24 February 2016

Suspended animation I

Minimum life

Azamat Akkizov, "Biomolecule" 

We are used to the idea that life is a process that is interrupted once and for all. However, literally before our eyes, the boundaries of everyday phenomena are rapidly expanding. Scientific and technological progress competes with our imagination. And of course the question arises: is life necessarily a continuous process?

The main question

The idea of living forever transformed into the idea of living for a very, very long time. And not just for a long time, but staying in the prime of their powers and capabilities. Therefore, the question of "eternal life" did not disappear, but only began to sound more scientific: is it possible to slow down aging or stop it altogether?!

Can.

This encouraging answer, based on a serious scientific foundation, promises rosy (not to say fantastic) prospects.

Micro - resolution

The problem of a long and fulfilling life is as old as the world. The history of the search for overcoming it is lost in the darkness of centuries. However, the scientific approach to solving this problem has its own "birthday".

Formally, it all began on September 1, 1701, when the famous Dutch microscopist Anthony van Leeuwenhoek put some wet sand taken from a lead gutter from the roof of his house in Delft into a glass tube with water and began to examine it with a homemade microscope. A little later he will write about the results of his observations to the Royal Society of London. The letter entitled "About some Animalcules (literally – animals) found in the sediments of the gutters of the roofs of houses" contains a description of drying and "reviving" in the water of a strange kind of microscopic animals (Fig. 1).

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Figure 1. Leeuwenhoek made the best lenses for his time and masterfully sketched and described the "animals" seen through them: "A small insect that lay dry for 21 months, put in water and began to swim, attach its rear end (V) and extend its wheels (WX)" (a). Presumably, it was about the rotifers of the genus Philodina now known to every naturalist (b). Drawings from [1] and from the site aquaplantfish.ru .

In this letter, Leeuwenhoek shares an assumption that was very bold for enlightened Europe at the beginning of the XVIII century: "If these Animalcules, after being in a dry state for such a long time, are able to straighten out and move in the water again in the usual way, then we can conclude that in many places where the water stagnates in summer and then dries up, there may be many species of Animalcules that originally did not live there, but were brought there (from other places) on the paws and feathers of waterfowl ..." [2, 3].

Leeuwenhoek's contemporaries, of course, safely consigned his discovery to oblivion. At first glance, this was facilitated by a completely objective circumstance: Leeuwenhoek used exceptionally strong homemade microscopes for his time, so his observations were isolated, and as they would say now – non-reproducible. However, this circumstance only seems objective, since nothing prevented the scientists from coming to Delft and personally verify the validity of the Dutch naturalist's reports. Moreover, there was already a precedent in 1676, when the reliability of Leeuwenhoek's information regarding the existence of his "animalcules", to put it mildly, was doubted.

Of course! Imagine a letter that came from an amateur naturalist to the high-brow and prim Royal Society, which contained, for example, the following statement: "There were probably more of them (i.e. animalcules) in my mouth than there were people in the United Kingdom."

The British may have turned their finger at the temple, but, to their credit, they still decided to check the accuracy of the information from Delft by sending a commission headed by Nehemiah Grew, an authoritative microscopist of that time. The pundits looked into Leeuwenhoek's microscope and were convinced of the authenticity of his observations (which, by the way, contributed to the acceptance of Leeuwenhoek into full members of the Society in 1680). But for some reason they did not check the information about the "revival" of dried rotifers, and the commission was not sent [4].

In fact, dear reader has already understood what happened, and this is a normal, natural (and in some ways even necessary) reaction: people are not ready to immediately accept even obvious facts that go against their worldview. The idea that dried "animals" really die, and then come to life again if they are moistened with ordinary (not even holy!) water – did not fit into the minds of Leeuwenhoek's contemporaries. It was not just about dried rotifers "coming to life" in water, but about an encroachment on the dominance of the hypothesis of the spontaneous generation of life in the minds of scientists of the XVIII century!

Although Leeuwenhoek himself said that life does not stop completely and only the appearance of death occurs, but with his observations of "animalcules", which "are not at all a product of decay, as some think", he still shook the age-old confidence in the self-generation of life.

Lazarus of Pavia

The next episode of our excursion dates back to the end of the XVIII century, when Professor Lazzaro Spallanzani of the University of Pavia, having staged a series of witty and technically flawless experiments, said: "I have always seen that the death of rotifers is followed by their resurrection."

The experiment consisted in repeated killing by drying and subsequent revival with water of the same sample with rotifers. The Italian priest saw with his own eyes how the "animals" of Leeuwenhoek were resurrected eleven times (!), after which he admitted that drying deprives the body of life, and moisturizing revives it (Fig. 2).

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Figure 2. It is difficult to tell, looking at the statue of Lazzaro Spallanzani, through whose eyes he studies the frog: the abbot or the professor. One thing is for sure: in contrast to the resurrected biblical Lazarus from Bethany, the "Pavian Lazarus" himself resurrected... however, only rotifers and slow walkers. Drawing from Wikipedia.

But the second half of the Enlightenment was a period of open and uncompromising struggle between supporters of two views on the essence of "life": vitalists and mechanists. The former identified life with a special force that animates and sets in motion inert matter, while the latter considered it the result of a specific organization of inanimate matter. And so, during the described period, vitalists and mechanists grappled for life and death (fortunately – only their concepts) on the issue of reviving dried organisms.

The fundamental nature of the "apple of discord" fully corresponded to the spirit of the Enlightenment. The vitalists could not agree with the mechanicists who claimed that the revival of dried rotifers occurs due to their simple wetting. Water is water, but somewhere there had to be a "life force"... In 1860, the convinced vitalist Felix Pouchet met before the commission of the Paris Biological Society (chaired by the famous physician Paul Brock) in an intellectual duel with L. Dwyer (Fig. 3). The verdict of the commission in favor of the mechanicists was dry and unambiguous: "To recognize the question of reviving rotifers <...> finally resolved."

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Figure 3. Professor of the Medical school of Rouen Felix Pouchet, despite the defeat in the dispute with the mechanists, was faithful to vitalism until his death. This talented French doctor and naturalist managed to serve science and its popularization with glory. So, being the director of the Natural history museum, he made this institution public. For its time, it was an exceptional event in the cultural life of Europe. Drawing from Wikipedia.

The victory of the mechanists was marked by the introduction into scientific usage of the term "suspended animation" (which literally translates as "return to life") "for lifeless beings, but capable of life." This was done by the German physiologist William Preyer, who stated his position in the pamphlet "On the Study of Life" (1873) with a sentence as short as a shot: "Before suspended animation, life is potential, after it – actual."

Thus, biological death is distinguished from suspended animation by its absolutely irreversible nature.

Braking of the "biochemical machine"

According to modern concepts, life is the result of the spatio–temporal organization of a set of very complex biochemical reactions. An integral feature of a living organism is the metabolism with the environment or, in scientific terms, metabolism.

Metabolism, naturally, proceeds at a certain rate, which can fall to the complete disappearance of metabolism (Fig. 4). And that's what is important for understanding the phenomenon of suspended animation: stopping metabolism can occur while preserving the specific structure of living matter. In other words, a living organism is a complex "biochemical machine" that does not have to be broken to stop.

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Figure 4. English entomologist and parasitologist David Keilin in 1952 proposed to distinguish between organisms with normal, slow and absent metabolism. Drawing from Wikipedia.

The effects of a completely different nature can slow down the metabolism. Heat or cold, dehydration or drug poisoning – all this can reduce the intensity of metabolism of both the body as a whole and individual tissues and organs. This phenomenon is of great interest for biomedicine, of course. Therefore, the search for effective "brakes" for the "biochemical machine" is being conducted experimentally.

For example, a group of scientists from the Cancer Research Center named after Hutchinson (USA) decided to give laboratory mice some air with a slight admixture of hydrogen sulfide (the volume concentration of H 2 S was 0.008%). Rodents, inhaling this poisonous stench, were numb for six hours. Their breathing became very rare and shallow, and their body temperature dropped to 15 °With [5].

It seems that the scientists themselves were surprised that the animals did not die. And here are their colleagues from the Center for Research on Resuscitation Methods. Safara (USA) conducted experiments already on larger objects – dogs. They decided to slow down the metabolism in a more radical way than inhaling rotten air: all the blood was released to the animals, replacing it with a strongly cooled saline solution. Dogs, of course, died: their heart did not beat, they did not breathe and gradually cooled down to 7 ° C. After three hours, the saline solution was replaced with blood, standard resuscitation measures were carried out and voila... dogs revived after a "stretched" clinical death [6].

Is it really the suspended animation of mammals?

No, and here's why. The metabolism of mice and dogs in the experiments described above was extremely slowed down, but not stopped (as required by the definition of the status of "suspended animation"). The state of severely inhibited metabolism is called "hypobiosis", and it is quite widely represented in the wild as one of the ways to survive in extreme conditions.

Hypobiosis is already found in the oldest single–celled forms of life - bacteria, the evolution of which fostered the so-called "resting forms" and "cysts", as states of slow metabolism resistant to extreme environmental conditions [7, 8]. In the plant kingdom, with its sluggish vegetative life, the hypobiotic state of autumn-spring rest of various organs (for example, roots and tubers) is a fairly common phenomenon [9]. The evolution of animals also could not ignore hypobiosis as an option to "live to better times". Insects, amphibians and reptiles are able to stay in this state when the so-called diapause occurs, including winter rigor mortis (Fig. 5).

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Figure 5. Winter rigor mortis of the forest frog (Rana sylvatica) is a vivid example of hypobiosis in vertebrates. Almost half of the water in her body freezes, and the frog turns into a piece of ice. However, one nuance leaves her a chance to thaw safely in the spring: only the water that is under the skin and between muscle cells freezes, whereas in vital organs, it remains liquid [10, 11]. Figure from [2].

The Sleeping Beauty Problem

A normal night's sleep is associated with a decrease in the intensity of metabolism, when vital processes are suppressed, and the body recovers its strength in relative safety for the next day. Sleep as a way of experiencing unfavorable conditions has received its evolutionary and logical conclusion in the form of hibernation (or simply hibernation). This state of slow metabolism allows you to save energy during periods of heat, frost and /or starvation, accompanied by respiratory depression and a decrease in body temperature. The latter circumstance, as it turned out, is deadly for all warm-blooded. Why is that?

It turned out that a study of more than four thousand (!) species of lower fungi revealed that the temperature for optimal growth of their colonies should not exceed 30 ° C. More than 70% of them die at 37 °C, and only 5% survive at 41 °C.

It turns out that the normal body temperature of most warm-blooded animals prevents the development of fungal microflora, and its noticeable decrease, on the contrary, makes the body vulnerable to fungi. And this is confirmed by zoologists on the example of an ancient mammal prone to fungal diseases – the platypus, whose body temperature due to a slow metabolism is only 32 ° C. And in hibernating bats, the body temperature drops so much that they become victims of the "white nose disease", the causative agent of which – the fungus Geomyces destructans – refuses to reproduce at temperatures above 20 ° C. The animal that has fallen asleep for the winter is covered with a dense white fungal coating, which in 95% of cases does not allow it to wake up ever again [12].

So, if the fairy tale about the sleeping beauty had become a reality, then the prince could well have run into a body completely covered with fungi. Would he dare to wake her up with a kiss after that?.. Unlikely. Therefore, what has been said about fungi should be taken into account when developing and improving methods of immersing a person in hypobiosis.

In natural conditions, it is not typical for our species to "run away to sleep" from the problems that have arisen. All we need is a relatively short sleep to recuperate after the tedious conquest of the hostile forces of nature. However, artificially, for purely medical purposes, the human body can be put into a real hibernation – the so-called "artificial coma". This is done only in intensive care units and intensive care units by injecting anesthetics into the patient's blood.

In a state of artificial coma, the pulse becomes rare, and breathing is so depressed that the patient has to be connected to a ventilator. At the same time, the body temperature drops to 33 ° C, which makes it vulnerable to fungal diseases. And this is only one, and not the biggest, problem. After an artificial coma, a minimum annual recovery and rehabilitation period is required, which is why it is considered an extreme measure of human health impact. Also in clinical practice, it is believed that recovery is impossible after a six-month stay in a coma.

Against the background of what has been said, it is surprising, but a fact: this unnatural for a person "plant" form of existence itself has a therapeutic effect. Thus, a series of clinical studies have proven the effectiveness of artificial coma for the treatment of severe forms of increased intracranial pressure [13]. There are reports of cases of even rabies being cured by an artificial coma [14].

Life at a minimum

Slowing down of metabolism is a consequence of dehydration of both individual tissues and organs, and the body as a whole. Bacterial spores, plant seeds, insect pupae, and bird eggs are all diverse and partially dehydrated life forms. The small amount of water that they contain only allows life processes to smolder, justifying the poetic phrase once expressed - vita minima.

Hypobiosis is a slowdown in the course of ontogenesis as a whole. Therefore, it is interesting, first of all, as a method of slowing down one of the stages of ontogenesis – aging. However, the picture of an artificial coma immediately appears before the inner eye. It is unlikely that the extended life of a vegetable person is better than usual... Another thing: the breakdown of ontogenesis into a sequence of episodes of full life and "reversible death" – suspended animation. So far, this is the only theoretically possible way to artificially "stretch" life expectancy and slow down aging.

Literature

  1. Schmidt P.Y. Anabioz. M.: USSR Academy of Sciences, 1948. – 381 p.;

  2. biomolecule: "From the living to the inanimate and back";

  3. Keilin D. (1959). The Leeuwenhoek lecture. The problem of anabiosis or latent life: history and current concept. Proc. R. Soc. B. 150, 149–191;

  4. Anthony van Leeuwenhoek. Website "Biology. Electronic encyclopedia";

  5. Elements: "Suspended animation will prolong your life";

  6. Elements: "Dogs have learned to immerse in suspended animation";

  7. Barrer M.R. Physiological and molecular aspects of growth, non-growth, culturability and viability in bacteria. In: Dormancy and low-growth state in microbial disease / ed. by A.R.M. Coats. Cambridge University Press, 2003. P. 1–37;

  8. Gray J.V., Petsko G.A., Johnston G.C., Ringe D., Singer R.A., Werner-Washburne M. (2004). «Sleeping Beauty»: quiescence in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Revs. 68, 187–206;

  9. Goldovsky A.M. Anabiosis / Ed. by E.M. Kreps. L.: Nauka, 1981. – 136 p.;

  10. Storey K.B. and Storey J.M. (1984). Biochemical adaption for freezing tolerance in the wood frog, Rana sylvatica. J. Comp. Physiol. B. 155, 29–36;

  11. Costanzo J.P., Lee R.E. Jr, Lortz P.H. (1993). Glucose concentration regulates freeze tolerance in the wood frog Rana sylvatica. J. Exp. Biol. 181, 245–255;

  12. Frolov Yu. (2013). Why 36.6? Science and Life. 4;

  13. Lee M.W., Deppe S.A., Sipperly M.E., Barrette R.R., Thompson D.R. (1994). The efficacy of barbiturate coma in the management of uncontrolled intracranial hypertension following neurosurgical trauma. J. Neurotrauma. 11, 325–331;

  14. Artificial coma – application and symptoms. Medbooking website.

Ending: Death on demand

Portal "Eternal youth" http://vechnayamolodost.ru 24.02.2015

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