You can't predict alcoholism by genes
Svetlana Borinskaya on genetic tests, the search for criminals and pseudoscience
Is it true that scientists have finally found the "crime gene"? How did genetic databases help to find the "Golden State killer"? What influences a person more — genetics or upbringing? Are there many families in the world with an "aggression mutation"? What new pseudoscientific "trends" have appeared in Russia in recent years? Svetlana Borinskaya, Doctor of Biological Sciences, Head of the Genome Analysis Laboratory at the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences, tells.
XX2 CENTURY. Personal genetic tests are quite a popular service today. In general, does it make sense to take them to a healthy man or woman? Or is it worth taking them only in certain circumstances — for example, if a person is planning to have a child?
Svetlana Borinskaya. Let me first tell you what genetic tests are. Genetic tests are medical tests that are related to the state of health. There is a so—called "entertaining" genetics - for example, it can be used to find out whether the smell of urine changes after eating asparagus. It's interesting, but as far as I know, it doesn't affect your health in any way. You can also find out if a person is a carrier of the gene responsible for sneezing when in the sun. This may be important — because if a person is driving and the sun's rays suddenly hit him in the eyes, he may sneeze and not cope with the controls. But, most likely, people know about this feature without any testing.
There are tests of a non—medical nature - for example, to establish paternity or one or another type of close kinship. And also — genealogical tests that establish the origin of a person. Sometimes they are essential for health, but in most cases a person passes them for the sake of interest in his own pedigree.
For the sake of curiosity, you can do any tests at all. But if we are talking about a medical and genetic examination, then there are direct indications here - this is the presence of patients with hereditary diseases in the family, especially the presence of a couple of previously born children with hereditary disorders. Also, the spouses belong to certain ethnogeographic groups, in which hereditary diseases are often found.
XX2 CENTURY. For example?
S. B. For example, in Sardinia, as in other Mediterranean countries, the frequency of mutations of resistance to malaria is increased. And the variants of genes that give resistance to malaria are actually harmful. Without malaria, these gene variants disappear from the population very quickly — because their carriers have reduced fitness. If there is malaria, they do not die from it, unlike other people, and this gives them an advantage. But at the same time, if both parents are carriers of such a mutation, then the child is born with a rather severe autosomal recessive blood disease. These children used to die, but now they survive, but they need lifelong treatment. But I want the children to be healthy! And that's why a campaign on medical and genetic testing was conducted in Sardinia. What was it? If both mom and dad were carriers of the mentioned mutations, then the risk of having a sick child was 25%. Then they had an antenatal diagnosis, and if it became clear that they would have an unhealthy child, the parents were offered to terminate the pregnancy. And mom and dad have already decided whether to have an abortion or not.
As a result, in Sardinia, the incidence of this hereditary disease decreased by 50 times, which was both an economic burden on the country, and a burden on medicine, and, of course, grief for the family. And the child himself was not happy to have such a serious blood disease.
Ethical aspects are important here, because there are opponents of abortion, there are religious attitudes in this regard. And in some countries — for example, in Iran, where mutations associated with malaria resistance and leading to the disease are also common, if a child receives them from both father and mother — there was a rule — it was mandatory to undergo genetic testing before marriage. And if both parents were carriers of these mutations and could give birth to a sick baby, then they were not given permission to marry. This was the tactic of "improving" the population.
In general, there are unconditional indications for medical and genetic examination, for example, the presence of hereditary diseases in the family. Already born children with such diseases are also sent for such an examination, when it is necessary to establish or clarify the diagnosis and choose the appropriate treatment. But there are a number of questions for some types of testing.
XX2 CENTURY. Can you give an example?
S. B. If there is a case of breast cancer in the family, it is recommended to carry out BRCA gene mutation tests, which give an 80% chance of developing such a cancer. A famous case is Angelina Jolie. Her mother and aunt had breast cancer, and so she underwent an examination. A mutation was found in her, and as a result, Jolie agreed to preventive surgery — because breast cancer develops 10-15 years earlier in carriers of mutations and it is necessary to monitor it all the time so that it does not occur. All my life, every three months to undergo examinations! And if the cancer is missed, it can develop very quickly and the treatment will be a kind of lottery. Will it work out well or not? How quickly will metastases occur? In women with mutations, breast cancer is more malignant than in others.
But BRCA mutations are rare in the population. And among women with breast cancer, they are present in only 5% of patients. The rest have either mutations in other genes, or it is not clear at all what kind of genetic disorders led to cancer. And were there any genetic reasons at all —or maybe only environmental influences were to blame? Because you can "try hard" and even with the best genes "arrange" a disease for yourself.
Question: do all women need to be examined for the presence of "cancer" mutations? Some doctors believe that it is necessary, others — that it is not, because the mutation is too rare and a general examination is not required. There is less disagreement about whether to do a mastectomy if a mutation is detected. There is no cancer yet! But in some countries — for example, in Israel — it is believed that such a preventive operation is effective and significantly reduces health risks. If such mutations are detected in a young woman, she may be advised to give birth to as many children as she wants, and then have surgery.
XX2 CENTURY. On the Internet, I regularly come across offers of questionable research at first glance — for example, not so long ago I saw an advertisement for a genetic test that allegedly reveals a penchant for sports…
S. B. Tests that reveal inclinations to sports, professions or even cardiovascular diseases are such a "gray zone". It cannot be said that this is pure lies, but at the same time it cannot be argued that this is a scientifically based prediction. Because, as with breast cancer, there is a small proportion of diseases that is well explained by the presence of mutations — for example, there are such mutations of familial hypercholesterolemia. But many mutations increase the risk of the disease slightly, besides, prediction needs to be made by a variety of genes, that is, it is almost impossible to predict complex signs by five or ten genes. By the way, I recently saw a paper whose authors propose to select people for special forces on the basis of several genes related to behavior. Supposedly, by looking at what variants of genes a person has, it is possible to predict whether he will be psychologically stable or will break down and accidentally shoot someone. It is premature to make such predictions based on genes — science has not accumulated such data. And in the future it is unlikely to be possible — human behavior is too complex a sign. The exception is cases of hereditary diseases with behavioral disorders, they can be predicted by genes. But they are not so common that mass screening is justified.
It is also impossible to predict alcoholism by genes — there is no gene that determines the tendency to drunkenness. There are genes that increase or decrease the risk — but it is impossible to confidently predict from them whether a particular person will become an alcoholic or not. Here there is a problem of transferring the data obtained by comparing groups of people to predictions for an individual. For example, when comparing a large group of drinkers with teetotallers, five genes were identified that increase the risk of alcohol abuse.
It will be difficult to transfer this prediction to an individual — because, in addition to the five identified genes, he has another 22 thousand. And among them, maybe there are 55 who act in the other direction. And we did not take them into account when predicting!
Therefore, such predictions by genes, as academician Evgeny Konstantinovich Ginter, who for a long time headed the central medical and genetic institution of Russia, says, is "fortune-telling on the gene grounds."
This does not apply to hereditary diseases or features associated with a single gene. Several thousand such hereditary diseases are known, and test systems have been developed for hundreds of them. The well-predicted signs that are not related to diseases include the already mentioned ability to sneeze in the sun or the ability to digest whole milk (tolerance of milk sugar in adults). The only question is — how much money is a person willing to pay to find out such a feature?
And there are signs that are poorly predicted. But companies predict them — however, the prediction that we have a 3% higher risk of anything is a clinically insignificant prediction. This is statistically significant when comparing groups and is useful for understanding the molecular mechanisms of the development of certain processes in normal or in disease. But this is meaningless for an individual prediction! And when a company gives a 100-page prediction about health... it's not a fact that it can be used.
XX2 CENTURY. I often hear that doctors recommend that men and women take tests when planning a child for genes that lead to spinal muscular atrophy…
S. B. In the future, it will probably be possible to read the complete genome of a child and make a description for him of common and rare hereditary diseases and what risks he has more or less reliably predicted. Such a medical and genetic passport can be useful for health. When this child — let's assume that we are talking about a boy — grows up and is going to get married, his bride will have the same passport. They will check them to see if they have matches for harmful mutations — that is, whether the birth of a sick child is likely. If the probability is high, then measures will be taken to ensure that the child is born healthy. Even now it can be done — I'm talking about prenatal diagnosis.
But so far, few people have genetic passports. And when we want to be tested for the carrier of certain gene variants, we are talking about the price-benefit ratio. The ratio in each family should be considered individually. In the whole country, if we can diagnose a rare enough SMA disease, the state and people have money for it, plus the diagnostic condition is good, then it would be good to carry out this diagnosis so that fewer sick children are born or that treatment is started in a timely manner. But if the disease is extremely rare — for example, 10 sick children are born in the country per year, and diagnosis is expensive, then it is too expensive for all newborns to make a diagnosis so that 10 sick children are not born? This task is ethically justified — because every child's tear is an object of attention and care — but on a state scale, when resources are not unlimited, they need to be spent in a more efficient way. That is, to prevent one very rare disease and at the same time deprive financial support for the prevention of more common diseases… That is, to save 10 children and not save 10 thousand with another disease… This should be decided on the basis of the frequency of occurrence of the disease, its curability. Currently, five common hereditary diseases are being diagnosed in Russian maternity hospitals, for which there is treatment and for which it is important to start treatment early. Common ones are one in several thousand. These include phenylketonuria and metabolic disorders, where by introducing special nutrition, and the earlier the better, and other treatment measures, you can get a good result. For rarer diseases, the cost of saving one life increases very much. And for diseases for which there is no treatment, it is possible to diagnose — but it will still be impossible to do anything! The maximum is to carry out supportive therapy for the whole (sometimes, alas, very short) life.
XX2 CENTURY. Is it possible to find your distant relatives with the help of genetic tests?
S. B. You can! The family tree is built for all mankind. On the Y chromosome, on the male line, and on the mitochondrial DNA, on the female line. Some people are looking for their relatives with the help of tests, some are just interested in their family history. The police are interested in such data for solving crimes. Cases when the definition of distant kinship helped to solve serious crimes are known both in Russia and abroad.
XX2 CENTURY. Can you give an example when a criminal was found with the help of pedigrees?
S. B. For example, the story of the killer from the "Golden State" Joseph Deangelo, who was contacted through genealogical databases, is known. The police had a sample from the crime scene, they analyzed it. The policeman registered in the genetic database under a pseudonym and entered the genetic profile of the criminal. And I found his relatives there! And already through relatives established the identity of the killer. That is, when the policeman found relatives, he appealed to the holders of the database with a request to contact these relatives — their names are not visible in the database.
In Russia, too, investigations were conducted several times with the help of genealogical databases. The most famous case is about the identification of a terrorist who committed an explosion at Domodedovo airport in 2011. And we also know the case of a Novosibirsk pedophile who committed several attacks on girls for 10 years. And in a number of other cases, such an analysis provided clues to identify the perpetrator. Therefore, criminologists in our country work closely with geneticists.
XX2 CENTURY. As far as I remember, your colleague Oleg Balanovsky, who tragically died this summer, also dealt with this topic?
S. B. Yes, the genetic databases created by Oleg and his mother Elena Balanovskaya helped to establish the identity of the Domodedovo terrorist.
XX2 CENTURY. Sometimes I read news in the media, according to which scientists allegedly find crime genes… How much can this news be believed?
S. B. There is a well-known joke about the chromosome, which increases the risk of committing crimes. I'm talking about the Y chromosome. Because men are more likely to commit crimes.
And the search for crime genes itself was not crowned with success. Despite the fact that there are publications according to which some gene variants are more common in persons who have committed crimes… There was even such an interesting article by Finnish authors who found variants of genes more common in murderers. And in the USA, there have been attempts to justify a person for a committed crime or to reduce his punishment, because he allegedly has a gene that makes his behavior less stable.… It's not his fault that he has such a gene! Therefore, he should not be punished. But the criminal got it in full. In Russia, too, several projects have tried to find genes associated with aggressive behavior and serious crimes, to understand how murderers differ from others.
In rare cases, genes can really push a person to aggression. There is Brunner syndrome — named after the Dutch geneticist Hans Brunner, who examined a family in which there had been men with aggressive behavior for several generations. Brunner found out that they were suffering from a hereditary disease. Because of the mutation, the monoamine oxidase A (MAOA) gene did not work for them. And this led to violations of the regulation of behavior and increased aggressiveness. But at the same time, Brunner himself protested and did not want to call this mutation a mutation of aggression. He said that different men had different mutations in their behavior.
Talking about some kind of crime gene is still not worth it. In addition, there are not so many families with aggression mutations described in the world. Only four or five, no more. This is an extremely rare phenomenon! And this is the most studied case of a genetically predetermined behavior disorder in the direction of antisocial behavior. There are hereditary diseases that change behavior. But these are diseases! Not the criminal's gene, but diseases that manifest themselves in a variety of disorders, including behavioral disorders. So far, no killer gene has been discovered.
Although animal studies show that aggressive behavior has a genetic basis. And the friendly behavior of pets too. Novosibirsk animals, which were domesticated in the 60s - minks and foxes — are now well studied. Scientists have bred a line of domestic foxes and a line of foxes with increased aggressiveness. By analyzing their complete genomes, scientists have found the genes by which they differ. It would be very interesting to see the differences in these genes in humans.
Perhaps, just as changes in genes increase the risk of cardiovascular diseases, they can also increase the risk of aggressive behavior. But, as with cardiovascular diseases, a certain regime or lifestyle can reduce the risk, and lifestyle or upbringing can change the manifestation of genes that affect behavior. Now epigenetic studies are actively developing — these are studies of the regulation of gene activity at different levels, DNA methylation, the participation of microRNAs and some other processes that change the activity of genes and are more closely related to traits than the genes themselves.
XX2 CENTURY. What does affect a person more from the point of view of modern science - genetics or upbringing? Or is there a 50-50 influence here?
S. B. The influence is different for different signs. For some - 80 by 20, for others — 20 by 80, for others — 50 by 50. That's all — the average temperature in the hospital. But what we are is the result of the manifestation of genes in specific environmental conditions. This applies to any attribute. Let me give you an example: if all children are grown in boxes, then they will not have a difference in height. They will all be shaped like boxes. Because the environment will not allow genetic differences to manifest. And if children are raised without boxes, their growth will depend on genes. This is an illustration of the action of any attribute. For example, there are hereditary diseases that are clearly associated with individual genes. And when they began to study genomes, among the thousands of people studied, they found 13 people with mutations of classical diseases, but at the same time carriers of mutations of these diseases did not have. And why? Either other genes "buffered", or the environment influenced… We don't know. This is a very interesting subject of research.
XX2 CENTURY. For me, you are not only a respected geneticist and popularizer of science, but also an active fighter against various kinds of obscurantism. Tell me, please, what new pseudoscientific "trends" have appeared in the last couple of years?
S. B. Because of the covid epidemic, just a fountain of various obscurantism appeared. People are against vaccinations. People make absolutely fantastic assumptions about what should be treated. People say that it is not necessary to wear masks. It's just some kind of illiteracy parade, which has become very visible because of covid.
The apogee of illiteracy is an antiviral badge that supposedly releases chlorine dioxide and saves from covid. But after all, if the badge worked, it would first of all kill its owner: chlorine is still poisonous!
XX2 CENTURY. And finally, I will ask this question: in your opinion, are Russian journalists now helping to fight pseudoscience, or, on the contrary, more often contributing to its spread?
S. B. Scientific journalists help to fight obscurantism. And journalists in general — not always. In many publications, journalists, unfortunately, spread obscurantism — or simply illiterate the information.
But those scientific journalists with whom I had to communicate are usually highly professional specialists with high ethical attitudes. And interacting with them is just a pleasure, because they explain what I wanted to say better than me! Because they know the word, do not distort statements and always ask again when something is not clear. And they also send a text for approval, which is also very important. Such journalists are doing a very important job.
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