About genes and not only

"There is no addiction gene, as there is no schizophrenia gene"

Ekaterina Drankina, Plus-one.ru

In 2020, the Nobel Prize in Chemistry was awarded for the CRISPR/Cas9 genome editing method. This technology opens up vast prospects for humanity in the fight against severe genetic diseases, but also raises new ethical questions. Plus‑one talked with Konstantin Severinov, professor at the Skolkovo Institute of Science and Technology, head of the laboratory at the Institute of Molecular Genetics of the Russian Academy of Sciences, about how the human gene pool is changing, whether there is "bad genetics" and whether the coronavirus can change us as a species.

Konstantin Severinov. Photos from the personal archive.

– The coronavirus pandemic is not the first, but a very large–scale clash of humanity with a powerful opponent of this kind. Can this meeting change our genetics?

– If we are talking about whether the genome of people who have been infected with coronavirus will change and whether they will transmit these changes to the next generations, then the answer is probably not. The virus is "made" on the basis of ribonucleic acid (RNA), and our genes are based on deoxyribonucleic acid (DNA). The transition from RNA to DNA is not impossible, but it happens extremely rarely.

You can look at the question differently: if you imagine that those who die have some special genetic properties, then, probably, the number of people with such properties will decrease after the pandemic. As a result, their genes will be less represented in the next generation. But that probably won't happen either. The vast majority of deaths still occur in the elderly, not of childbearing age.

– Is it possible that there are people who, precisely because of their genetics, are "tasteless" for this virus? After all, there are cases when, without antibodies, people come into contact with patients and do not get infected.

– This is, in principle, possible, but whether this is actually happening with the coronavirus, we do not know. In the case of the HIV pandemic, which has been with us for more than 35 years, scientists know that some people are less adapted to infection with the virus due to genetic characteristics. It was in order to create a person with increased resistance to HIV that Chinese biologist and biophysicist He Jiankui attempted embryonic gene editing in 2017.

– WHO warns that the next pandemics will be even more dangerous due to the growing resistance of microbes to antibiotics. Is there anything we can do about it?

– The golden age of antibiotics occurred in the 1950s and 1960s. In those years, most of the drugs currently used were discovered and put into practice. However, very soon doctors began to notice that pathogenic microbes are increasingly resistant to antibiotics. Now there are even more multidrug-resistant bacteria. Many people die from complications of covid caused by bacterial infections, simply because none of the available antibiotics works, is not able to suppress the growth of pathogenic bacteria.

Antibiotics in nature are used by bacteria and fungi in order to fence off a small area on which they will live and not let others in there. It is obvious that the cell that secretes antibiotics outside itself must be resistant to them. And indeed, antibiotic producers have genes that provide resistance to this antibiotic. Unlike us, bacteria exchange genes easily. As soon as we begin to widely use antibiotics, bacteria of different species very quickly "share" with each other "useful" resistance genes and displace bacteria that do not have it. You can search for and put into practice new drugs, but the problem of bad infinity will remain – resistance will inevitably arise.

– Can some alternative to antibiotics be invented?

– There are people who believe that bacteriophages can be used as an alternative, that is, bacterial viruses that, unlike antibiotics, very selectively kill only certain types of bacteria (or even specific strains of one species). Interestingly, this "medicine" is able to multiply as long as there are cells sensitive to it. In general, chic, brilliance, beauty, but in fact there are a number of reasons why, from the point of view of modern technologies and the organization of the healthcare system, industrial production and use of bacteriophages is ineffective. For example, bacteriophages eventually dissolve an infected cell, and the toxins it contains end up in a person's blood. The human immune system quickly learns to recognize bacteriophages and destroy them. In addition, bacteria have a lot of ways to become resistant to phages – this happens even faster than with antibiotics.

– Let's talk about bioethics. You mentioned the Chinese scientist He Jiankui, who edited the genes of embryos. For him, the experiment ended in prison. How will the topic of human genome correction develop in the future?

– On the one hand, I think the high-level English bioethical committee has recognized in principle the possibility of correcting human genetic diseases. It's clear why. There are severe genetic diseases that cannot be cured except by gene editing. There is a corresponding CRISPR/Cas9 technology – gene scissors. But then questions arise, since there are no guarantees that the following experiments, like the one conducted by He Jiankui, will be successful.

Let's say we want to rid humanity of some genetic disease - for example, cystic fibrosis. It would seem that it's a matter of business: to take and change a damaged copy of a gene for a good one with the help of gene scissors. But the technology can only be applied to a fertilized egg, if we are talking about a person who has already been born, billions of cells of his or her lungs will need to be changed, and this is impossible now. And if you edit a fertilized egg, plant it to your mother (native or surrogate – it doesn't matter) – then all the cells of this new little man will not contain the mutation responsible for the development of cystic fibrosis, since all the cells of our body contain the same DNA as was in the fertilized egg.

The problem is that we cannot guarantee that when we change some, from our point of view, incorrect DNA sections with CRISPR/Cas9, we do not change anything else. Gene scissors can misfire, which can lead to undesirable and unpredictable consequences. There is a problem: who will be responsible for this, who will support such sick children, what will be their rights, who should they sue? There is another question – how ethical is it to treat a disease that has not even developed yet and may not develop. After all, no one has asked these people – because they are not yet born.

Ethical barriers are associated with the fact that society is suspicious of everything new. And that's right. But the spread and adoption of technology often "retroactively" solves ethical problems. In the 1970s, when in vitro fertilization first appeared, everyone was screaming: "Horror! Horror!" But the end of the world did not happen, and the boundaries of what is permissible have expanded. I think this will happen with the technology of gene editing.

– There is evidence of a greater prevalence of certain diseases among peoples seeking to preserve their national identity. It turns out that gene scissors in such cases will be especially useful?

– I repeat, this is a rather complicated thing. For example, Jews have a high frequency of Tay-Sachs genetic disease (the enzyme hexosaminidase A ceases to be produced in the child's body, the lack of which leads to the destruction of the brain and spinal cord. – Approx. Plus-one.ru ) than other nations. But the "cure", the normalization of this gene, may lead to undesirable unplanned consequences. After all, a variant of the gene that can lead to this severe neurodegenerative disease, in certain contexts, leads to a higher density of nerve cell contacts, which, in turn, can affect, for example, cognitive abilities. Or take the case of Stephen Hawking. We can't be sure that if he was healthy, he would have become what he has become.

– Is it possible to predict that due to all these risks, humanity will eventually abandon the traditional way of making children? Through a test tube it looks somehow more reliable.

– I want to believe that there is not. Anyway, it will be sad. In fact, the traditional method is very reliable. Nature has created mechanisms of "foolproof": it consists in the fact that we have a double set of chromosomes. In order to give birth to a child with a genetic disease, it is necessary that both parents give him damaged copies of the same gene. The vast majority of people, even if they are carriers of some serious diseases, have changes in different genes.

– How do you feel about such a concept as "bad genetics"?

– For me, this is a social construct in the minds of a privileged class, or people who consider themselves to be such. They consider themselves carriers of the genes of success, intelligence, and so on, and representatives of the lower classes – carriers of genes responsible for some unsightly dependencies, bad inclinations... In fact, there is neither one nor the other. There is no addiction gene, just as there is no schizophrenia gene. There is some genetic component, but we cannot clearly determine which gene it is, which combination of typos/mutations in our genomes causes such complex properties. All the talk about the genes of intelligence, genes of the ability to tennis or swimming and so on are urban legends.

– In general, is the human gene pool deteriorating or improving?

– It's not very clear what to compare it with. The number of mutations that negatively affect the fitness for life in the savanna, where we originated as a species, is higher in modern humans than in people of the distant past. For example, I have hereditary myopia, and at the dawn of humanity I would have had no chance to pass on my genes to offspring, I would have been eaten by a predator or killed by tribesmen before puberty. But modern man has a huge number of crutches: cultural, social, physical and medical. Therefore, on the one hand, people who would not have survived earlier pass on their genes to their offspring, and on the other hand, we do not give birth to 10 children, as before, but one or two, because we no longer need to play evolutionary roulette and see who will survive. But I wouldn't say that the gene pool is getting worse: it's just changing. We are becoming more adapted to life in cities, in the information society, and not where we originated as a species.

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