A reasonable man liberated
Can gerontology be considered a God-pleasing thing?
And at the same time, he is a dissident in science, who decided to challenge not only colleagues, but also the fundamental limitations of human nature – aging and death.
We are sitting in one of the laboratories of Moscow State University and discussing Skulachev's book "Life without Old Age", which publishers do not want to release in the full version in any way – they are afraid to overload the readers' brains with science.
– So much has been written about the fight against aging of all nonsense and horror! – complains Skulachev. – I would not like to be on a par with typical authors who talk about this topic. Now gerontology is a very weak field of science, there is an extremely low level of research. Until now, one of our main tasks in this area is to defeat the prevailing view that the fight against aging is hopeless, to dispel the myth that aging is inevitable and therefore cannot be treated. When gerontologists are going to drink, they raise the first toast "To the success of our hopeless cause."
– Does the atmosphere of hopelessness repel talented scientists from this field?
– It's not just that. This hopelessness is exploited by geriatric doctors. If you have appendicitis cut out and, God forbid, you die, then your relatives will sue this surgeon. And if you are being treated for aging and dying from it, who will throw a stone at the doctor? Geriatrics is an absolutely guaranteed income, without risk: after all, it is believed that nothing can be done by and large, you can only alleviate suffering. And a lot of unscrupulous people earn their bread from aging. I was asked at the time: "Why are you doing oxidative phosphorylation?" I answered: "Because a party comrade will not pronounce such a thing and will not be able to give me instructions on how best to engage in oxidative phosphorylation." And everyone is engaged in aging, who is not lazy. Even they tried to add some kind of Russian condor method to my book: using the energy of the sun, earth and water, something like that. Moreover, people do not hesitate to bring me my book with this text as if nothing had happened.
– But you are a white crow among fellow scientists, aren't you?
– I am a dissident in the world of aging theories. Until now, the vast majority of biologists believe that aging is an accumulation of random errors. And I am sure that this is following a certain program laid down in each of us. However, my project is now at such a stage that I am no longer interested in disputes with opponents.
Programmable death– Does your theory explain aging better?
– You see, the system we are trying to explain is extremely complex and insufficiently studied. Are you a biologist by training?
– Psychologist.
– It should also be obvious to a psychologist that if the system is very complex, then its behavior can be explained by any theories.
– That's right, psychology is full of theories that can explain anything from their bell tower.
– That's the same thing in biology. Aging is easy to explain by one theory or another, but it is not yet possible to prove who is right.
– What then inclined you to the opinion that aging is a program?
– A very simple thing. There are thousands of examples of how a living being carries a deadly program. I just have to put forward the hypothesis that one of these programs is the aging program. And if it is a program, then by stopping it, you can cancel aging. By the way, we already know how to break the program in case of programmed cell death.
– And what are these examples of deadly programs?
– There is a huge group of scientists in biology for whom it would be obvious that aging is a program. Nerds. There are annual plants, there are a huge number of them, and it's clear to the hedgehog that they are dying due to the program that they have. They have already found a substance that kills them – it is formed in the seeds, it is abscisic acid and some other hormones that travel from the seed to the leaves and kill the leaves. The leaves fall off, and the plant dies.
– Isn't it the winter cold that kills them?
– No, it happens much earlier and even in the warmest conditions. And if you remove the seeds, the plant becomes perennial. Soy, for example, or rhesus. And invertebrate zoologists also know perfectly well that the death of an organism can be programmed. Invertebrates have some examples! The female mantis bites off the male's head at the end of sexual intercourse. Previously, even scientists were horrified how nature created such a soulless monster that eats a beloved creature. Then it turned out that in these species of mantises, ejaculation requires that the head be removed, cruelty and gluttony have nothing to do with it. But vertebrate specialists are engaged in gerontology, these examples are not close to them.
– And how did you come up with this idea?
– Under Soviet rule, I lived in an ivory tower because I didn't want to be led by party comrades. I have always done only what I wanted to do, all my life – I am a happy person in this sense. But when this dictate collapsed, I decided to do something as useful as possible for people. It was then that I came across August Weissmann's idea that death is an invention of evolution. Back in 1882, in his famous lecture on the nature of aging and death, he expressed the idea that everyone carries the seeds of death, such a time bomb. I was so struck by the beauty of this idea that I read everything that was about it – and there were mostly slops that were poured on Weisman until he, in his old age, almost blind, renounced this most vivid idea of his.
Inspired by this idea, I decided to make a substance that will break the aging program. Then I began to think about how such a program could be arranged. All my life I have been engaged in breathing, oxygen consumption by organisms. Everyone knows that without oxygen, the brain is already dead in five minutes. But I discovered that there is another breathing, harmful, which forms a poisonous form of oxygen. And then I thought: my God, this is exactly what the aging mechanism can be – the body itself forms some kind of poison that slowly brings us to the grave. Then I found out that this hypothesis was first put forward by Denham Harman back in 1956, but he did not believe that poisoning was programmed, but thought that it was an imperfection of nature. However, I agree with Francis Crick here, who said that every biologist should understand that evolution is much smarter than him, and blaming something on the imperfection of evolution is the last thing. This is not a flaw, but another elegant mechanism of evolution!
Why aging is necessary– Why is aging necessary for evolution?
– It is absolutely clear to me that the limitation of life is a purely evolutionary adaptation. I once found a wonderful aphorism in Aesop that a hare will always run away from a fox, because for a hare it's a matter of life and death, and for a fox it's just a matter of lunch. My father was an amateur hunter, he had already died by that time, and I asked one of his friends: do foxes really participate in the natural selection of hares? After a long discussion over a glass of tea, it turned out that the hunters believe Aesop was right, indeed hares always run away while young. Only old hares can be eaten by a fox, they run slower.
And then everything became clear to me – the hare is getting old in order to increase the pressure of natural selection! Here there is a smart hare and a stupid hare, here they will breed stupid and smart hares while they are young, because there is no animal that would distinguish them, they will run away from anyone you want. But gradually sarcopenia occurs, that is, the number of muscle cells in the muscles decreases and the hares run slower and slower. And now a fox will eat a stupid hare that does not know the habits of this orange beast, he will not breed stupid hares. And the clever one will get away from the fox by cunning and breed hares. My brother, a physicist, immediately made a simple program showing that in just five generations, with a sufficient number of foxes, all hares will become smart.
– In the real world, hares don't get very smart.
– Do you think hares are so stupid? You understand a lot! They're running away from foxes, don't forget.
– It turns out that aging is necessary, because due to the rapid change of generations, evolution is faster?
– I don't have a perfect answer to this question. According to Darwin, there is a selection of the fittest. And the one who does not age and does not die is more adapted.
– Is there only one aging mechanism?
– This is a very difficult question. I think that the central mechanism is one, a kind of samurai sword for suicide. But there are some appendages to it, like cancer. Cancer is also a special program, a quick mechanism of suicide. Maybe there are several parallelized mechanisms. But the fact that there are animals that do not age shows that it is possible to defeat these mechanisms. Otherwise, there would be no naked diggers. For us, a naked digger is a light in the window.
Make a naked digger out of a man– Are there mammals that don't age?
– There are those who live for a very long time and they have not shown any signs of aging. Some bats, whales, large turtles... there are few such creatures, and they are usually devoid of serious enemies, freed from the pressure of natural selection. Some big poisonous toad, for example. No one eats her, no one threatens her. She has reached a certain level and now does not age and does not evolve, quite happy with herself. It's because she's so terrible.
– And the evolution of naked diggers has slowed down?
– Yes, this is also the rarest case when an animal managed to find a niche where it has almost no enemies. Most of the diggers are turned off from breeding like worker ants – they explore the territory and fight, mostly with each other. Only the queen reproduces, who lives on everything ready in the center of the labyrinth they have dug – she always has food, she is protected from snakes and hostile diggers who could come and mess around.
– A digger can't die of old age?
– No one knows. Rochelle Baffenstein in the USA began researching naked diggers 33 years ago, and the diggers she caught in Africa are still alive, although animals of similar species do not live more than three years. Some of the diggers died in fights with other diggers. Their incisors are so powerful that they gnaw through concrete, so one bite cuts the victim in half. Even special plastic is made for them, which cannot be chewed through. At the same time, the digger himself is the size of a mouse.
– Does a naked digger not age in principle, or does it somehow age?
– He has no senile diseases. More precisely, some still found, for example, typical for kidneys, but they pass easily, diggers do not die from them. By the way, my whole project is not so much about prolonging life as about improving its quality. We want to make a naked digger out of a man, who, if he dies, is cheerful!
Maybe the digger is getting old somehow, this is a very difficult question - and this is also one of the troubles of our region. Working in biochemistry, I usually put an experiment in a day – I started in the morning, and by the evening I was already washing dishes. I really like to wash dishes – you stand in a white coat near the sink, the experience is over, and you can think what happened, no one bothers you, everyone has already left. And tomorrow – the next experience. But human aging lasts for decades, you can't put an experience in a day here. I connected my sons to the research and started working with my eldest grandson – he is still a schoolboy, I gave him my book to read and suggested writing down the questions that arise. Maybe the grandson will wait for the main result of our research – the victory over aging.
When to wait for a panacea
– What will be the treatment for old age?
– I have a dream. I keep remembering how the Swiss got smarter. Your generation has not caught this time, and in my youth it was believed that the most stupid people in the world were the Swiss. And indeed: among those who lived high in the mountains, there were many people with cretinism, small stature and mentally handicapped. And there were a lot of jokes about the stupidity of the Swiss. Then we found out the reason – there is too clean water, there is practically no iodine in it. A law was passed to add iodine to salt – now you can't buy table salt in Switzerland without adding iodine. And all over the world, just in case, they began to add iodine to salt. The cretins disappeared – it was so amazing and so cheap! So: I think that the remedy for old age will need to be added to table salt in the same way as iodine, and people will take the geroprotector just with food.
– I have repeatedly heard reproaches in your direction that you promised to defeat aging, and as a result came up with only eye drops.
– It is impossible to think of a more unfair accusation! Yes, we started with the eyes, with an old previously incurable disease – dry eye. It is very slow, but widespread: 9 million patients in the United States, 25 million in Japan, where for some reason it is more brutally rampant. Tears disappear, and instead of them a viscous liquid drips, first once a day, then twice, then fifty times a day. If they drip more than a hundred times a day, a wound occurs in the eye due to an immune response, and the eye has to be removed. We started with the eyes simply because it is much easier to get permission for eye drops than for a medicine that is taken by mouth. In drops, the active substance, the antioxidant SkQ, is contained in negligibly small doses.
SkQ, unlike other antioxidants, penetrates into the mitochondria – it is there that toxic reactive oxygen species are formed. It is important that SkQ does not touch reactive oxygen species in other parts of the cell. This is a terribly delicate issue, because evolution has adapted this poison not only for aging, but also for a lot of useful things. This is such a convenient transfer component in different regulatory circuits, we will not be able to live without it.
We have now submitted a request to the Ministry of Health to allow our medicine not only to drip into the eyes, but also to take it through the mouth. After our success with a dry eye, there was a chance to get permission quickly enough.
– So you want to use this medicine as a geroprotector for the whole body?
– It will still be prescribed for the eyes, although it will affect the whole body. Then, hopefully, we will start releasing SkQ as a cure for neurodegenerative diseases such as Alzheimer's and Parkinson's. We can't register geroprotectors. Recently, an appeal was written by several of the world's most famous gerontologists demanding to allow the registration of medicines that help from the entire group of senile diseases – that is, medicines for aging. While aging is not considered a disease, it turns out that we want to create a panacea, a cure for all diseases, and this is considered something impossible, like creating a perpetual motion machine. But in fact, it will not be a cure for everyone, but only for age-dependent diseases.
– How long will we have to wait?
– Such things are not done quickly, we must act carefully. SkQ has an amazing power of effect, a million times stronger than other antioxidants – what if they started dying or going crazy from it? Therefore, we started with eye drops, in which SkQ is contained in an extremely low concentration.
We made eye drops amazingly quickly. I drew this substance on a piece of paper somewhere in 2003, and in the same year we synthesized it. Hellishly difficult cleaning turned out to be. But it needs very little. At that time, we thought at first to release it for animals as a veterinary drug, but then we were persuaded to skip this stage, immediately make drops for people. So, then we calculated how much of this substance is needed per year for everyone who has old dogs, cats and horses – 4 grams for the whole country!
Then we conducted clinical trials on cataracts and glaucoma and also got positive results. Now we are starting clinical trials on macular degeneration, and in animals we are studying how the substance affects Alzheimer's disease, diabetes – by the way, excellent results on diabetes in mice, as well as on the effect on the rate of wound healing. And now we are promised in the Ministry of Health to include at least cataracts in the list of diseases that SkQ helps.
– Does the cataract disappear?
– Disappears, but not all types. The question of age is also important here. For example, if a rat is more than two years old, the substance ceases to act. But despite my age, I managed to get rid of cataracts.
– Do you take SkQ in a disciplined manner every day?
– I accept, yes. As an inventor, I have the right to do what I want with myself. I don't need any permission from the Ministry of Health for this.
What is the most interesting thing in biology– You created the Faculty of Bioinformatics at Moscow State University in 2002, when it was not yet clear that this field would play a central role in biomedicine and in modern science in general…
Do you still know in which areas of biology the central events will unfold in the near future?
– Not just bioinformatics, but the Faculty of Bioengineering and Bioinformatics. Bioengineering in our understanding is an attempt to engineer something better than nature. This is very important! The SkQ project is also about this. I am very proud of this faculty. Last year we had the highest passing score at Moscow State University, the hardest thing was to come to us. Very strong guys are coming – out of thirty places this year, five were taken by the winners of the All-Russian Biology Olympiad.
And I do not know of any other faculty where the ideas of combating aging would be popularized. As the dean, I always dedicate the first lecture for first-year students to this. Yes, by and large I can't talk about anything else – it's called dominant. Pavlov said: "All real scientists are sick people. They are sick of the dominant." I am a man of science, and the dean is generally unfit.
– Where in biology is the most interesting, the most promising thing happening now?
– I always do the most interesting things. Of course, this is an attempt to stop aging. Not even just aging, but counterproductive programs of the body in general – for example, the biochemical suicide of the body after a severe crisis. This is such a radical defense against reproduction – the suicide of those in whose DNA mistakes could have been born. The body monitors temperature, sugar levels, the level of certain amino acids – many parameters. And there is, apparently, some acceptable interval for key parameters. As soon as they go beyond the interval, it is a signal to commit suicide. I once came up with such a new biological law and called it "samurai": it is better to die than to make a mistake. As soon as there is a strong chance of making a mistake, the signal for death goes. Now I am just sure that this program of rapid suicide is working in us with the help of some mechanisms that are not yet known to us.
– Maybe depression is also one of them?
– By the way, our substance stops near-death depression. There is such an expression – "pouted like a mouse on the rump." I didn't understand what it meant before. Why a mouse? Why are you pouting? And it turns out that the mouse about ten days before death loses all interest in life, is no longer afraid of anything. It becomes almost motionless. Her fur is standing on end. And she's lying like a ball where this depression caught her. You can put a bunch of millet next to it – the mouse won't touch it. She wasn't pouting on her rump. She pouted at all. And this condition is removed by our substance, it was recently shown in Sweden. Our mice die cheerful.
– And how do the grant-givers treat you?
– As soon as we started the project, they immediately stopped giving us grants. Academies do not give money for eternal youth. Everyone tells me: just don't say in any case that it's anti-aging. And how can I not talk? Now, however, they slowly began to give again.
But in general, Russia has very favorable conditions for our project. In the USA, there is a tougher attitude to dogmas, it is much more difficult to overcome dogmas there. By the way, when they talk about the Russian national idea, I always notice that it is completely clear what it is – in free creativity. The higher classes have been selflessly engaged in creativity in our country quite recently. Poets and scientists were wealthy people and did what they were really interested in. Then there were no rich people, but Soviet research institutes were still selflessly engaged in creativity. Now we have been thrust into capitalism and are trying by all means to eradicate this wonderful tradition. But the grant system is killing great science. The grant system is good in order to support the average science and eliminate the bad one. And real scientific breakthroughs need to be nurtured in some other ways.
– Are there any chances that a national anti-aging program may appear in Russia?
– Of course, we will fight for it. But it is important that we are supported in the USA as well – there is a bad habit of adopting everything American, and if it goes in America, it will stimulate an increase in funding in Russia as well. Clinical trials of SkQ have already begun in the USA – I hope everything will be fine. The main market for medicines is America, 40% of all medicines are eaten by Americans. So far, our drops are sold only in Russia, but someone takes them out - buys them here in boxes and takes them out.
God and Gerontologists– Does the religiosity of society not hinder your studies?
I have heard from people more than once that God has determined how long we are supposed to live, and it is impossible to interfere in this.
– In the book I retell the conversation of my friend, President of the Gerontological Society of Russia Vladimir Anisimov with one of the exarchs of the Orthodox Church. They were traveling together on the train, and Anisimov asked the priest: "Can gerontology be considered a godly thing?" The priest did not immediately answer. I thought about it, shook my head and said, "If God permits, then you can." I always had a different answer – when my father has a toothache, he still goes to the dentist. Is it pleasing to God? Maybe God punished him with a toothache – let him suffer. Speaking out against life extension is like speaking out against antibiotics, because antibiotics have doubled people's lives.
– Are you an atheist?
– I am an atheist by upbringing, but it is more correct to say that I am an agnostic – I have no answer to this question. I will express one idea that brings me closer to religion. Here's the idea. Now the first artificial living beings have been created. Craig Venter took a bacterium and removed its own genes. There is a way – a substance is injected into the cell that disassembles the genes, nothing remains of them. Such a cell will live for some time, and then it will die without leaving offspring. And then they took a bacterium of another species, read its genes and artificially synthesized their analogues. The DNA obtained in this way was injected into a bacterium without genes, a semi-calm. And she, firstly, began to multiply, and secondly, she became that new bacterium - she completely forgot who she was. In fact, this is a precedent for the creation of a new living organism, albeit primitive. Although, what does primitive mean? A bacterium has about a thousand genes, it's not a virus with three genes. A real living being has been created, capable of reproducing and evolving.
This is what we already know how to do today. And progress in biology is fantastically fast, biologists themselves make mistakes in predictions all the time, underestimating the speed of change. I remember one of the largest biologists saying somewhere in 1980 that genes will learn to read no earlier than the end of the XXI century. And they learned – twenty years after this statement. Now in our laboratory your genome will be read in a month, it costs 25 thousand rubles. And soon it will be possible to do it much faster and cheaper. That is, the progress is enormous. And imagine that it's already the XXII century – will biologists in a hundred years not want to apply their talents to creating an artificial living world, where there will be not only bacteria, but a synthetic lion, a synthetic cow and many new species? They will create the whole world with their own hands – and then how will their activities differ from the works of the Lord God to create the world? Nothing.
– I can't imagine a more interesting entertainment than the creation of worlds. Aren't we already in such a world created by more intelligent beings?
– It is absolutely incomprehensible to me how some things in the living nature could have arisen by chance, without an initial plan. For example, the fact that a bacterium has a real electric motor is a discovery I made back in the seventies. You know, there are mobile bacteria that have a tail and they twist it.
– Flagellum?
– Flagellum. It starts from the difference in potentials on the membrane of the bacterium. The system seems to have been made by a person who had previously made an electric motor, the scheme is absolutely the same, right down to the rotor, reverse and other details. You can adjust the speed of rotation of the flagellum, change the direction of rotation. In general, I can't imagine how randomly thrown chips can form into an electric motor circuit, even in many steps. I know other such processes – for example, protein synthesis on the ribosome. I can't imagine how it could have arisen without a detailed plan developed by a very talented being.
– I wonder what will happen to a person in a hundred years? After all, we will be able not only to create other living beings, but also to change our genetic program.
– I think that by this time we will be able to rightfully call ourselves Homo sapiens liberatus – that is, a man not only intelligent, but also free, freed from the tyranny of his own genome, which orders us to live so little.
Portal "Eternal youth" http://vechnayamolodost.ru02.10.2014