The Nobel Prize in Medicine was awarded for cancer immunotherapy. Nobel Prize in Physiology or Medicine. Dossier Who received the Nobel Prize in Biology

In 2018, the Nobel Prize in Physiology or Medicine was won by two scientists from different parts of the world - James Ellison from the USA and Tasuku Honjo from Japan - who independently discovered and studied the same phenomenon. They discovered two different checkpoints - mechanisms by which the body suppresses the activity of T-lymphocytes, killer immune cells. If these mechanisms are blocked, T-lymphocytes are “freed” and sent to battle cancer cells. This is called cancer immunotherapy, and it has been used in clinics for several years.

The Nobel Committee loves immunologists: at least one in ten prizes in physiology or medicine are awarded for theoretical immunological work. In the same year, we started talking about practical achievements. The 2018 Nobel laureates were noted not so much for their theoretical discoveries, but for the consequences of these discoveries, which have been helping cancer patients in the fight against tumors for six years now.

The general principle of interaction of the immune system with tumors is as follows. As a result of mutations, tumor cells produce proteins that differ from the “normal” proteins to which the body is accustomed. Therefore, T cells react to them as if they were foreign objects. In this they are helped by dendritic cells - spy cells that crawl through the tissues of the body (for their discovery, by the way, they were awarded the Nobel Prize in 2011). They absorb all the proteins floating by, break them down and display the resulting pieces on their surface as part of the MHC II protein complex (major histocompatibility complex, for more details, see: Mares determine whether to become pregnant or not, according to the major histocompatibility complex... of their neighbor, “Elements” , 01/15/2018). With such baggage, dendritic cells are sent to the nearest lymph node, where they show (present) these pieces of captured proteins to T lymphocytes. If the killer T-cell (cytotoxic lymphocyte, or killer lymphocyte) recognizes these antigen proteins with its receptor, then it is activated and begins to multiply, forming clones. Then the clone cells scatter throughout the body in search of target cells. On the surface of every cell in the body there are MHC I protein complexes in which pieces of intracellular proteins hang. The killer T cell searches for an MHC I molecule with a target antigen that it can recognize with its receptor. And as soon as recognition has occurred, the killer T cell kills the target cell by making holes in its membrane and launching apoptosis (a death program) in it.

But this mechanism does not always work effectively. A tumor is a heterogeneous system of cells that use a variety of ways to evade the immune system (read about one of the recently discovered methods in the news Cancer cells increase their diversity by merging with immune cells, “Elements”, 09.14.2018). Some tumor cells hide MHC proteins from their surface, others destroy defective proteins, and others secrete substances that suppress the immune system. And the “angrier” the tumor, the less chance the immune system has to cope with it.

Classic methods of fighting a tumor involve different ways of killing its cells. But how to distinguish tumor cells from healthy ones? Typically, the criteria used are “active division” (cancer cells divide much more intensively than most healthy cells in the body, and this is targeted by radiation therapy, which damages DNA and prevents division) or “resistance to apoptosis” (chemotherapy helps fight this). With this treatment, many healthy cells, such as stem cells, are affected, and inactive cancer cells, such as dormant cells, are not affected (see: , “Elements”, 06/10/2016). Therefore, now they often rely on immunotherapy, that is, the activation of the patient’s own immunity, since the immune system distinguishes a tumor cell from a healthy one better than external drugs. You can activate your immune system in a variety of ways. For example, you can take a piece of a tumor, develop antibodies to its proteins and introduce them into the body so that the immune system can “see” the tumor better. Or take immune cells and “train” them to recognize specific proteins. But this year the Nobel Prize is being awarded for a completely different mechanism - for removing the blockage from killer T cells.

When this story first began, no one was thinking about immunotherapy. Scientists have tried to unravel the principle of interaction between T cells and dendritic cells. Upon closer examination, it turns out that not only MHC II with the antigen protein and the T-cell receptor are involved in their “communication”. Next to them on the surface of cells there are other molecules that also participate in the interaction. This entire structure - many proteins on membranes that connect to each other when two cells meet - is called an immune synapse (see Immunological synapse). This synapse includes, for example, costimulatory molecules (see Co-stimulation) - the same ones that send a signal to T-killers to activate and go in search of the enemy. They were discovered first: the CD28 receptor on the surface of the T cell and its ligand B7 (CD80) on the surface of the dendritic cell (Fig. 4).

James Ellison and Tasuku Honjo independently discovered two more possible components of the immune synapse - two inhibitory molecules. Ellison worked on the CTLA-4 molecule discovered in 1987 (cytotoxic T-lymphocyte antigen-4, see: J.-F. Brunet et al., 1987. A new member of the immunoglobulin superfamily - CTLA-4). It was initially thought to be another costimulator because it only appeared on activated T cells. Ellison's merit is that he suggested that the opposite is true: CTLA-4 appears on activated cells specifically so that they can be stopped! (M. F. Krummel, J. P. Allison, 1995. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation). It later turned out that CTLA-4 is similar in structure to CD28 and can also bind to B7 on the surface of dendritic cells, and even stronger than CD28. That is, on every activated T cell there is an inhibitory molecule that competes with the activating molecule to receive the signal. And since the immune synapse includes many molecules, the result is determined by the ratio of signals - how many CD28 and CTLA-4 molecules were able to contact B7. Depending on this, the T-cell either continues to work or freezes and cannot attack anyone.

Tasuku Honjo discovered another molecule on the surface of T cells - PD-1 (its name is short for programmed death), which binds to the ligand PD-L1 on the surface of dendritic cells (Y. Ishida et al., 1992. Induced expression of PD- 1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death). It turned out that mice knockout for the PD-1 gene (deprived of the corresponding protein) develop something similar to systemic lupus erythematosus. It is an autoimmune disease, which is a condition where immune cells attack the body's normal molecules. Therefore, Honjo concluded that PD-1 also acts as a blocker, restraining autoimmune aggression (Fig. 5). This is another manifestation of an important biological principle: every time a physiological process starts, the opposite one (for example, the coagulation and anticoagulation systems of the blood) is started in parallel in order to avoid “overfulfillment of the plan,” which can be detrimental to the body.

Both blocking molecules - CTLA-4 and PD-1 - and their corresponding signaling pathways were called immune checkpoints. checkpoint- checkpoint, see Immune checkpoint). Apparently, this is an analogy with cell cycle checkpoints (see Cell cycle checkpoint) - moments at which the cell “makes a decision” whether it can continue dividing further or whether some of its components are significantly damaged.

But the story didn't end there. Both scientists decided to find a use for the newly discovered molecules. Their idea was that they could activate immune cells if they blocked the blockers. True, autoimmune reactions will inevitably be a side effect (as is now happening in patients treated with checkpoint inhibitors), but this will help defeat the tumor. Scientists proposed blocking blockers using antibodies: by binding to CTLA-4 and PD-1, they mechanically close them and prevent them from interacting with B7 and PD-L1, while the T cell does not receive inhibitory signals (Fig. 6).

At least 15 years passed between the discovery of checkpoints and the approval of drugs based on their inhibitors. Currently, six such drugs are used: one CTLA-4 blocker and five PD-1 blockers. Why were PD-1 blockers more successful? The fact is that many tumor cells also carry PD-L1 on their surface to block the activity of T cells. Thus, CTLA-4 activates killer T cells in general, while PD-L1 acts more specifically on tumors. And there are slightly fewer complications with PD-1 blockers.

Modern methods of immunotherapy, unfortunately, are not yet a panacea. Firstly, checkpoint inhibitors still do not provide 100% patient survival. Secondly, they do not act on all tumors. Thirdly, their effectiveness depends on the patient’s genotype: the more diverse his MHC molecules, the higher the chance of success (on the diversity of MHC proteins, see: Diversity of histocompatibility proteins increases reproductive success in male warblers and reduces it in females, “Elements”, 29.08 .2018). Nevertheless, it turned out to be a beautiful story about how a theoretical discovery first changes our understanding of the interaction of immune cells, and then gives birth to drugs that can be used in the clinic.

And Nobel laureates have something to work on further. The exact mechanisms of how checkpoint inhibitors work are still not fully known. For example, in the case of CTLA-4, it is still unclear which cells the blocking drug interacts with: with the T-killer cells themselves, or with dendritic cells, or even with T-regulatory cells - the population of T-lymphocytes responsible for suppressing the immune response . Therefore, this story is, in fact, still far from over.

Polina Loseva

The history of the Nobel Prize is very long. I'll try to tell it briefly.

Alfred Nobel left a will, with which he officially confirmed his desire to invest all his savings (about 33,233,792 Swedish kronor) in the development and support of science. In fact, this was the main catalyst of the 20th century, which contributed to the advancement of modern scientific hypotheses.

Alfred Nobel had a plan, an incredible plan, which became known only after his will was opened in January 1897. The first part contained the usual instructions for such a case. But after these paragraphs there were others that said:

“All my movable and immovable property must be converted by my executors into liquid assets, and the capital thus collected must be placed in a reliable bank. These funds will belong to a fund, which will annually hand over the income from them in the form of a bonus to those who during the past year has made the most significant contribution to science, literature or peace and whose activities have brought the greatest benefit to mankind. Prizes for achievements in chemistry and physics shall be awarded by the Swedish Academy of Sciences, Prize for Achievement in Physiology and Medicine - Karolinska Institutet, the Literature Prize by the Stockholm Academy, the Peace Prize by a five-member commission appointed by the Storting of Norway. It is also my final wish that the prizes should be awarded to the most deserving candidates, whether they are Scandinavian or not. Paris, November 27, 1895"

Institute administrators are elected by some organizations. Each member of the administration is kept confidential until the discussion. He can belong to any nationality. There are fifteen Nobel Prize administrators in total, three for each prize. They appoint the administrative council. The President and Vice-President of this council are appointed by the King of Sweden respectively.

Anyone who proposes their candidacy will be disqualified. A candidate in his or her field may be nominated by a previous winner of the award, the organization responsible for presenting the award, or the person who nominates the award impartially. Presidents of academies, literary and scientific societies, some international parliamentary organizations, scientists working at large universities, and even members of governments also have the right to nominate their candidate. Here, however, it is necessary to clarify: only famous people and large organizations can nominate their candidate. It is important that the candidate has nothing to do with them.

These organizations, which may seem too rigid, are excellent evidence of Nobel's distrust of human weaknesses.

Nobel's fortune, which included property worth more than thirty million crowns, was divided into two parts. The first - 28 million crowns - became the main fund of the award. With the remaining money, the building in which it is still located was purchased for the Nobel Foundation, in addition, funds were allocated from this money to the organizational funds of each prize and amounts for expenses for organizations that are part of the Nobel Foundation.

whom the committee.

Since 1958, the Nobel Foundation has invested in bonds, real estate and stocks. There are certain restrictions on investing abroad. These reforms were driven by the need to protect capital from inflation. It is clear that in our time this means a lot.

Let's look at some interesting examples of award presentations throughout its history.

Alexander FLEMING.

Alexander Fleming was awarded the prize for the discovery of penicillin and its healing effects in various infectious diseases. The happy accident - Fleming's discovery of penicillin - was the result of a combination of circumstances so incredible that they are almost impossible to believe, and the press received a sensational story that could capture the imagination of any person. In my opinion, he made an invaluable contribution (yes, I think everyone will agree with me that scientists like Fleming will never be forgotten, and their discoveries will always invisibly protect us). We all know that the role of penicillin in medicine is difficult to overestimate. This drug saved the lives of many people (including in the war, where thousands of people died from infectious diseases).

Howard W. FLORY. Nobel Prize in Physiology or Medicine, 1945

Howard Florey received the prize for the discovery of penicillin and its healing effects on various infectious diseases. Penicillin, discovered by Fleming, was chemically unstable and could be obtained only in small quantities. Flory led the research into the drug. He established the production of penicillin in the USA, thanks to the huge allocations allocated for the project.

Ilya MECHNIKOV. Nobel Prize in Physiology or Medicine, 1908

Russian scientist Ilya Mechnikov was awarded a prize for his work on immunity. Mechnikov's most important contribution to science was of a methodological nature: the scientist's goal was to study “immunity in infectious diseases from the standpoint of cellular physiology.” Mechnikov's name is associated with a popular commercial method of making kefir. Of course, M.’s discovery was great and very useful; with his works he laid the foundations for many subsequent discoveries.

Ivan PAVLOV. Nobel Prize in Physiology or Medicine, 1904

Ivan Pavlov was awarded a prize for his work on the physiology of digestion. Experiments concerning the digestive system led to the discovery of conditioned reflexes. Pavlov's skill in surgery was unsurpassed. He was so good with both hands that you never knew which hand he would use next.

Camillo GOLGI. Nobel Prize in Physiology or Medicine, 1906

In recognition of his work on the structure of the nervous system, Camillo Golgi was awarded the prize. Golgi classified the types of neurons and made many discoveries about the structure of individual cells and the nervous system as a whole. The Golgi apparatus, a fine network of interwoven filaments within nerve cells, is recognized and thought to be involved in protein modification and secretion. This unique scientist is known to everyone who has studied the structure of cells. Including me and our entire class.

Georg BEKESHI. Nobel Prize in Physiology or Medicine, 1961

Physicist Georg Bekesi studied the membranes of telephone sets, which distorted sound vibrations, unlike the eardrum. In this regard, he began to study the physical properties of the hearing organs. Having recreated a complete picture of the biomechanics of the cochlea, modern otosurgeons have the opportunity to implant artificial eardrums and auditory ossicles. This work by Bekeshi was awarded a prize. These discoveries become especially relevant in our time, when computer technology has developed to incredible proportions and the problem of implantation is moving to a qualitatively different level. With his discoveries, he made it possible for many people to hear again.

Emil von BERING. Nobel Prize in Physiology or Medicine, 1901

For his work on serum therapy, mainly for its use in the treatment of diphtheria, which opened new paths in medical science and put into the hands of doctors a victorious weapon against disease and death, Emil von Behring was awarded the prize. During the First World War, the tetanus vaccine created by Bering saved the lives of many German soldiers. Of course, these were just the basics of medicine. But no one probably doubts that this discovery gave a lot for the development of medicine and for all humanity in general. His name will forever remain etched in the history of mankind.

George W. BEADLE. Nobel Prize in Physiology or Medicine, 1958

George Beadle received the prize for his discoveries concerning the role of genes in specific biochemical processes. Experiments have proven that certain genes are responsible for the synthesis of specific cellular substances. Laboratory methods developed by George Beadle and Edward Tatham proved useful in increasing the pharmacological production of penicillin, an important substance produced by special fungi. Everyone probably knows about the existence of the above-mentioned penicillin and its significance, therefore the role of the discovery of these scientists is invaluable in modern society.

The Nobel Committee today announced the winners of the 2017 Prize in Physiology or Medicine. This year the prize will travel to the United States again, with Michael Young of The Rockefeller University in New York, Michael Rosbash of Brandeis University and Jeffrey Hall of the University of Maine sharing the award. According to the decision of the Nobel Committee, these researchers were awarded “for their discoveries of the molecular mechanisms that control circadian rhythms.”

It must be said that in the entire 117-year history of the Nobel Prize, this is perhaps the first prize for studying the sleep-wake cycle, or for anything related to sleep in general. The famous somnologist Nathaniel Kleitman did not receive the award, and Eugene Azerinsky, who made the most outstanding discovery in this field, who discovered REM sleep (REM - rapid eye movement, rapid eye movement phase), generally received only a PhD degree for his achievement. It is not surprising that in numerous forecasts (we talk about them in our article) any names and any research topics were mentioned, but not those that attracted the attention of the Nobel Committee.

Why was the award given?

So, what are circadian rhythms and what exactly did the laureates discover, who, according to the secretary of the Nobel Committee, greeted the news of the award with the words “Are you kidding me?”

Jeffrey Hall, Michael Rosbash, Michael Young

Circa diem translated from Latin as “around the day.” It just so happens that we live on planet Earth, where day gives way to night. And in the course of adaptation to different conditions of day and night, organisms developed internal biological clocks - rhythms of the biochemical and physiological activity of the body. It was possible to show that these rhythms have an exclusively internal nature only in the 1980s, by sending mushrooms into orbit Neurospora crassa. Then it became clear that circadian rhythms do not depend on external light or other geophysical signals.

The genetic mechanism of circadian rhythms was discovered in the 1960s and 1970s by Seymour Benzer and Ronald Konopka, who studied mutant lines of Drosophila with different circadian rhythms: in wild-type flies the circadian rhythm oscillations had a period of 24 hours, in some mutants - 19 hours, in others - 29 hours, and for others there was no rhythm at all. It turned out that the rhythms are regulated by the gene PER - period. The next step, which helped to understand how such fluctuations in the circadian rhythm appear and are maintained, was taken by the current laureates.

Self-regulating clock mechanism

Geoffrey Hall and Michael Rosbash proposed that the gene encoded period The PER protein blocks the operation of its own gene, and this feedback loop allows the protein to prevent its own synthesis and cyclically, continuously regulate its level in cells.

The picture shows the sequence of events over a 24 hour oscillation. When the gene is active, the PER mRNA is produced. It exits the nucleus into the cytoplasm, becoming a template for the production of the PER protein. The PER protein accumulates in the cell nucleus when the activity of the period gene is blocked. This closes the feedback loop.

The model was very attractive, but a few pieces of the puzzle were missing to complete the picture. To block gene activity, the protein needs to get into the cell nucleus, where the genetic material is stored. Jeffrey Hall and Michael Rosbash showed that the PER protein accumulates in the nucleus overnight, but they did not understand how it managed to get there. In 1994, Michael Young discovered a second circadian rhythm gene, timeless(English: “timeless”). It encodes the TIM protein, which is needed for the normal functioning of our internal clock. In his elegant experiment, Young demonstrated that only by binding to each other can TIM and PER pair up to enter the cell nucleus, where they block the gene period.

Simplified illustration of the molecular components of circadian rhythms

This feedback mechanism explained the reason for the oscillations, but it was not clear what controlled their frequency. Michael Young found another gene doubletime. It contains the DBT protein, which can delay the accumulation of the PER protein. This is how the oscillations are “debugged” so that they coincide with the daily cycle. These discoveries revolutionized our understanding of the key mechanisms of the human biological clock. Over the following years, other proteins were found that influence this mechanism and maintain its stable operation.

For example, this year's laureates discovered additional proteins that cause the gene period work, and proteins with the help of which light synchronizes the biological clock (or, with a sharp change in time zones, causes jet lag).

About the award

Let us recall that the Nobel Prize in Physiology or Medicine (it is worth noting that in the original title the preposition “or” sounds in place of “and”) is one of the five prizes defined by Alfred Nobel’s will in 1895 and, if we follow the letter of the document, should be awarded annually “for a discovery or invention in the field of physiology or medicine” made in the previous year and bringing maximum benefit to humanity. However, it seems that the “principle of last year” was almost never followed.

Now the Prize in Physiology or Medicine is traditionally awarded at the very beginning of the Nobel week, on the first Monday in October. It was first awarded in 1901 for the creation of serum therapy for diphtheria. In total, throughout history, the prize was awarded 108 times, in nine cases: in 1915, 1916, 1917, 1918, 1921, 1925, 1940, 1941 and 1942 - the prize was not awarded.

From 1901 to 2017, the prize was awarded to 214 scientists, a dozen of whom were women. So far there has not been a case where someone received the prize in medicine twice, although there have been cases when an existing laureate was nominated (for example, ours). If you do not take into account the 2017 award, the average age of the laureate was 58 years. The youngest Nobel laureate in the field of physiology and medicine was the 1923 laureate Frederick Banting (award for the discovery of insulin, age 32 years), the oldest was the 1966 laureate Peyton Rose (award for the discovery of oncogenic viruses, age 87 years).

As reported on the website of the Nobel Committee, having studied the behavior of fruit flies in various phases of the day, researchers from the United States were able to look inside the biological clocks of living organisms and explain the mechanism of their work.

Geneticist Jeffrey Hall, 72, of the University of Maine, his colleague Michael Rosbash, 73, of the private Brandeis University, and Michael Young, 69, of Rockefeller University, have discovered how plants, animals and people adapt to the cycle of day and night. Scientists have discovered that circadian rhythms (from the Latin circa - “about”, “around” and the Latin dies - “day”) are regulated by so-called period genes, which encode a protein that accumulates in the cells of living organisms at night and is consumed during the day.

2017 Nobel laureates Jeffrey Hall, Michael Rosbash and Michael Young began exploring the molecular biological nature of the internal clocks of living organisms in 1984.

“The biological clock regulates behavior, hormone levels, sleep, body temperature and metabolism. Our well-being worsens if there is a discrepancy between the external environment and our internal biological clock - for example, when we travel across multiple time zones. The Nobel laureates found signs that a chronic mismatch between a person's lifestyle and their biological rhythm, dictated by the internal clock, increases the risk of various diseases,” the Nobel Committee says on its website.

Top 10 Nobel laureates in the field of physiology and medicine

There, on the website of the Nobel Committee, there is a list of the ten most popular laureates of the prize in the field of physiology and medicine for the entire time that it has been awarded, that is, since 1901. This ranking of Nobel Prize winners was compiled by the number of views of website pages dedicated to their discoveries.

On the tenth line- Francis Crick, British molecular biologist who received the Nobel Prize in 1962, together with James Watson and Maurice Wilkins, “for their discoveries concerning the molecular structure of nucleic acids and their importance for the transmission of information in living systems,” or in other words, for their study of DNA.

On the eighth line Among the most popular Nobel laureates in the field of physiology and medicine is immunologist Karl Landsteiner, who received the prize in 1930 for his discovery of human blood groups, which made blood transfusions a common medical practice.

In seventh place- Chinese pharmacologist Tu Youyou. Together with William Campbell and Satoshi Omura, she received the Nobel Prize in 2015 “for discoveries in the field of new treatments for malaria,” or rather, for the discovery of artemisinin, a drug from Artemisia annua that helps fight this infectious disease. Note that Tu Youyou became the first Chinese woman to be awarded the Nobel Prize in Physiology or Medicine.

In fifth place Among the most popular Nobel laureates is the Japanese Yoshinori Ohsumi, winner of the 2016 Prize in Physiology or Medicine. He discovered the mechanisms of autophagy.

On the fourth line- Robert Koch, German microbiologist who discovered the anthrax bacillus, Vibrio cholerae and tuberculosis bacillus. Koch received the Nobel Prize in 1905 for his research on tuberculosis.

On the third place The ranking of Nobel Prize laureates in the field of physiology or medicine is the American biologist James Dewey Watson, who received the award along with Francis Crick and Maurice Wilkins in 1952 for the discovery of the structure of DNA.

Well and most popular Nobel laureate in the field of physiology and medicine was Sir Alexander Fleming, a British bacteriologist who, together with colleagues Howard Florey and Ernest Boris Chain, received the prize in 1945 for the discovery of penicillin, which truly changed the course of history.

In 2017, the Nobel Prize in Medicine was awarded to three American scientists who discovered the molecular mechanisms responsible for the circadian rhythm - the human biological clock. These mechanisms regulate sleep and wakefulness, the functioning of the hormonal system, body temperature and other parameters of the human body, which change depending on the time of day. Read more about the discovery of scientists in the RT material.

Winners of the Nobel Prize in Physiology or Medicine Reuters Jonas Ekstromer

The Nobel Committee of the Karolinska Institute in Stockholm on Monday, October 2, announced that the 2017 Nobel Prize in Physiology or Medicine was awarded to American scientists Michael Young, Geoffrey Hall and Michael Rosbash for their discoveries of the molecular mechanisms that control the circadian rhythm.

“They were able to get inside the body’s biological clock and explain how it works,” the committee noted.

Circadian rhythms are called cyclic fluctuations of various physiological and biochemical processes in the body associated with the change of day and night. Almost every organ of the human body contains cells that have an individual molecular clock mechanism, and therefore circadian rhythms represent a biological chronometer.

According to a release from the Karolinska Institutet, Young, Hall and Rosbash were able to isolate a gene in fruit flies that controls the release of a special protein depending on the time of day.

“Thus, scientists were able to identify the protein compounds that are involved in the operation of this mechanism and understand the independent mechanics of this phenomenon inside each individual cell. We now know that the biological clock works on the same principle in the cells of other multicellular organisms, including humans,” the committee that awarded the prize said in a release.

Drosophila fly
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imagebroker/Alfred Schauhuber

The presence of biological clocks in living organisms was established at the end of the last century. They are located in the so-called suprachiasmatic nucleus of the hypothalamus of the brain. The nucleus receives information about light levels from receptors on the retina and sends signals to other organs through nerve impulses and hormonal changes.

In addition, some nuclear cells, like the cells of other organs, have their own biological clock, the work of which is ensured by proteins whose activity changes depending on the time of day. The activity of these proteins determines the synthesis of other protein bonds, which generate circadian rhythms in the life of individual cells and entire organs. For example, being indoors with bright lighting at night can shift the circadian rhythm, activating protein synthesis of PER genes that usually begins in the morning.

The liver also plays a significant role in circadian rhythms in mammals. For example, rodents like mice or rats are nocturnal animals and eat in the dark. But if food becomes available only during the day, their liver circadian cycle shifts by 12 hours.

Rhythm of life

Circadian rhythms are daily changes in the body's activity. They include the regulation of sleep and wakefulness, the release of hormones, body temperature and other parameters that change in accordance with the circadian rhythm, explains somnologist Alexander Melnikov. He noted that researchers have been developing in this direction for several decades.

“First of all, it should be noted that this discovery is not yesterday or today. These studies were carried out for many decades - from the 80s of the last century to the present - and made it possible to discover one of the deep mechanisms that regulate the nature of the human body and other living beings. The mechanism that scientists discovered is very important for influencing the body’s circadian rhythm,” said Melnikov.

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According to the expert, these processes occur not only due to the change of day and night. Even in polar night conditions, circadian rhythms will continue to operate.

“These factors are very important, but very often they are impaired in people. These processes are regulated at the gene level, which was confirmed by the award winners. Nowadays, people very often change time zones and are exposed to various stresses associated with sudden changes in the circadian rhythm. The intense rhythm of modern life can affect the correct regulation and opportunities for rest of the body,” concluded Melnikov. He is confident that the research of Young, Hall and Rosbash provides an opportunity to develop new mechanisms for influencing the rhythms of the human body.

History of the award

The founder of the prize, Alfred Nobel, in his will entrusted the selection of the laureate in physiology and medicine to the Karolinska Institute in Stockholm, founded in 1810 and one of the leading educational and scientific medical centers in the world. The university's Nobel Committee consists of five permanent members, who, in turn, have the right to invite experts for consultation. There were 361 names on the list of nominees for this year's award.

The Nobel Prize in Medicine has been awarded 107 times to 211 scientists. Its first laureate was in 1901 the German doctor Emil Adolf von Behring, who developed a method of immunization against diphtheria. The Karolinska Institute Committee considers the most significant prize to be the 1945 prize awarded to British scientists Fleming, Cheyne and Florey for the discovery of penicillin. Some awards have become irrelevant over time, such as the award awarded in 1949 for the development of the lobotomy method.

In 2017, the bonus amount was increased from 8 million to 9 million Swedish kronor (about $1.12 million).

The award ceremony will traditionally take place on December 10, the day of the death of Alfred Nobel. Prizes in the fields of physiology and medicine, physics, chemistry and literature will be awarded in Stockholm. The Peace Prize, according to Nobel's will, is awarded on the same day in Oslo.