The biggest threat to humans is biological aging, that is, the slow decline of bodily functions, inexorably increasing the likelihood of death. There is every reason to believe that aging is the result of a genetic programIn the previous episode of my heartbreaking, I hope, series about love, death and the tyranny of the genome, I tried to draw the attention of dear readers to the fact that for all the greatness of Man and Humanity, you and I are nothing more than biological machines. Our parents have uploaded a program into us—our genome, our lives—in essence, the fulfillment of that program. What does it consist of? It is that we need to develop as an embryo, be born, grow up and, if the copy of the genome uploaded to us was successful, pass this copy on to our children. But the program doesn't end there. Because there is also a final stage in it – you need to make room in the cave for the next generation, that is, to die.

If everyone agrees with the first stages of the program, then they don't really like to think about the last part. And not only ordinary people, but also professional scientists. Perhaps it's because most biologists are terribly fond of life, in all its forms. In fact, that's why we became biologists. It is always much more interesting for us to study where something comes from, than where it then goes, how it is destroyed.

In this regard, the history of the study of proteins (their other name is proteins, this is exactly what is encoded in our genes, the most important part of any living system) is very instructive. The process of protein synthesis in cells began to be closely studied in the 50s and it was quickly figured out how it happens. Since the 1970s, all textbooks have described a mechanism that works perfectly and constantly produces all the proteins we need. The question is: where do they go then? They don't live forever. The cell would simply burst from the constantly synthesized proteins. But for some reason, biologists somehow did not "bother" with this issue. And they overlooked a huge and complex system of protein degradation. It occupies more than 10% of all our genes, and it determines exactly how long a particular protein should live, depending on its function. Some of them live only a few hours, others persist in the cage for years. It was only in the late 1980s that people started thinking about it, and the Nobel Prize was awarded for the discovery of a system for the pinpoint destruction of proteins.

Mess up the program
Didn't the same thing happen with the programmed death of the organism? Maybe biologists just didn't want to think about it? But in vain! Because if our passing away is as programmed as our birth, then it gives us a tremendous chance to live longer and better. The fact is that for all its achievements, biology is a very young science. We still know very roughly how living nature works, and we are not yet able to create any new biological systems that we might need to extend our lives. But if our death is due to the action of the program, then there is no need to build anything. On the contrary, it is necessary to break it. To break the last stage of this program, which is lethal for us. And you don't even have to break it completely (it can be dangerous, and probably not yet possible), it is enough just to somehow interfere with it, to put spokes in the wheels of this mechanism. For all the youth of biology and biological engineering, we already know how to break something. And then the mechanism will work worse, which means that we will live longer.

And yet, is such a mechanism of programmed suicide embedded in the human body? Maybe scientists overlooked it simply because it doesn't exist, and not because they didn't want to look for it? With all due respect to my colleagues, I don't think so. And then I will try to prove, as far as this is possible in such a relaxed science as biology, that yes, we have this program. And it is quite possible to start fighting it. But to find out what all the fuss is about, you'll have to read my bioengineered series to the end.

 
So, what kind of program can we talk about? There are several options, and let's start with the simplest one. There is such an unpleasant and deadly thing as sepsis. It usually occurs when the blood is poisoned by bacteria. That is, if a sufficient number of microbes got into the blood, it is extremely dangerous. A person's temperature jumps, the so-called systemic inflammation develops, the process is likely to end in the saddest way - the patient dies. By the way, it works in the same way on other animals – mice, rats, any animals.

Why is this happening? 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 how can we not be satisfied with such a direct and understandable explanation?

Lethal Immunity
But here's the problem. At some point, it turned out that the same effect could be achieved (not on humans, of course, but in an experiment on mice) if dead (!) bacteria were injected into the blood. They can neither reproduce nor "eat" anything. And the symptoms are the same – fever, inflammation, death from multiple organ failure. Aha! Bacteria are terrible not in themselves, but because they contain some substance that is very poisonous to humans (or mice)! It causes septic shock. They began to sort it out and really isolated such a substance from bacteria, or rather from their shells. If it is purified and injected into the blood of an animal, the unfortunate creature dies of septic shock in the same way. What is this substance? What is this terrible bacterial poison that was immediately called endotoxin – that is, the internal poison of bacteria?

 
It turned out to be a simple polymer consisting of residues of sugars and lipids – lipopolysaccharide (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 Poisonous To Mammals? We began to look further and found out that mammals have special proteins called LPS receptors, which constantly monitor the blood for the appearance of this substance. And if they detect a certain amount of LPS, they trigger a terrible cascade of biological reactions, which we call septic shock. If you 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 completely harmless.

Her body will simply not notice the "endotoxin" and will continue to live happily. There is another way to break this suicidal program. The terrible inflammatory cascade in response to LPS is part of the body's immune system. We know of substances, such as corticosteroids like dexamethasone, that are good at suppressing the immune system. Accordingly, if LPS is injected into a mouse along with dexamethosone, then the mouse LPS receptors, of course, will detect and transmit a signal "upwards" to the immune system. But it won't 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 as follows: death from septic shock occurs as a result of the work of a special suicidal program. The body kills itself if it finds a sufficiently large number of pathogenic bacteria inside it. By now, a lot is known about this program: how it is triggered, what parts of the immune system it activates, how and when the process enters an irreversible phase.

Sacrifice for the sake of others
A reasonable, but very disliked question by biologists arises: why? Why did mammals have this lethal system? An individual organism definitely does not need it. Without the septic shock system, he would have had at least some chance of "crushing" the infection and surviving. But nature does not give this chance, finishing off the unfortunate person, even if the bacteria that infected him are already dead. Why?

Of course, it is impossible to give an exact answer to this question, because the paths of evolution are inscrutable. Or whoever directs it there. But, in fact, this whole story looks very reasonable and practical. True, not from the point of view of the individual man, 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 it (the species) will disappear, and with it its genome. Even worse, even if the disease is not fatal, it is still very dangerous. The fact is that in the initial stages, the body fights infection by synthesizing very poisonous substances – free radicals (I will talk about them in one of the next columns).

These substances have mutagenic activity. 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. And how will a sick individual survive and, with all its mutations, give birth to children with incomprehensible genomes? Dangerously! 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... will die without infecting its relatives or participating in reproduction. This is the purpose 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, the valiant reader who has lasted up to these lines will say, let's say sepsis is a program. But, fortunately, septic shock is far from the main cause of death. There are others that are much more common. And what do they have to do with programs, genomes, and the rise of biological machines?