Mikhail Gelfand on paleogenetics
"We should not be afraid of ancient bacteria and viruses, but of modern ones
Ekaterina Shutova talked, XX2 century
Why is it so difficult to sequence the Andaman genome? Where in ancient times did the biggest "movement" take place? Is it worth waiting for scientists to isolate dinosaur DNA? How to raise a mammoth? And the Neanderthal child? What bacteria and viruses should be afraid of? Says the Doctor of Biological Sciences Michael Gelfand.
XX2 CENTURY. Why do scientists study ancient genomes at all? Is it just an interest in the past, or can ancient genomes tell something about us today?
Michael Gelfand. Basically, of course, scientists are driven by an interest in the past. Why are people interested in their history at all and are engaged in archaeology and paleontology? Then they study ancient genomes. I am constantly asked what is the practical meaning of paleogenetics and other sciences. But science is beautiful in itself, without any practical application. Life experience shows that fundamental science, which is engaged in learning about the world, pays off in the long run. Just as a public institution. The money that taxpayers spend on science through the state pays off — because in the end there are people who are already engaged in technology. It may be the same scientists, but this rarely happens.
The understanding of the world that we have thanks to scientists grows into various nishty things like gadgets and other wonderful things. Therefore, in principle, answering the question why science is needed, I would say this: so that people live better. But the question of why a specific study is needed cannot be answered, because no one knows what kind of research will be useful.
Why study ancient genomes for medicine? And the devil knows! Maybe the research will be useful in the end, and maybe not. But understanding who we are and where we come from is useful in itself. In general, it is useful not to be stupid idiots.
XX2 CENTURY. Mikhail, you talk about ancient genomes so often — for example, I was happy to listen to your lectures on this topic at Post-Science... and do you study ancient genomes yourself? Or is it just a hobby for you?
M. G. I have a couple of small papers on ancient genomes. But I don't do them professionally — I just follow the topic, it's interesting to me. To successfully study ancient genomes, you need to have access to primary data, and it's already hard to study the third—pressed serum - you need to be very smart for this. To do something amazing, new and interesting on someone else's data that scientists have already looked at, you need to be an inhumanly talented geneticist. I am not.
XX2 CENTURY. Are there any talented paleogentists in our country at all?
M. G. There are wonderful geneticists in our country, but I don't know any Russian paleogeneticists at all. Russia is such a raw material power. And this applies to all areas — including ancient DNA. Our contribution to paleogenetics is significant, but it consists simply in bones. A lot of articles feature Russian co-authors, but these are not evolutionary geneticists, but archaeologists.
On the other hand, there are wonderful population geneticists in our country — the deceased immediately comes to mind Oleg Balanovsky. There are good specialists in Ufa, Tomsk and other cities, they are well engaged in population genetics, but they do not work with antiquity, but with samples that are not tens of thousands of years old, but only thousands.
In addition, there are groups in Russia that successfully cooperate with those who have good technology in their hands. For example, they analyze ancient pathogens — they dig up burial grounds and cemeteries and are interested not in people buried there, but in bacteria, because of which people died. This is also an absolutely wonderful science, in which there is a tangible Russian contribution.
XX2 CENTURY. And what interesting things can be learned by analyzing the DNA of ancient bacteria and viruses?
M. G. Ancient epidemics are a big piece of history. And in general, the history of mankind was largely formed under the influence of epidemics. The most striking example is the Black death, the plague of the XIV century, which not only gave us Boccaccio's Decameron and other wonderful literary works, but also changed economic relations. Because labor has become expensive. Before the plague, there were a lot of people and the work was worthless. And then it turned out that there were few people — and in order for them to work, they had to pay more or keep them in better conditions. I am not an economist, but I have read very beautiful studies about how the plague affected the restructuring of the economy in the Renaissance.
Recently, a work was published with the participation of scientists from Kazan, who dug up the city of Bulgar, where there was also a plague — and it turned out that the disease was brought there from Western Europe. That is, at first, during the siege of Feodosia, the Turks threw plague corpses of opponents, infected the Genoese, the Genoese surrendered the fortress and rushed to their homeland, infected everyone there, and then the plague from Genoa spread across Europe. So, it turned out that the plague, which came from the steppes of Central Asia and the Southern Urals, got into the Bulgars by a "hook": first it passed through Western Europe, and from there it dragged itself through Russia to Volga Bulgaria. Although, it would seem, two steps from the steppes to the north — and here he is, the Bulgar. In my opinion, these conclusions are interesting in themselves.
Let me give you another example: when South America was conquered, most of the Indians died not because they were killed, but because they were infected. In particular, there was an epidemic of some terrible and incomprehensible disease in the city that is now known as Mexico City. It was the capital of the Aztecs and there were several epidemics — the worst one mowed down more than half of the population. Even the European plague cannot compare with such a result! And because it was so terrible, people described it all very colorfully. So colorful that it was impossible to understand what kind of disease it was based on the described symptoms. They sinned a lot on something — first of all, on smallpox. And then archaeologists excavated two cemeteries — one "worked" before the epidemic, and the other during the epidemic. And scientists have analyzed which bacteria live in the soil — not even in the bones, but in the ground.
XX2 CENTURY. And what turned out?
M. G. That salmonella live in the second cemetery, but there are none in the first! They dug up not under the paths, of course, but where there were burials. And so scientists learned that the unfortunate Aztecs died of typhoid fever. They hadn't met him before, apparently — and in the end they got such a kick out of it.
This knowledge is not very useful for modern healthcare, but from the point of view of our history books it is quite meaningful.
XX2 CENTURY. Recently in the public "Anthropogenesis.<url>" conducted a survey in which subscribers were asked to note which statements about animal cloning they encountered most often. The statement "Ancient bacteria or viruses can be stored in glaciers for millions of years, if they are thawed, then everyone is fucked" won…
M. G. This is nonsense. Firstly, because when you study the DNA of an ancient bacterium, you are studying the DNA of a non-bacterium. There are no whole bacteria in ancient corpses or in old cemeteries. And the DNA there is not a whole long wonderful molecule, but heavily degraded into small pieces. It's an art to reconstruct and study this ancient genome! In this sense, the frightened citizens are pleased to relax.
There is permafrost. Generally speaking, it is more interesting with permafrost, because both living cells and living viruses can be preserved there. But there is no reason to think that they are scarier than those that are now. Those bacteria that were isolated from permafrost are, in general, a story not of scientific failure, but rather of some kind of scientific disappointment. It turned out that these ancient bacteria found in the cores are no different from modern ones. Therefore, all the stories that a corpse was dug up in the permafrost or in Antarctica, and everyone who touched it got infected themselves and infected those who came to rescue them, and then the whole world died out... it's all nonsense. Life experience shows that it is much more dangerous to run around the tropics and eat anyone. We should not be afraid of ancient bacteria and viruses, but of modern ones, which jump on us from our excessive curiosity and gluttony. We are observing this. Look at all the wonderful and terrible diseases of recent times! The same acquired immunodeficiency got to people because monkeys were eaten… The coronavirus, again, jumped to us from bats, which either ate, or tried to use their droppings as fertilizer. If there's anything to be afraid of, it's our curious and voracious co-inhabitants of the Earth.
XX2 CENTURY. Do you think the coronavirus could have escaped from the lab?
M. G. has not presented a single serious argument in favor of the fact that people somehow manipulated the genome of this virus. And, according to Occam's razor, I believe that this did not happen. Different people said: "There it is, there it is, a smoking gun!" But it turned out that we are not talking about a gun, but about a stick that has been lying in the corner for twenty years.
The virus escaped from the laboratory or did not escape from the laboratory — this is not a question for me, but for the detectives. Let's imagine two situations. First: the Chinese Wan-Wan, Ivan Ivanovich, went into the forest and caught a bat there. I brought it to the market to sell for meat. And while he was butchering a mouse, he cut himself, got infected with the coronavirus and infected everyone else. The second situation: Postdoc Wan-Wan caught a bat to study it. I brought it to the laboratory, dissected it, accidentally cut myself, infected my colleagues first, and then the whole world. There is absolutely no difference in these two scenarios. But in the first case, we say that the virus came from the market, and in the second — that it escaped from the laboratory.
In general, the virus could have escaped from anywhere. But there are no arguments in favor of the fact that it was purposefully changed and made more terrible.
XX2 CENTURY. Let's go back to more ancient viruses?
M. G. Come on. In general, it amazes me that our compatriots are afraid that scientists will revive an ancient bacterium, but they are not afraid of the coronavirus that flies around them every day. They are not vaccinated, they are dragged everywhere without masks in large crowds… They don't care about anything. And the fact that scientists will revive an ancient bacterium is a horror-horror. That's what kind of porridge should be in the heads to reason like that?
I must say that over the past year and a half I have become a very big misanthrope. When I faced the abyss of human stupidity that we are now seeing with our own eyes... I have a lot of psychologists in my Facebook feed, and they scold me all the time: they say I offend anti-vaxxers instead of patiently persuading them. I can no longer patiently persuade, I have no strength! They don't feel sorry for themselves — they would feel sorry for children and the elderly. But no, nothing works. Apparently, the only way to force the population to vaccinate is to harshly treat the antivaxer to stick out his filthy muzzle, and they slapped his ears so that he hid it and did not seduce anyone with his bullshit. But gently and patiently explain "Vasenka, well, you're probably wrong, look — the temperature will rise a little bit from the vaccination, but if you get sick with a virus, you will go to the hospital on a ventilator, you will die on it, and if you don't die, you will become an idiot."
XX2 CENTURY. Is it really possible to become an idiot from coronavirus?
M. G. Coronavirus hits the brain very hard. While there were no vaccines, several employees got sick in my laboratory. After the illness, they themselves wrote that they work worse — they can't think for more than two hours in a row, they forget something.
But anti-vaccinators don't care about anything! The fact that elections are being rigged is normal. The fact that billions are being stolen is also OK. Some poisonous factory samples and landfills are normal. And here we are suddenly fighting for personal freedom and opposing vaccines!
XX2 CENTURY. And again about paleogenetics: did scientists manage to find out whether there were any global epidemics in ancient times? It is clear that fewer people used to live…
M. G. We know about many epidemics banally from history. The same Justinian plague is well known… Recently, a very beautiful work on the hepatitis B virus was published. It's not about an ancient epidemic, it's more about the fact that there were five lines of hepatitis B virus, and then there were only two ... And another one seems to have disappeared, but it seems to have been preserved somewhere - and now viruses of this line mainly infect people with suppressed immune systems. For example, AIDS patients. This line of the virus was a little warm somewhere, and now it has blossomed, because it turned out that for her, patients with immunodeficiency are the very thing.
Such studies do not completely reconstruct the history of ancient epidemics, but they say something about pathogens. There were works about tuberculosis. According to these works, people in South America had tuberculosis, but at the same time they had a tuberculosis bacillus that was not our standard one, but their own, which jumped over them from pinnipeds in general. That is, they caught some walruses, seals carelessly, and the bacterium passed on to them.
What else are scientists doing? They find out who was the causative agent of ancient epidemics, which are known to us from written history and are very colorfully described ...Unfortunately, I don't have much time, but otherwise I would love to read all these articles and make a review or lecture on them. Because this is an insanely interesting topic.
XX2 CENTURY. I periodically read foreign Twitter and I see that some anthropologists and archaeologists are dissatisfied with the conclusions of paleogenetics. The former accuse the latter of allegedly trying to make everything old! Have you ever encountered such a conflict between anthropologists and geneticists?
M. G. I can tell you about my own conflict with an anthropologist. With Stanislav Drobyshevsky. On the basis of molecular paleontology. Drobyshevsky wrote a book with errors, and when I edited it for the second edition, Stanislav took into account half of the edits, and half did not. And I and other colleagues had to ask the editorial board of "Bombora" to remove us from the scientific editors of the book. That was a conflict between a geneticist and an anthropologist!
In general, there were conflicts between the first and the second, and we passed them in the relations of classical zoologists and specialists who build molecular phylogenetic trees. When bioinformatics learned how to build good evolutionary trees based on protein sequences, it turned out that a lot of things in taxonomy had to be revised. Bacterial taxonomy in general all flew to hell! But it did not exist, by and large — the bacteria were classified mainly by external signs.
A lot of unexpected things popped up, for example, that multicellularity has occurred many times, and fungi are not lower plants, but closer to animals. A lot of new things have been revealed! And there was a lot of friction between scientists. For example: we found out that whales are a sister group of hippos. Zoologists got very excited and even started making various indecent gestures with their hands. They were shouting: And then molecular trees became even more reliable, besides paleontologists dug up new skeletons, and the hypothesis about whales and hippos became a common place. And before that, there was a fierce debate between zoologists and molecular biologists, including in scientific articles. So we've been through this! Well, now all zoologists themselves use molecular methods and successfully build trees — it's not so difficult, it's not a Newton binomial. And I think something similar will happen between geneticists and anthropologists. Sooner or later we will have an international and friendship of peoples!
XX2 CENTURY. How have the methods of ancient DNA research improved compared to the situation 10 years ago? What can we do now that we couldn't before? Maybe they learned how to extract DNA from more ancient bones? Or from the ground in caves? Or have they become better at cleaning ancient DNA from contamination?
M. G. You answered your own question. The technical base has really improved in recent years. And, accordingly, the methods are becoming more and more sensitive. And at the same time, they are all better protected from contamination. In addition, sequencing becomes trite cheaper!
Working with ancient pathogens is absolutely amazing. Because with human DNA, it is more or less clear: they took a human bone, drilled it out of the middle, everything. Usually, scientists take teeth and ear bones for this purpose. And then it turns out that a person died from some bacterial disease and decomposed all over. There are no soft tissues left! There was a plague, for example — so this plague sat in a person either in the lungs or in the lymph nodes. When we came to study the skeleton after thousands of years, there were no lymph nodes left. There is only one earth in place of the nodes! But it turns out that the DNA of the bacterium from which a person died is preserved in the soil and bones of this person. And from there they can be distinguished. This in itself is amazing, of course! Bacterial DNA is even isolated from tartar.
This is from technical stuff. And in meaningful ones, according to Hegel, quantity turns into quality. The more data we have, the more interesting we can draw conclusions. There are all sorts of wonderful stories about how often Cro-Magnons interbred with Neanderthals. And it feels like there was a metisation on every corner. It was not an isolated event, but quite a massive event!
The most wonderful thing that is happening now is when we see traces of unknown people in the modern genomes of different ethnic groups. Someone ancient, but at the same time we are not talking about a Neanderthal or a Denisovan. And this suggests that there were still some branches of humanity with which the ancestors of modern man happily spent time. Well, or not happily. Moreover, this is seen among the Andamans, in Southern India, Tibet, among the Central African Pygmies, among the Khoisan peoples in South Africa. All these fragments of unknown ancient things! At one time we tried to understand — are these unknown fragments from the same "unknown person", or from different unknowns? But so far we have failed, because there are too few fragments: enough to statistically show that there is an impurity, but not enough to study in detail. Maybe someone smarter will do this and find out if our ancestors interbred with some unknown joker, or there were several jokers? Maybe it was an erectus. Or Homo naledi, who is very much loved on your "Anthropogenesis".
To understand this, it is necessary to sequence more and more different ethnic groups. It would be good to sequence more, for example, Andamans, in order to study in more detail the traces of the unknown in their genome. But Andamans are very difficult to sequence.
XX2 CENTURY. Why?
M. G. Because when you start sequencing them, they shoot you in the eye with a bow. And you stop sequencing them.
In general, it is very interesting to study non-Europeans. Although it is also very informative to study Europeans — this way we can learn more about the history of Europe, understand where the Indo—Europeans came from, how large migrations of peoples took place, how the movement of agriculture took place - was it cultural borrowing or just territorial expansion of agricultural groups… This is also very interesting, but it is a story of about a thousand years' depth. Linguists with archaeologists and geneticists understood who was the native speaker of the Proto-Indo-European language, but it would be interesting to go back several thousand years and find out something about the language. Or to genetically confirm or refute the Sino-Dagestan hypothesis of Sergei Starostin — to look for common determinants among speakers of Chinese and different Dagestan languages, or even better, an ancient genome that would be suitable for the role of a common ancestor. That would be awfully interesting, too.
When we talk about crazy antiquity — about tens of thousands of years, it is interesting for us to study modern ethnic groups that could preserve traces of these historical events. Well, the ancient DNA itself is useful to study, and it is desirable to study DNA from different places. Unfortunately, nothing is preserved in the tropics…
XX2 CENTURY. But, as I understand it, it was in the tropics that ancient people mostly lived?
M. G. Aha, apparently, the main action took place there. But in the tropics, unfortunately, there is almost nothing left. And there's nothing you can do about it. This is physics and chemistry — you can't trample on them in any way.
In the tropics, of course, there was a lot of movement. Here's a look: We found the DNA of Denisovans in a cave in Altai and in Tibet. But we see Denisov traces most of all in the genomes of Melanesians — there are 5% of Denisov traces at all (Apparently, there are no more. The Filipino Aeta people have more Denisovan traces than the inhabitants of Melanesia – ed.). But when people went for a walk to Indonesia, and then to Australia, it is unlikely that they went to Altai on the way to make friends with Denisovites there. This is not a near hook, and there are all sorts of mountains there. Therefore, it is clear that the Denisovans' area was much larger. It most likely reached somewhere to the Indian Ocean - almost like Zhirinovsky's. Zhirinovsky dreamed of washing boots in the Indian Ocean — that's where Denisov's boots washed their paws. And thus Vladimir Volfovich's nose was wiped. Fifty thousand years ago.
When Cro—Magnons were walking along the coast — and this, as I understand it, is a common place — that Cro-Magnons were walking along the coast of the Indian Ocean to Australia - that's where they met with Denisovans somewhere. Because well, there's nowhere else! And there are no bones there, that's all. Because, firstly, the ocean level was changing — and there are no more parking lots that were on the shore. And secondly, again, the tropics — it's all over there twenty times. Here Vladimir Volfovich will go to wash his boots in the Indian Ocean, and there won't even be any bones left of him either! That would be a shame for him!
XX2 CENTURY. I often see statements in the media that scientists have singled out Dinosaur DNA. Is it even possible to isolate the DNA of such ancient animals? And is there any limit to antiquity — a million years, for example— when there is no DNA is no longer preserved?
M. G. The oldest DNA I've read about is about 700 thousand years old. It seems that there was someone even more ancient — I did not follow.
XX2 CENTURY. Whose DNA are you talking about?
M. G. The horse from permafrost.
Now about dinosaurs: it is clear that they cannot be in the permafrost. Because in the permafrost, in principle, there can be no cold-blooded living beings, no matter where they come from! Another thing is that some dinosaurs were warm-blooded — at least those from which birds later turned out… But nevertheless — the probability of finding a dinosaur in the permafrost is small. And in general, it's still not a million years, but 70-80 million. Therefore, I think the hope for dinosaur DNA should be abandoned. And don't read the media reports that talk about it. Because it's nothing.
XX2 CENTURY. But recently scientists published an article…
M. G. Apparently, you're talking about Mary Schweitzer. If I understand correctly, she is engaged in mass spectrometry and collagen proteins. And ten years ago she published very sensational articles that were strongly criticized by the professional community. I am not an expert in this topic, but the criticism was very harsh and public, even letters came to Science. I interviewed a professor at the University of California, San Diego on this topic Pavel Pevsner for the "Trinity Variant".
Since then, other works have also come from Schweitzer — but there is no reason to think that they have anything to do with reality. Although her articles, of course, still make sense to discuss. And other publications are mostly outright nonsense. A few years ago, for example, some great Altai scientists found some ancient DNA of an ancient Altai pine tree and happily created some hype about it. But everything was resolved — and no one has heard anything more about these scientists since then. And there are a lot of such stories!
Maybe journalists sometimes misunderstand scientific articles — this often happens. Here, about the same mammoths, there is a lot of hype — it's just that media employees misunderstand even meaningful research and lose details along the way. When scientists insert mammoth variants of the gene into an elephant's cage and see if it has become more resistant to cold, they already write in news feeds: "Yakut scientists have cloned a mammoth."
XX2 CENTURY. Do you think that in six years mammoths will really be walking in Altai? As foreign geneticists promise us…
M. G. No, no mammoths will walk anywhere. This, again, is nonsense. Of course, theoretically it is possible to genetically modify an elephant so that it has a certain number of variants of mammoth genes, and hope that this elephant will be adapted to the conditions of the tundra - but this will not happen in six years, firstly. And, secondly, there is a problem there…
XX2 CENTURY. Which one?
M. G. If you want to raise a mammoth, then you first need to reconstruct the genome of the common ancestor of the elephant and mammoth in a computer, and then go through the entire evolutionary path first from the elephant to the common ancestor, and then from the common ancestor to the mammoth. Of course, there is no law of nature why this cannot be done. The problem is that elephants live a long time, they have puberty late, no grant is enough to deal with them.
Another difficulty is this: there is such a phenomenon in genetics — epistasis. It is well studied. Epistasis consists of something like this. Let's say we have two organisms — an ancestor and a descendant, which differ in two places. It is clear that these two mutations could not occur at the same time, there was first one, then the other — so, it turns out that evolution could only go one way — that is, mutation A had to occur first, and then mutation B. And in reverse order, first B, and then A, it cannot be: the intermediate state (only B) is poorly adapted, its carrier will not survive. It was shown on the resistance of bacteria to antibiotics: we looked at two variants of some kind of resistance gene - one to the old, the other to the new antibiotic, and they differed in five positions — and it turned out that these five substitutions had to occur in a strictly defined order so that evolution could take place and that the intermediate variants were also good.
What does this mean? That when you turn an elephant into a mammoth, you need to take care not only to correct all the differences, but also to correct them in the right order. And how many of these differences are there? The differences between an elephant and a mammoth are about 1%. They differ about as much as humans and chimpanzees. The size of the mammalian genome is about 3 billion base pairs, one percent of 3 billion is 30 million. And this is a hell of a lot! Of course, not all of them are significant — most of them are probably even insignificant. Because most of the differences even between us and chimpanzees don't affect anything at all. The problem is that we never know in advance which differences affect what. We do not understand genetics so well, and especially mammoth genetics, to say: this position, which differs in mammoth and elephant, affects some external properties - phenotype, or does not affect anything.
And without this, to repair 30 million differences, the repair machine will dry up. Investors will get tired of waiting. What are smart scientists doing now? They are looking for those differences that obviously have a functional meaning — for example, in genes associated with maintaining a temperature regime. It is clear that these genes are important for the "transformation" of an elephant into a mammoth. They change the elephant variants of the gene to mammoth ones, and then they look at whether the cells have become more resistant to cold or not.
But even if we imagine that we changed all the options in an elephant egg to mammoth ones, and then hooked an elephant, it's not a fact that she takes out a cub! Because you can't plant a human embryo in a chimpanzee and hope that she will have a baby. But the level of genetic differences is about the same. Therefore, the moral is this: the promise that in six years a mammoth baby will cheerfully stomp on the tundra is a lie. Who made this statement at all? Representatives of the company or "talented" journalists?
The fact that a genetically modified baby elephant, close in its genotype and phenotype to a mammoth, will walk in a zoo, carefully covered with a blanket - well, this can be. But whether he will be declared a mammoth or not is a matter of PR, not science.
XX2 CENTURY. And the same can be done with a Neanderthal child?
M. G. You can! And, moreover, it's even easier: because there are much fewer differences between a Cro-Magnon and a Neanderthal than between an elephant and a mammoth. But, again, we have a serious ethical ban on human genetic engineering. And it is right that he is.
Therefore, I hope that no Neanderthals will appear in the near future. Although this will not happen in the near future also for technical reasons.
XX2 CENTURY. And I thought that scientists would be happy if a small Neanderthal was born, which could be observed…
M. G. Who could be tortured! Listen up! Dr. Mengele, as you know, has done a lot of wonderful science, as well as a lot of nonsense. But for some reason, scientists are not happy about this.
XX2 CENTURY. How to explain to a layman who is obtained as a result of crossing a Neanderthal and an ancestor of modern man?
M. G. In the first generation is a hybrid, 50% is a Neanderthal, 50% is the ancestor of modern man. In the second — a quadroon. In the third — the octoroon. Here is Alexander Sergeyevich Pushkin — who is he? His great-grandfather was Abram Petrovich Hannibal, an Arab of Peter the Great. A real patented Afro-African, as it is fashionable to say now! But Pushkin is an octoroon.
In general, let non-specialists look in the mirror and see what happened from crossing Cro-Magnons with Neanderthals.
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