What is cryonics and whether it is possible to find immortality in liquid nitrogen

It took more than fifty years since the day when the first California cryopreserved human body by cooling it to a temperature below -70 degrees Celsius. This man was James Bedford, Professor of psychology at the University of California. Bedford, a terminally ill cancer responded to the offer Cryonics Society of California, which promised free frozen body of the first volunteer after his death. Since then, Bedford's body is in a state of chilled in liquid nitrogen in the expectation that science will develop so that he could give him another chance at life.

Over the past since '51 cryonics has evolved significantly and even turned into a business, and the expense of frozen people waiting for the resurrection, has been going on for many tens.

Imagine that you have a favorite grandmother, who recently feels very good. Grandmother heavy hereditary disease caused by a well-known medical single mutation. Although the mechanism of occurrence and development of the disease is known to almost all our imperfect treat her medicine until you know how. So, regularly bumping on news

genomic editingOf DNA vaccines and the success of the first CRISPR / Cas9 system testing, you realize that even just some 20-30 years, and your grandmother could have received a short course of DNA therapy to recover. However, as we originally agreed, grandmother feels bad today and no in 20-30 years you have no reserve.

Obviously, the most logical way out would be to somehow gain time, "freezing" of the disease. For example, freeze grandmother literally - her body can store up to better times in the liquid nitrogen with the expectation that in the future any disease, no matter how difficult it may be, physicians will be able to cure. Make freeze when life is impossible in law (and grandmother against), but we can already order that after ascertaining the fact of death, the body has been preserved for the future as soon as possible.

Companies that offer such services already exists. And not only somewhere in the US, but also, for example, here we have at hand, in the suburbs. The company "KrioRus" vault which is located in Sergiyev Posad, has been doing this for many years and for some 36 thousand dollars is ready to provide permanent storage of the body. If it will seem expensive, for ridiculous 15 thousand dollars can be saved separately the head or brain. In addition, the company is ready to provide its customers with even installments or annual subscription. Agree, it would be strange not to take advantage of this affordable service, especially since the only alternative in this case - is the death, burial and final dissolution.

In the example of a hypothetical grandmother this decision does seem the most logical and simple. And many people are faced with this dilemma is not hypothetical, but quite real, dare to take this step. Today, they already account goes on hundreds of people.

The problem is that not every decision that seems logical and simple, in fact, true.

There are no guarantees and reverse - that attempts to save lives at low temperatures are doomed to failure, and are engaged in this, they say, only crooks. Life is much more complicated this scheme, but in order to understand where this story is the border between science and charlatanism, it will take quite a long story.

Physicist Michio Kaku succinctly but convincingly explain cryonics problems in its present form.

There's a starman waiting in the sky

In the summer of 1931 Rob Ettinger was 12 years old. It was the time of the peak of the Great Depression, and especially acute economic downturn was felt in Detroit, where Rob while he lived with his family (by the way, came from Russia). Like many of his peers, the boy was fond of science fiction, and its main source at the time were illustrated magazines like "amazing story» (Amazing Stories), which published such classics like Jules Verne and HG Wells. And here, in the issue of "Amazing Stories" for July 1931 Rob came across the story of "Sputnik Jameson, "the author of which was important for the history of the genre, though not well known today, the author of science fiction Neil Jones.

The plot of the story was this: one Professor Jameson (something like Elon Musk 1930) sends your body into Earth orbit with the expectation that in the cosmos, at temperature close to absolute zero, it becomes an independent satellite of our planet, and will remain intact indefinitely (we recently We have seen likeOnly with a dummy instead of the body).

In the story of what happens: after millions of years of people-race mechanical cyborgs Jameson finds the body in orbit, its brain reanimate, connected to a robotic "skeleton", and a former professor becomes a full member of the alien society future.

The story made a lasting impression on Oettinger, and the thought of the possibility of indefinite storage of the body at a low temperature followed him the rest of his life. A few years later these experiences overlap news about the work of French biologist and philosopher Jean Rostand, who one of the first learned to preserve biomaterials viable sub-zero temperatures - Frenchman worked with sperm frogs.

In 1947, impressed by his achievements Ettinger wrote a story called The Penultimate Trump, in which the idea of ​​cryonics was first developed in the most vivid detail. In the opinion of Rob, this technology should become a sort of one-way time machine, with which it will be possible deliver terminally ill patients in the bright future of high-tech medicine and thus ensure unlimited longevity person.

The story was published in the science fiction magazine Startling Stories, and after a decade and a half roughly the same ideas, but in a non-fikshen format Oettinger outlined in his opus magnum, the book "Perspective immortality. "

Followed by the publication of the struggle for recognition, the first supporters education cryonics society and, finally, the first real freeze. Oettinger has lived a fairly long life, has seen ups and downs of the movement founded by him and died only in 2011, at the age of 92 years. As you can imagine, his body was frozen in liquid nitrogen: cryonics father became the 106th "Patient» Cryonics Institute.

Company founder Alcor Mack Moore conducts a tour of his cryostorages - the largest in the world today.

Song without flame ice

Oettinger's ideas became the core of the movement, which is now called transhumanism. Cryonics in it side by side with cyborgization, propaganda of radical life extension, is now fashionable biohakingom and other cyberpunk. Depending on the personal temperament and educational backgrounds of these transhumanist ideas can mutate into a more or less radical forms, ranging from quite realistic (like growingfarmers bodies artificial organs) to completely zaviralnye (such as the relocation of consciousness to the Internet).

Tell the story of all this movement in one text would be impossible, and even the very practical aspect of cryonics, amazing stories establishment of companies and Alcor "KrioRus' stories and experiences of their clients and critics, the scandals with the bankruptcy and the loss of Alcor bodies" cryonics "- all the entourage that has accumulated around the cryonics for several decades, is described in such detail that spoil others' stories would be retelling meaningless.

So let us for a moment leave aside the scandals and intrigues, take freezing services existence as a reality and We try to deal with how, in principle, the noble goals of cryonics are achievable, and used her methods are adequate tasks. For this we need to delve into it, the behavior of water, cells and living tissue at low temperatures.

The basic premise of the existence of cryonics is the fact that at temperatures close to absolute zero, chemical processes are slowed down dramatically, and It means while to stop for a living tissue, which allows to fix the state of the system until the moment when we decide that it is necessary do.

The reasonableness of this approach has been noticed even in the (good old) van't Hoff rule, according to which "at the temperature is lowered for every 10 degrees constant homogeneous elementary reaction rate decreases 2-4 times. " For biological tissue, which, for example, cooled to 37 ° C to the boiling point of liquid nitrogen, this means a retardation of processes at least 13 orders of magnitude (223), and the enzyme reaction, which for biological systems are much more important, the speed of the fall will be more more.

If we talk only about the current slowing of reactions, particularly on the point of storage, there is no problem in cryonics not. This is recognized even her staunchest critics. The problems arise in all other places.

To reach the temperature of liquid nitrogen, the body must first be cooled. Thus there is a plurality of complex effects. For example, the cell membranes lose their elasticity, as proteins, designed to operate at ambient temperature, can begin to denature. And then, and more - important things that can nullify the efforts to preserve the viability of the cells, but their impact pales before the problem of ice crystals.

The detailed mechanism of the water of crystallization is not as simple as it might seem: it has been well studied for the case of pure water (although there is only one phase in the ice known 17 pieces), however, in addition to the H₂About, in the tissues there are salts and proteins, and sugars, and semi-permeable membranes, and many other things.

The cause of ice is thermodynamically favored at the process temperature falls below a certain threshold. The presence of salts in the water, sugar and other substances may reduce this threshold, but this dependence is too difficult: for example, a salt of NaCl can maintain liquid water exactly to -21.4 degrees Celsius, whereupon a further increase of its concentration, by contrast, leads to a sharp increase in the threshold up to room temperature.

More important to remember that by itself "the profitability of the process" does not imply its immediate implementation of thermodynamics only controls the direction of the reaction, but not its speed. And this rate is, of course, itself depends on the temperature.

The chart can be seen the freezing point of sodium chloride in water solution at different salt concentrations. At the lowest point, at a temperature of -21.4 degrees Celsius NaCl fraction is 24 percent by weight. The concentration is given in molar units.

Let's take a concrete example. What usually happens with raspberries that you want to freeze in the winter in the freezer? Usually obtained externally beautiful, hard berries that after defrosting turn into mush varying degrees of homogeneity. This occurs because cells in the form of ice crystals that disrupt membrane integrity, and follows the contents into the extracellular space. If frozen in ice cages appeared, then bring the situation back and save the cells have no chance.

Some particularly radical advocates of cryonics is believed that there may come to the aid of the distant future nanorobots that will be able atomwise repair damaged cells. Such fantasy is better to read the original (for example, hereThe technical feasibility of cryonics), Constantly comparing the statements of the authors with the ability of real-life nanorobots (suchCellular Cargo Delivery: Toward Assisted Fertilization by Sperm-Carrying Micromotors), And to draw conclusions on their own.

If the occurrence of intracellular ice crystals - this instant judgment, it may be, this process can be prevented by making the procedure for freezing smoother? Indeed, intra- and extracellular space is strongly characterized by their volume and structure, therefore, occurrence of ice nucleation points significantly more likely it is in the intercellular space. When initiating cooling of the system (i.e., near the melting temperature) of the ice formation rate is limited number of nucleation points, so a sufficiently slow cooling with ice advantageously occurs outside, rather than inside cells.

This is potentially a much more favorable situation, but there is one "but": the ice does not stand in its structure almost no impurities, and therefore all salts sahará intercellular medium during crystallization are pushed out into the liquid phase. Because of this, the osmotic pressure in the tissue is increased tenfold and the cells are subjected to actually slow mummification in brine (this is shown clearly in experiments where instead of exposure to cold cells are simply placed in a salt solution whose concentration corresponds to a given temperature, - the result in both cases perfectly match).

The graph below - the proportion of killed erythrocytes (hemolysis levels) in the two experiments. In the first freezing conducted in the second - just incubation in saline. In the latter case, the concentration of the solution corresponds to the osmotic pressure in the liquid phase frozen blood obtained on the basis of calculations.

So, by slow cooling cells are not torn as in fast, but on the contrary, dry up. But this is unlikely to please the supporters of cryonics: it turns out that by adjusting the cooling rate, it is possible to control only the cause of cell death, rather than eliminate it itself.

Below the graphs the survival of different cell types at different rates of cooling: it is seen that even in the case of primitive unicellular yeasts is the optimal cooling rate leads to the fact that half of the cell is irreversibly perishes. This is not a problem for the yeast, in which a single cell is sufficient to recover the strain. But what would happen if (putting tremendous efforts) someone will be able to achieve a similar level of cell survival during cryopreservation of human? As a maximum, you have on hand will be not the corpse, but only semi-corpses.

The following graph - survival ratio after freeze / thawing cells in the sample depending on the cooling rate. For all the samples - both yeast and animal cell lines - there is only one point of optimal cooling rates and survival in it is far from 100 percent.

Time is up

It turns out that to maintain the cells alive when frozen is quite impossible, and the work of all these cryonics companies - this is pure fraud?

Regarding the second part of this statement, the majority of scientists believe something like this. But here's the first part is actually incorrect, otherwise there would be no sense in all this talk.

Experiments on the conservation of living cells and tissues at low temperatures are maintained, and quite successfully, but their actual results are still very far from these ambitious objectives that cryonics company like a long time ago We decided.

It should make one terminological distinction. If cryonics - it goes back to Ettinger the idea of ​​preserving human bodies for future revitalization and treatment, the development of methods preservation of cells and tissues at low temperature is called cryopreservation (cryopreservation), and any related science - Cryobiology. A significant part of specialists in this field - it embryologists, who are constantly improving methods of freezing and thawing of semen, ova and embryos and even the genital tissues.

Scientists are constantly trying to adapt existing cryopreservation techniques for increasingly large and complex bodies. Already mastered the blood vessels, cartilage and cornea, animal experiments are carried out with the kidneys and ovaries. But the transfer of the human body is entirely produced now - it's like to sell the land on exoplanets Trappist systemSeven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1: You can, of course, but do not be surprised if you will be considered a rogue.

How can I preserve the viability of the cells during freezing, if, as we have already established, nor high nor low, the cooling rate is not able to prevent the formation of ice?

The hope is that it's still possible, is behind the term "vitrification" (from the Latin root vitrum - "glass").

Vitrification or glazing, involves obtaining a volatile substance in an amorphous state, wherein formation of ice crystals at low temperature is still thermodynamically favorable, but does not occur at kinetic reasons.

Vitrification is possible to achieve in the case of crystal growth rate is not kept pace with the increase in viscosity occurring at lower temperatures. The fact that the crystal growth is necessary for the movement of water molecules to the front of crystal growth and the speed of this process depends on the viscosity. If you add the substance solution, which increases the viscosity, molecular motion will be nearly unstoppable, and with it, and stop the growth of crystals. The system as it freezes, and reaching more energetically favorable state.

Vitrification - is not a magic wand that allows magical way to circumvent the prohibitions physics. In terms of cryopreservation practice it has its "dark" side. First, it requires a very large, just the same, huge concentrations of cryoprotectant - substances to increase the viscosity of the medium. We are talking about such concentrations, when the fabric is actually half of this "anti-freeze", and only the other half - from the water. And because almost all substances in these concentrations are toxic, scientists again faced with the dilemma of death or death of ice from ice control.

The graph below shows the behavior of the solution of glycerol (cryoprotectant historically first) with slow cooling. In the phase diagram water Tm indicates the temperature of crystallization at a given glycerol concentration, Tg - temperature vitrification solution. The arrow shows the concentration of glycerol and the temperature of the liquid phase system.

It can be seen that the initial cooling leads to an unstable state where ice crystals have not formed and the concentration of glycerol in the remaining solution is constant. Then the concentration begins to rise, exactly following the Tm up until a certain point, the cooling rate does not advance the crystal growth rate and the system does not overcome the threshold vitrification Tg. In larger cooling rate this inflection occurs earlier.

Secondly, few successfully achieve vitrification temperature - the point where the fabric is actually transformed into glass.

More necessary and figure out how to return from this state back to room temperature.

The problem is that during cooling, flows downwardly through the glazing threshold, the total amount of ice limited by the rate of growth of existing crystals, but the avalanche new form nucleation centers. When moving in the opposite direction, i.e. heating, these centers already exist, and the crystal growth rate is accelerated while each degree up to the melting temperature.

All this leads to the fact that the critical heating rate of vitrified tissue is always several orders of magnitude (sometimes in the hundreds of thousands of times) higher than the critical cooling rate. Therefore, in recent years a lot of attention in this area is on innovative methods of heating, not cooling. Among the optionsImproved tissue cryopreservation using inductive heating of magnetic nanoparticles - the use of induction heating or radio previously entered into the tissue of the ferromagnetic particles.

The real state of affairs is best in this area describes an example of the work of Greg Fahy - one of the most renowned experts in Cryobiology (which, as far as can be judged, generally quite sympathetic to the ideas of transhumanism that for biologists rarity). Fahy Group for several years trying to learn how to freeze and thaw the kidneys of rabbits so that they retain their physiological function.

The purpose of this work is clear: according to statistics, up to 60 percent of the bodies that can be used in transplantation, end their lives in the trash - and this despite the fact that the authorities are queues for many thousands of people. It is estimated that if half of these bodies has been used for its intended purpose, the queue for transplantation for a couple of years would disappear as a phenomenon.

The problem is that even in a chilled state, the maximum survival time of donor organs is measured in hours: 36 hours for a more long-renal, and 4 hours for the heart and lungs. During this time, it is very difficult to find the right recipient and quickly organize transplant. Creating a bank of frozen bodies could solve this problem, but the technical complexity of this task has not yet been overcome. For example, according to Fahey, even a small change in protocol cooling can have a dramatic impact on the results, making the selection of parameters for each body is very complex.

Several years ago, the group was able to reduce the formation of ice when vitrified a rabbit kidney to 6 percent of body weight and to prove its viability. But even such seemingly small amount of ice destroys the circulatory system of the body and reduces the practical benefit of transplantation at no. It is worth only half as much time to increase organ perfusion, and the formation of crystals stops - but kidney cells while dramatically cease to withstand the toxic effects of cryoprotectant and perish.

It turns out that even in the case of one particular body between life and death are some extra 15 minutes of perfusion, some subtleties of the procedure. You can imagine how delicate, complex and long-term optimization would need if we were to try to do the same with the human body in its entirety. Not surprisingly, the commercial companies involved in cryonics, prefer to talk about the kind of work nanorobots and inevitable technological singularity.

conclusion

Of course, if you look at the problem of Cryonics wider, nothing is impossible in principle in it. Tardigrades, beetles cucujidae, Siberian salamander and many frogs, being aware of the history of this question, just laugh of human problems: they long ago learned to withstand deep freeze without any significant consequences. Some of them have to do yourself is synthesized in your body cryoprotectant such as glycerol or glucose, others have decided to ice the problem dramatically - almost completely got rid of the water in his body.

But what can you do - the person does not Tardigrada. Fortunately, we have a brain, and therefore, in some point, through the development of technology and the progress of Cryobiology we still can a little closer to her brilliant perfection.

Judging by the pace of real achievements, now living people of this bright future is not will catch.

And while we're just moving in this direction, it is best to be guided by the words of science popularizer, the founder of the journal "The Skeptic" Michael Shermer, said just about cryonics: "The problem in the study boundaries possibilities of science is reduced to finding a balance between, on the one hand, opening up a new, down to the acceptance of radical ideas, but on the other hand, the limitations of this openness, so that your brain is not dropped or lost finally".

Literature

Popular reports on the practice of cryonics

• Inside the weird world of cryonics - Financial Times report on the practice of cryonics in the United States and Russia (18.12.2015).
• «ice immortality"- a report by RBC COMPANY" KrioRus "(02/19/2014).
• «Salto in immortale"- Svetlana Reuters report about the Russian Transhumanist movement (Lenta.ru, 14.01.2014).

scientific work

• Cryopreservation and Freeze-Drying Protocols. Methods in Molecular Biology / Ed. by Wolkers, Willem F., Oldenhof, Harriette. - Hannover: Humana Press, 2015. The current guidance on cryopreservation techniques, vitrification and sublimation. Extensive introductory part of the book describes the physical and biological bases of behavior of tissues during freezing. The third edition can be seen here.
• The promise of organ and tissue preservation to transform medicine / Giva, S. Et al. - Nature Biotechnology, 2017. Overview of problems preserving the viability of organs in transplantation and existing technologies to solve them. Article allow us to understand the context in which the development of medicine could lead to the creation of evidence-based cryonics.
• Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification. EXAMPLE current state cryopreservation methods in the case of one specific organ - kidneys. Work group Fahy made on rabbit kidney, with extrapolation from modeling on the human kidney.