“I’m disturbed by mixed monkey-human embryos, but maybe that’s because I don’t know enough” | Science & Tech

Professor Knoppers, born 71 years ago in Hilversum (The Netherlands) and raised in Canada, is an international reference point for the moral dilemmas involved in genetic engineering.
Professor Knoppers, born 71 years ago in Hilversum (The Netherlands) and raised in Canada, is an international reference point for the moral dilemmas involved in genetic engineering.Consuelo Bautista

Just over three years ago, Chinese scientist He Jiankui surprised the world by announcing that the first three genetically modified babies had been born; their genome supposedly edited to make them immune to the AIDS virus. For Professor Bartha Knoppers, a world authority on the ethical aspects of genetics, genomics and biotechnology, the verdict was clear. Jiankui’s intervention was unnecessary and sloppy, deserving of the prison sentence and the almost unanimous contempt of his colleagues that it received. On other occasions, the ethical line is much harder to draw.

She participated in writing the Universal Declaration on the Human Genome and Human Rights, which was adopted by the United Nations in 1998 and prohibits human cloning. More recently, she has been a member of the international commission created after the He Jiankui scandal. The expert group warned that gene editing techniques are still not safe, but left the door open for modifying the genes of children to avoid lethal diseases. Knoppers, director of the Center for Genomics and Policy at McGill University in Montreal (Canada), passed through Barcelona on March 21 to speak at a conference at the Center for Genomic Regulation.

Question: American chemist Jennifer Doudna (the mother of the CRISPR technique, which makes cheaper and relatively accurate gene editing possible) says she has had nightmares in which Adolf Hitler, covered with a pig mask, is asking her for more information about her invention. What nightmares do you have about genome editing?

Answer: I don’t have them. I’m optimistic. Perhaps I am too romantic. But, on the whole, the scientists I have worked with all my life are wonderful and very responsible people. I’m sure there are scientists who have evil intentions, but I have not met them. Sometimes we assume the worst of futures and try to make regulations from that assumption, but this isn’t the way to manage these new technologies – I don’t take the approach that something monstrous is going to happen.

Q. We have the example of the Chinese scientist He Jiankui.

A. There are irresponsible scientists and he is an example, but an irresponsible scientist or two can’t taint all those who are trying to advance medicine.

Q. Are you in favor of editing the human genome in such a way that the changes are inherited by following generations?

A. I was part of the international commission that prepared a report in 2020. We said that “at the moment” there is no safe and effective way to edit the germline (modifications that take place in the eggs, sperm or embryos themselves when they are only a single cell and that are then inherited by subsequent cells). So, at this point, I don’t support any intervention that hasn’t been shown to be safe and effective before it is applied to humans.

Q. Using the CRISPR technique, He Jiankui modified the genome in three babies. Nobody thinks that these children will be the last. How do you think the fourth baby will be “CRISPR-ized” – when, in what country, and for what reason?

A. I don’t think about it. We have so much work to do in supporting responsible science that I don’t want to spend my life predicting what can go wrong and creating collective imaginaries, like the movies. I don’t want to create science fiction about CRISPR because the more you talk about it, the more it seems real. I prefer to be creating regulatory frameworks and laws to ensure that science never enters areas that are harmful to human beings.

Q. The question was positive: if you imagine that the fourth CRISPR-ized baby’s genome is modified to avoid a disease, for example.

A. It could be. We discuss this possibility in our report, but the situations in which a couple would need CRISPR to modify their children’s embryos are extremely rare, so its actual usefulness is extremely low. So why work on it when you could be doing somatic therapies [modification of the genome of an adult],? or developing treatments for rare diseases? I don’t want to always assume the negative in the way I work.

Q. Do you think CRISPR will change the future of humanity?

A. Changing the genetic makeup of the population takes hundreds and hundreds of years. I don’t think the birth of a quote-unquote “successful baby” using CRISPR technology will affect humanity. We’re already mutating, so one more mutation… I think we need to reflect on it, I’m not saying ignore it, but let’s not set our frameworks based on the worst case scenario, like, “There should be a law against this ” or other such instinctive reactions. We need a big public discussion, one that is not always based on the weird things that can happen.

Q. Do you have any red lines on genome editing?

A. I would put a red line against any type of editing that is not proven safe and effective before use in humans.

Q. But how does it prove that it is safe in humans?

A. Animal studies would have to be done.

Q. But at some point we would have to jump from monkeys to humans.

A. Yes, at some point, yes. When I started my doctorate, my first interview was with Patrick Steptoe and Robert Edwards, in Cambridge, after the birth of Louise Brown [in 1978, the first person born by IVF due to the work of Steptoe, a gynecologist and Edwards, a scientist]. Everyone was shocked – talking of a slippery slope and the end of the world and saying the scientists were playing God. And now there are millions of children born through IVF who are totally normal and perfectly healthy. They are not monsters.

Q. The red lines are always moving. Did you have red lines 10, 20 or 30 years ago that you no longer have?

A. No, I have faith in people.

Q. In order to study how embryos develop, Spanish scientist Juan Carlos Izpisua and his team have created embryos made up of cells from both monkeys and humans. What do you think of this type of research?

A. It is one of the areas where species are being mixed. A man with a pig’s heart genetically modified to be compatible has just died, for example. But these examples of xenotransplantation [transplant of organs from one species to another] are quite different from mixing human and animal cells in embryos. It is an area that disturbs me, but perhaps it disturbs me because I don’t know enough about it. I think I need more information.

Q. Some scientists believe that these experiments with ape-human embryos are “opening Pandora’s box.”

A. To say we are opening Pandora’s box is to return to the accusations of the slippery slope and playing god. It is very easy to use these evocative expressions for political agendas, it doesn’t help anyone to use this kind of language. Pandora’s box opens, very well, and? What do we do or what do we not do?

Q. What is the moral status of an ape-human embryo?

A. I have no idea, maybe I could talk about their legal status, but the moral…

Q. And the legal status?

A. There are all kinds of filters in the laws to distinguish between people and things or between people and animals. There are people who think that you only have to count the cells, to know how many belong to a monkey and how many are human. I do not believe that quantification can determine moral or legal status. We have to be very careful. We have always used animals for experiments, but we have never tried to transform animals into humans or vice versa. I think that would not be morally or legally acceptable.

Q. We can imagine a pig with a human liver, two human lungs and a human heart, but on the outside being a normal pig.

A. There are more than 100,000 people on the waiting list to receive an organ in the US, people who may otherwise die. If the animals are treated humanely, I think we should do xenotransplantation. Or, even better, why don’t people donate their kidneys, if they’re going to die anyway? In some countries, like Spain, there is automatic organ donation, but even then the doctors ask the families. Why do you have a law if you ask the family later? Don’t ask the family! It is legally accepted in a democratic society that organ donation is a good thing for all citizens, that they are humans helping other humans, and it is the law. Why not recover the organs in 100% of the cases? I hope to be able to donate all my organs.

Q. Your father was a Christian missionary. You said at a conference three years ago that you have been burned in hell many times. What did you mean?

A. I was at the Royal Commission on New Reproductive Technologies in Canada [created in 1989]. We listened to everyone and it was interesting, because a lot of religious extremists, anti-tech groups and extremist feminists came together with one position: that these technologies were morally wrong. So even though we had public sessions where everyone had a chance to speak, you were getting hate mail. They chose biblical language, like I should burn in hell, perhaps because they knew my father was a missionary. People can be quite cruel when they defend positions that they believe are morally justified.

Q. Do you still have problems with religious ideologies in your work?

A. Whether religious or not I find that extremist positions narrow my thinking, as if there were only one way of thinking and acting. They are practically anti-human positions, because they do not respect the beautiful complexity of human beings.

Q. One day in 2018 we learned that the Chinese scientist He Jiankui had created genetically modified babies. One morning will we find out that someone has cloned humans?

A. No, I think reproductive human cloning is one of the areas where there is almost universal consensus that we should never go down that road. It would create an element of industrialization in reproduction and turn people into things that can be copied. For me it is a red line.

Q. You don’t like doing science fiction, but surely you can imagine that North Korea’s dictator, Kim Jong-un, wants a copy of himself.

A. I find the idea that someone thinks they are so special as to think that there must be a copy of themselves so pathetic… I don’t think it will happen.

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