Part 1: Can a person challenge their genes
In theory, living organisms can live for a very long time, almost forever. Where did such a bad property as death come from in living beings?
We will all die one day. Unfortunately (and maybe fortunately, there are different points of view), life is arranged in such a way that we get this miracle complete with a very unpleasant obligatory add-on - death.
Some biologists believe that this was not always the case. It seems that the famous August Weismann was the first to doubt the "inevitability" of death. This is the ancestor of the Weismanist-Morganist geneticists, so hated by Trofim Lysenko. In his lecture, which Weismann gave in Freiburg in 1881, he said: "I see death not as a primary necessity, but as something that is acquired a second time in the process of adaptation." So death was invented by nature specifically to ensure the change of generations, without which life cannot develop and without which evolution is impossible.
The role of DNA in heredity was not yet known. It was unclear how genetics was arranged in general, and Weisman felt that all this would be revealed: "There is no doubt that the higher organisms in the version of their design that has come down to us today contain the seeds of death." What seeds are we talking about? Of course, about genes. That is, if translated into a more modern language, a well-known biologist stated that death genes are embedded in all living organisms (that is, you and me). So it turns out that one day they can turn on and we will die right away. Let's commit, so to speak, molecular biological suicide.
How far have we agreed? To the point that living organisms are somehow programmed to commit suicide? It may seem crazy. Everyone knows about the instinct of self-preservation, and in general, what can be more valuable for the body and a person than his own life?
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The highest goal of a living organism
From a humanitarian point of view, that is, our human selfishness, of course, life is the highest value. But the author of these lines is a professional biologist, and even with a penchant for medicine. So I also consider a person as just a living creature belonging to vertebrates, animals, mammals, from the order of primates, the genus Homo, the species sapiens. And I know that for all living beings there is a thing that is much more valuable than their own life. This is the genome of their species. The set of all genes, which determines what this creature is, what kind of creature it is.
And this is a really important thing. The genome of each species has formed as a result of tens and hundreds of millions of years of evolution, and if it is once lost, the species will completely disappear, which means that all these millions of years have passed in vain. All living beings and in their number with you, from their parents receive a copy of the genome, check its (copy) performance during life, and if the copy turned out to be good, then it is passed on to their children. Someone else asks about the meaning of life? From the point of view of biology, it looks like this. I got it, used it a little and, if it works fine, I passed it on.
Usually, the interests of the genome coincide with the interests of its temporary carrier completely. If the creature, not having time to leave offspring, dies, then a copy of its genome will be forever lost. But sometimes very unpleasant situations happen when the wishes of the carrier himself do not coincide with the needs of the genome. And then our genes immediately show us who is the boss of the house.
A good example is brewer's yeast, one of the favorite subjects of research among biologists. (I suspect this is due to a wonderful by-product that they can produce.) Yeast is a rather primitive unicellular fungus, and it can live in two modes: reproducing asexually, or arranging sexual reproduction for itself.
If everything is fine in their life, then the yeast multiplies, spitting off new cells from itself, its exact copies-clones. The process can be repeated many times, and the yeast lives for a very long time, multiplying in number and trying to capture as much space as possible. Evolution in this mode is extremely slow, because the variability is very small, new and old cells are mixed in the environment, and there are a lot of old ones. In general, stagnation.
But then the conditions begin to deteriorate (for example, all the simple food that is in the area has been eaten). Yeast cells feel that the freebie is over and "decide" to accelerate their own evolution, regaining the ability to quickly adapt to new conditions. This is done using two things:
Mandatory sexual reproduction is introduced.
To do this, yeast cells agree on which of them will be a boy and which will be a girl, and arrange a gene exchange.
Rapid death appears.
Programmed death of yeast cells, which is absent in more comfortable conditions of asexual reproduction. It is obviously necessary in order for the old yeast generation to make room for the new one resulting from the "shuffling" of genes.
And you know what is the signal that triggers the programmed death of yeast cells? Pheromone - a substance that the yeast of one sex senses the representatives of the opposite sex. The discovery of this fact caused a lot of noise in the crowd of yeast scientists. Here is such a heartbreaking story of love and death in brewer's yeast.
Sacrifice is a general rule
That is, as soon as the species needed to accelerate its own evolution, the interests of individual individuals were immediately sacrificed for the sake of His Majesty Genome. And this rule, sad for individual individuals, can be traced on creatures of any complexity.
Think of the annuals that die as soon as their fruit ripens. By the way, they may not be annual at all. Just breeding once. For example, bamboo lives for decades, and then blooms, forms seeds and then dies. Note that a couple of mutations in the genes of an annual plant can turn it into … a perennial. For example, Belgian geneticists managed to do this, the work was awarded publication in Nature.
Do you think this only applies to mushrooms and plants? Here are the insects. The crown of evolution, by the way! Ask any invertebrate zoologist who is cooler - dipterans or some clumsy bald monkeys? Mayflies do not live long: from a couple of hours to a couple of days (depending on the specific species), because they have no … mouth. They cannot eat and die of hunger. Does every single mayfly like it? I don’t think so. Are they happy with the genome of their species? I'm sure. Simply because it is a very successful, that is, a widespread and very long-standing animal species. Much older than you and me.
Break the system, change the program
So, oddly enough, there are suicidal genetic programs. But we started talking about them not at all in order to once again amaze at the arrangement of living nature. There is a much more pressing question that concerns each of us. Remember - "we are all going to die"? Doesn't our genome have something to do with this sad fact? Have we not inherited from our primitive ancestors some genetic program, the purpose of which is to bring us to the grave?
I will try to prove to you that it is so. And we can quite afford to break this program. Because it is needed for the sole purpose of accelerating the evolution of man as a biological species. But we no longer need this, because instead of a snail's pace of evolution, humans have long been using a much faster and more effective method of survival as a species - technical progress. This means that he no longer needs all kinds of unpleasant evolutionary tools and they can be turned off, no matter how His Majesty the Human Genome protested against this.
In other words, it is quite possible to pose the question, do we want to continue to be a temporary repository of genes on the way from one generation to the next? A biological machine, blindly following the orders of its own genome? Is it time for a machine uprising?
Part 2: How the genetic program drives people to the grave
The greatest threat to humans is biological aging, that is, the slow weakening of the body's functions, which inexorably increases the likelihood of death. There is every reason to believe that aging is the result of a genetic program.
With all the greatness of Mankind and Man, you and I are nothing more than biological machines. Our parents uploaded a program into us - our life, our genome - the execution, in fact, of this program. What is it? The fact that we need to develop in the form of an embryo, be born, grow up and, if the downloaded copy of the genome was successful in us, transfer this copy to our children. But the program doesn't end there. Because there is also a final stage in it - it is necessary to free up a place in the cave for the next generation, in other words, to die.
If everyone agrees with the first stages of the program, then somehow they don't like thinking about the last part. And not only ordinary people, but also professional scientists. Maybe this is because most biologists are very fond of life and in all its manifestations. Actually, that's why we became biologists. It is always much more interesting for us to explore where something comes from, than where it goes later, how it is destroyed.
In this regard, the history of the study of proteins is very instructive (their other name is proteins, this is specifically what is encoded in our genes, the most important part in any living system). The process of protein synthesis in cells began to be studied closely as early as the 50s and very quickly figured out how this happens. Since the 70s, all textbooks have described the corresponding mechanism, which works perfectly and all the time produces all the proteins we need. Question: where do they go then? They don't live forever. The cell would simply burst from all the time synthesized proteins. But for some reason, biologists somehow "did not bother much with this issue." And overlooked a large and complex system of protein degradation. It occupies more than 10% of all our genes, and which determines exactly how long a particular protein should live,depending on its function. Some of them live only a few hours, others remain in the cage for years. They began to wash about this only in the late 80s, and the Nobel Prize was awarded for the discovery of a system for the targeted destruction of proteins.
Spoil the program
Didn't a similar story happen with the programmed death of the organism? Maybe biologists didn't want to just think about it? And in vain! Because if our death is also programmed, like our birth, then this gives us a huge chance to live better and longer. The fact is that biology, with all its achievements, is a fairly young science. We still know quite approximately how living nature is arranged and still do not know how to create various new biological systems that could be useful to us to extend our own life. But if our death happens due to the action of the program, then there is no need to build anything. On the contrary, it is necessary to break. Break the last stage of this program, which is fatal for us. Moreover, it is even possible not to completely break it (this can be dangerous, and, probably, it is still impossible),it is quite simple to interfere with it somehow, to insert this mechanism into the wheels of sticks. For all the youth of biological engineering and biology, we somehow already know how to break. And then the mechanism will work worse, which means that we will live longer.
And yet, is there a similar mechanism of programmed suicide in the human body? Perhaps the scientists somehow overlooked it, just because it is not there, and not because they did not want to look? With all due respect to my colleagues, I don't think so. And then I will try to prove how it is possible in general in such a lax science as biology, that yes, we have this program. And you can quite start to fight it. But in order to find out what this is about, you will need to read this series of articles to the end.
Well, what kind of program can we talk about? There are several options, and let's start with the simplest. There is a very nasty and deadly thing like sepsis. It usually happens when the blood gets infected with bacteria. That is, if a large number of microbes get into the blood, it is very dangerous. A person's temperature rises sharply, the so-called systemic inflammation develops, and the process most likely ends in the most sad way - the patient dies. By the way, this also works on other animals - rats, mice and any other animals.
Why does this happen? It would seem that everything is clear. Bacteria began to multiply in the blood, the immune system cannot cope with them and they "eat" the human body from the inside. And what, one wonders, might not suit us with such a straightforward and understandable explanation?
Deadly immunity
But here's the problem. At some point it turned out that the same effect can be achieved (not in humans, of course, but in an experiment on rats) if dead (!) Bacteria are introduced into the blood. They can neither reproduce, nor "eat" anything. And the symptoms are the same - fever and inflammation, and as a result, death from multiple organ failure. Aha! - said the interested scientists, - it means that bacteria are not terrible in themselves, but because they contain some very poisonous substance for humans (or mice)! It also causes septic shock. They began to understand and really isolated such a substance from bacteria, or rather from their shells. If it is cleaned and introduced into the blood of an animal, then the unfortunate creature will likewise die from septic shock. What is this substance? What a terrible bacterial poisonwhich was immediately called endotoxin - that is, the internal poison of bacteria?
It turned out that this is a simple polymer consisting of residues of sugars and lipids - lipopolysaccharide (English abbreviation - LPS). In its chemical essence, the substance is completely harmless, it is just a building material that makes up the cell wall of bacteria. How can LPS be toxic to mammals? They began to understand further and found out that mammals have special proteins - LPS receptors, which constantly monitor the blood for the appearance of this substance. And if they detect a certain amount of LPS, then they trigger a terrible cascade of biological reactions, which we call septic shock. If we make a mutant mouse that has a broken gene for this receptor, then for such a GMO mouse the most lethal dose of LPS will be absolutely harmless.
Her body simply will not notice the "endotoxin" and will continue to live happily on. You can break this suicidal program in another way. The eerie inflammatory cascade in response to LPS is part of the body's immune system. We know of substances like corticosteroids like dexamethasone that are good at suppressing the immune system. Accordingly, if LPS is injected into a mouse together with dexametozone, the mouse LPS receptors, of course, will detect and transmit a signal “upward” to the immune system. But this will not lead to anything terrible, because it will be disabled. And the mouse will survive.
In general, if we omit all these terrible details, then the conclusion is the following: death from septic shock occurs as a result of the work of a special suicidal program. The body kills itself if it finds inside itself a sufficiently large number of pathogenic bacteria. By now, a lot is known about this program: how it starts, which parts of the immune system it activates, how and when the process enters an irreversible phase.
Sacrifice for the rest
A reasonable question arises, but very unloved by biologists: why? Why did mammals have this lethal system? It is definitely not needed by a separate organism. Without the septic shock system, he would have at least some chance of "crushing" the infection and surviving. But nature does not give this chance, finishing off the unfortunate, and even if the bacteria that infected him are already dead. Why?
An exact answer to this question, of course, cannot be given, for the paths of evolution are inscrutable … well, or the one who directs it there. But, actually, this whole story looks very reasonable and practical. True, not from the point of view of an individual person, as the crown of nature, but from the point of view of His Majesty the Genome of Homo sapiens.
In primitive times, which by evolutionary standards were only a few seconds ago, an infected individual was extremely dangerous to the rest of his species. Because he could transmit the infection to them, infect the entire population and … what if this is the last population of this species? Then he (the species) will disappear, and with it his genome. Worse, even if the disease is not fatal, it is still very dangerous. The fact is that at the initial stages, the body fights infection by synthesizing very toxic substances - free radicals (I will talk about them in one of the following columns).
These substances are mutagenic. And if the infection was severe, then a lot of radicals are synthesized, and this is already a direct threat to the appearance of too many mutations in the genome. Well, how will a diseased individual survive and, with all its mutations, give birth to children with non-understandable genomes? Dangerous! From the point of view of the species and, most importantly, its genome, it is much preferable if the infected individual does not run anywhere, lies quietly under the nearest bush and … dies without infecting relatives and no longer participating in reproduction. This is the goal of the septic shock program.
But in the modern world, a person does not need such a program at all. Because we have antiseptics and antibiotics.
And about old age
Well, well, the gallant reader who has held out to these lines will say, let's say sepsis is a program. But fortunately, septic shock is far from the main cause of death in people. There are others that are much more common. And what do they have to do with programs, genomes and the uprising of biological machines?
The answer is: do you know what is the most common cause of death? Threatening 100% of people over, say, 20 years old? This is biological aging! That is, a slow and consistent weakening of body functions with age, inexorably increasing the likelihood of death. So, the author belongs to those biologists who believe that we have every reason to consider aging as the result of the activity of such a genetic program. And in the next issue of our bio-series, I will try to present you with evidence of this bold hypothesis, and naked evolutionary champions will help me in this.