHO position. This demonstrates an interest in working with other nation states to find “common cause.” I think it also demonstrates a clear interest in supporting careful reflection on potential innovation, not unthinking pursuit of science for the sake of science. Rebrikov has said that he will not proceed without regulatory approval, and so the statements by the Ministry of Health are important signals.
Fears Of A Global Rogue Scientists’ Gallery
Rebrikov suggested to RFE/RL in June that with “hundreds” of other researchers around the world using the same CRISPR technique, “maybe in a year” there will be a second scientist “like He.”
Scully: The relative ease of CRISPR technology means there are many places in the world where this could be happening, [and it is] much harder to get an idea of where or how often. I think it would be impossible for a single researcher to do so in complete secrecy. A lot of other people are necessarily involved. This in turn implies either that officialdom gives tacit approval, or the governance structure is so weak that approval is irrelevant. In the latter case, there is all the more reason for some form of international regulation and, ideally, monitoring of compliance.
Voluntary agreements, of course, always leave open the possibility of people just ignoring them or ignoring any moratorium that might be called in the future. But I don’t feel that necessarily means voluntary regulation is pointless or doomed to failure. In other contexts, there are international standards and agreements that are widely respected, even though no one has any power to enforce them. What can also be done is to remove or minimize the incentives (notoriety, money, etc.) to break the agreements.
Bartnik: I think society generally sees us as crazy people running about and doing their stupid experiments, and the movies sort of reinforce that. Scientists are generally — we used to be a kind of authority for many things; now we’re not anymore. I don’t think most scientists are people who like breaking rules in the sense of breaking the law. I cannot exclude that some people might be doing those experiments; I’d say most scientists definitely aren’t. Because we rather like to feel, well, not necessarily comfortable with what we’re doing but we don’t really like breaking the law in most cases.
WHO’s In The Driver’s Seat
The World Health Organization’s (WHO) expert advisory committee on governance and human genome editing issued a statement in May saying that “it would be irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing.” It urged regulatory or ethics authorities to “refrain from issuing approvals for clinical applications for work that involves human germline genome editing.” The WHO committee, meanwhile, continues its work to produce global guidelines.
Scully: In my opinion, [WHO efforts are] very [urgent] — if only to have something to start working with and to critique. For example, if important perspectives have not been given proper weight, that probably won’t become apparent until people can respond to something concrete and start saying, “My point of view, my reasoning, isn’t reflected in these.”
Baylis: I worry about the evident hubris on the part of those who act as if it is reasonable for a small group of elite scientists to direct our human future. With human genome-editing technology we are on the cusp of taking over the human evolutionary story. In my new book Altered Inheritance, I defend the notion of slow science. I argue that the human genome belongs to all of us and we should all have a say in whether it should be intentionally modified. I champion the idea of broad societal consensus with a focus on unity (not unanimity). The goal is for us to find “common cause” and to promote the “common good.” This is a challenging objective that requires time and attention.
Media reports suggest that Dr. Rebrikov is frustrated by the pace of public discussion and debate, and current international efforts at governance. Other like-minded individuals have been known to complain that science is outpacing ethics. I encourage people to deconstruct this claim. What could it possibly mean to say that science is outpacing ethics other than to suggest that science is racing ahead and ethics is lagging behind if it is not actively championing science? On this point I would remind people that ethics is not a handmaiden to science.
Moreover, what matters is not scientific consensus, but societal consensus.
Legitimate And Illegitimate Targets
Rebrikov is trying to snip out a gene that can cause deafness. Even if it works, who is to say that a condition is sufficiently “serious” and merits elimination through such radical means?
Scully: That’s a serious concern in this case, and more generally in other places as well. It’s not just a problem with Russia or China. Even in Europe and the United States there is considerable variation, between and within countries, over whether particular conditions make it impossible to live a good and happy life. There would probably be almost universal agreement about some very severe conditions, but others — classically, these include deafness and short stature — are much more controversial.
It could be argued that, if there is a strong cultural consensus within one country that a condition is serious enough to warrant gene editing, then international debate is irrelevant, i.e. what matters is that regulation reflects that country’s values. However, I’m not convinced that, in the case of Russia, there really is this universal agreement in Russia about the “seriousness” of deafness. I also think it’s legitimate to probe and ask how much of the opinion is an entrenched cultural difference, and how much reflects — for example, the absence of a flourishing signing deaf community in Russia.
A more useful discussion might be around what we — and different countries — actually mean by “having a good life” or “flourishing” overall, rather than spending time on arguing about whether particular conditions are incompatible with having a good life.
Baylis: The focus on deafness is deeply problematic. It should be obvious to most everyone that this is not a “serious” illness/disease and further, as the deaf community reminds us all, this condition ought not to be described as an illness/disease. There is an evident problem with the eugenic goal of trying to eliminate the deaf community in pursuit of some version of “perfection.” Looking at humans to identify and correct imperfection is a deeply problematic way of looking at the world.