1 Nobel Prize in Medicine. Nobel Prizes in Medicine and Biology and its laureates
Nobel Prize in Physiology or Medicine. Its owners were a group of scientists from the United States. Michael Young, Jeffrey Hall, and Michael Rosbash received the award for discovering the molecular mechanisms that control the circadian rhythm.
According to the will of Alfred Nobel, the prize is awarded to the one "who makes an important discovery" in this field. The editors of TASS-DOSIER have prepared material on the procedure for awarding this award and its laureates.
Awarding and nominating candidates
The Nobel Assembly of the Karolinska Institute in Stockholm is responsible for awarding the prize. The Assembly consists of 50 professors of the Institute. Its working body is the Nobel Committee. It consists of five people elected by the assembly from among its members for three years. The Assembly meets several times a year to discuss the applicants selected by the committee, and on the first Monday in October elects the laureate by majority vote.
Scholars are eligible to nominate different countries, including members of the Karolinska Institute Nobel Assembly and Nobel Prize winners in Physiology or Medicine and Chemistry, who received special invitations from the Nobel Committee. You can propose candidates from September until January 31 of the following year. 361 people apply for the award in 2017.
Laureates
The prize has been awarded since 1901. The first winner was german doctor, microbiologist and immunologist Emil Adolf von Behring, who developed a method of immunization against diphtheria. In 1902, Ronald Ross (Great Britain), who studied malaria, received the award; in 1905 - Robert Koch (Germany), who studied the causative agents of tuberculosis; in 1923, Frederick Banting (Canada) and John McLeod (Great Britain), who discovered insulin; in 1924 - the founder of electrocardiography Willem Einthoven (Holland); in 2003 Paul Lauterbur (USA) and Peter Mansfield (UK) developed the method of magnetic resonance imaging.
According to the Nobel Committee of the Karolinska Institute, the 1945 prize awarded to Alexander Fleming, Ernest Cheyne and Howard Flory (Great Britain), who discovered penicillin, remains the most famous. Some discoveries have lost their significance over time. Among them is the lobotomy method used in the treatment of mental illness. For its development in 1949, the Portuguese Antonio Egas-Moniz received the prize.
In 2016, the prize was awarded to the Japanese biologist Yoshinori Ohsumi "for the discovery of the mechanism of autophagy" (the process of processing by the cell of unnecessary contents in it).
According to the Nobel website, today there are 211 people on the list of prize winners, including 12 women. Among the laureates are two of our compatriots: the physiologist Ivan Pavlov (1904; for his work in the field of the physiology of digestion) and the biologist and pathologist Ilya Mechnikov (1908; for the study of immunity).
Statistics
In 1901-2016, the Prize in Physiology or Medicine was awarded 107 times (in 1915-1918, 1921, 1925, 1940-1942, the Nobel Assembly of the Karolinska Institute could not choose a laureate). The prize was shared 32 times between two laureates and 36 times between three. The average age of the laureates is 58 years. The youngest is Canadian Frederick Banting, who received the award in 1923 at the age of 32, the oldest is 87-year-old American Francis Peyton Rose (1966).
5.5. Nobel Prize. Nobel Prize winners in medicine and physiology.
The Nobel Prize was established on June 29, 1900 in accordance with the will of the Swedish industrialist and scientist Alfred Nobel. To this day, it remains the most honored science award in the world.
Alfred Bernhard Nobel (Nobel, Alfred V., 1833-1896) - the inventor of dynamite, was an ardent pacifist. “My discoveries,” he wrote, “are more likely to end all wars than your congresses. When the warring parties discover that they can destroy each other in an instant, people will abandon these horrors and avert war.”
Initially, A. Nobel's idea was to provide assistance to poor talented researchers, which he generously provided. The final idea is the Nobel Fund, the interest from which makes it possible to pay annual Nobel Prizes in the amount of 1 million 400 thousand dollars. Alfred Nobel's will states:
“All the realizable property left after me must be distributed as follows: the capital of my executors must be transferred into securities, creating a fund, interest on which will be issued in the form of a bonus to those who during the previous year have brought the greatest benefit to mankind. The indicated percentages should be divided by five equal parts which are intended: the first part to the one who made the most important discovery or invention in the field of physics, the second - to the one who made a major discovery or improvement in the field of chemistry, the third - to the one who achieved outstanding success in the field of physiology or medicine, the fourth - to the creator the most significant literary work that reflects human ideals, the fifth - to one who will make a significant contribution to the rallying of peoples, the destruction of slavery, the reduction in the number of existing armies and the promotion of a peace agreement. The prizes in physics and chemistry are to be awarded by the Royal Swedish Academy of Sciences, in physiology and medicine by the Royal Karolinska Institute in Stockholm, in literature by the Swedish Academy in Stockholm, and the peace prize by a five-member committee elected by the Norwegian Storting. My particular desire is that the nationality of the candidate should not influence the awarding of prizes, so that the most deserving ones will receive the prize, regardless of whether they are Scandinavians or not."
The mechanism for awarding the Nobel Prize has been established since 1900. Even then, the members of the Nobel Committee decided to collect documented proposals from qualified experts from various countries. The Nobel Prize cannot be awarded jointly to more than three persons. Therefore, a very small number of applicants with outstanding merit can hope for an award.
There is a special Nobel Committee for awarding the award in each direction. The Royal Swedish Academy of Sciences has established three committees - for physics, chemistry and economics. The Karolinska Institute gave its name to the committee that awards prizes in physiology and medicine. The Swedish Academy also elects a literature committee. In addition, the Norwegian parliament, the Storting, elects a committee that awards peace prizes.
Nobel committees play a critical role in the selection process for laureates. Nobel committees get the right to individually approve the applicant. Such individuals include past Nobel Prize winners and members of the Royal Swedish Academy of Sciences, the Nobel Assembly of the Karolinska Institute and the Swedish Academy.
Applications close on February 1st. From now until September, members of the Nobel committees and several thousand consultants evaluate the qualifications of candidates for the award.
It takes a lot of work to select winners. For example, out of 1000 who have received the right to nominate candidates in each of the fields of science, from 200 to 250 people exercise this right. Since the proposals often overlap, the number of valid candidates is somewhat smaller. For example, the Swedish Academy selects from a total of 100 to 150 candidates. It is a rare case when a proposed candidate receives an award from the first submission, many applicants are nominated several times.
Subsequently, the Nobel Foundation invites the laureates and their families to Stockholm and Oslo on 10 December. In Stockholm, the honor ceremony takes place in the Concert Hall in the presence of about 1200 people.
Prizes in the fields of physics, chemistry, physiology and medicine, literature and economics are awarded by the King of Sweden. In Oslo, the Nobel Peace Prize ceremony is held at the university, in the assembly hall, in the presence of the King of Norway and members of the royal family.
The following is a list of Nobel Prize winners in Physiology or Medicine and the exact wording of the decisions of the Nobel committees.
1901. Emil Adolf von Behring (Germany) - for his work on serotherapy, and above all for its use in the fight against diphtheria.
1902. Ronald Ross (Great Britain) - for his work on malaria, which showed how it affects the body, which laid the foundation for important research on this disease and methods of combating it.
1903. Nils Ryberg Finsen (Denmark) - for the method of treating diseases, especially lupus, using concentrated light rays.
1904. Ivan Petrovich Pavlov(Russia) - in recognition of his work on the physiology of digestion, which allowed us to change and expand our knowledge in this area.
1905. Robert Koch (Germany) - for research and discoveries in the field of tuberculosis.
1906. Camillo Golgi (Italy) and Santiago Ramon y Cajal (Spain) - for their work on the study of the structure of the nervous system.
1907. Charles Louis Alphonse Laveran (France) - for his work on the study of the role of protozoa as pathogens.
1908. Ilya Ilyich Mechnikov(Russia) and Paul Ehrlich (Germany) - for their work on immunization (the theory of immunity).
1909. Theodor Kocher (Switzerland) - for work on the physiology, pathology and surgery of the thyroid gland.
1910. Albrecht Kossel (Germany) - for his work on proteins, including nucleins, which contributed to the study of cell chemistry.
1911. Alvar Gullstrand (Sweden) - for his work on the diopter of the eye.
1912. Alexis Carrel (France) - in recognition of his work on vascular suture and vascular and organ transplantation.
1913. Charles Richet (France) - for his work on anaphylaxis.
1914. Robert Barani (Austria) - for work on the physiology and pathology of the vestibular apparatus.
1919. Jules Bordet (Belgium) - for discoveries in the field of immunity.
1922. Archibald Vivien Hill (Great Britain) - for the discovery of the phenomenon of latent heat generation in muscles and Otto Meyerhof (Germany) - for the discovery of the laws governing the absorption of oxygen by the muscle and the formation of lactic acid in it.
1923. Frederick Grant Banting (Canada) and Jack James Rickard McLeod (Great Britain) - for the discovery of insulin.
1924. Willem Einthoven (Netherlands) - for the discovery of the method of electrocardiography.
1926. Johannes Fibiger (Denmark) - for the discovery of spiropteral cancer.
1927. Julius Wagner-Jauregg (Austria) - for the discovery of the therapeutic effect of malaria inoculation in the case of progressive paralysis.
1928. Charles Nicole (France) - for work on typhus.
1929. Christian Aikman (Netherlands) - for the discovery of the anti-neuritic vitamin and Frederick Gowland Hopkins (Great Britain) - for the discovery of the growth vitamin.
1930. Karl Landsteiner (Austria) - for the discovery of human blood groups.
1931. Otto Heinrich Warburg (Germany) - for the discovery of the nature and function of the respiratory enzyme.
1932. Charles Scott Sherrington (Great Britain) and Edgar Douglas Adrian (Great Britain) - for the discovery of the functions of neurons.
1933. Thomas Hunt Morgan (USA) - for the discovery of the function of chromosomes as carriers of heredity.
1934. George Hoyt Whipple (USA), George Richards Minot (USA) and William Parry Murphy (USA) - for the discovery of methods for treating anemia by administering liver extracts.
1935. Hans Spemann (Germany) - for the discovery of the "organizational effect" in the process of embryonic development.
1936. Otto Loewy (Austria) and Henry Hollett Dale (Great Britain) - for the discovery of the chemical nature of the nervous reaction.
1937. Albert Szent-György Nagirapolt (USA) - for discoveries related to biological oxidation, primarily for the study of vitamin C and the catalysis of fumaric acid.
1938. Korney Heymans (Belgium) - for the discovery of the role of the sinus and aortic mechanisms in the regulation of respiration.
1939. Gerhard Damagk (Germany) - for the discovery of the therapeutic effect of prontosil in certain infections.
1943. Henrik Dam (Denmark) - for the discovery of vitamin K and Eduard Adelberg Doisy (USA) - for the discovery of the chemical nature of vitamin K.
1944. Joseph Erlanger (USA) and Herbert Spencer Gasser (USA) - for their discoveries concerning the numerous functional differences between individual nerve fibers.
1945. Alexander Fleming (Great Britain), Ernst Boris Chain (Great Britain) and Howard Walter Flory (Great Britain) - for the discovery of penicillin and its therapeutic effect in the treatment of various infectious diseases.
1946. Herman Joseph Muller (USA) - for the discovery of the occurrence of mutations under the influence of X-rays.
1947. Carl Ferdinand Corey (USA) and Gerty Teresa Corey (USA) - for the discovery of the processes of catalytic glycogen metabolism, as well as Bernardo Alberto Usai (Argentina) - for the discovery of the action of the hormone produced by the anterior pituitary gland on sugar metabolism.
1948. Paul Müller (Switzerland) - for the discovery of the action of DDT as a strong poison for most arthropods.
1949. Walter Rudolf Hess (Switzerland) - for the discovery of the functional organization of the diencephalon and its connection with the activity of internal organs, as well as Antonid Egas Moniz (Portugal) - for the discovery of the therapeutic effect of prefrontal leucotomy in certain mental illnesses.
1950. Philip Showalter Hench (USA), Edward Kendall (USA) and Tadeusz Reichstein (Switzerland) - for research on the hormones of the adrenal cortex, their structure and biological action.
1951. Max Theiler (USA) - for discoveries related to yellow fever and the fight against this disease.
1952. Zelman Waksman (USA) - for the discovery of streptomycin, the first antibiotic effective against tuberculosis.
1953. Hans Adolf Krebs (Great Britain) - for the discovery of the tricarboxylic acid cycle and Fritz Albert Lipmann (USA) - for the discovery of coenzyme A and its role in intermediate metabolism.
1954. John Enders (USA), Frederick Chapman Robbins (USA) and Thomas Hackle Weller (USA) - for the discovery of the ability of the polio virus to multiply in cultures of various tissues.
1955. Axel Hugo Theodor Theorell (Sweden) - for the study of the nature and modes of action of oxidative enzymes.
1956. Andre Frederic Cournan (USA), Werner Forssmann (Germany) and Dickinson Richards (USA) - for discoveries related to cardiac catheterization and pathological changes in the circulatory system.
1957. Diniele Bove (Italy) - for the discovery of synthetic substances capable of blocking the action of certain compounds formed in the body, especially those affecting blood vessels and striated muscles.
1958. George Wells Beadle (USA) and Edward Tatham (USA) - for the discovery of the ability of genes to regulate certain chemical processes ("one gene - one enzyme"), as well as Joshua Lederberg (USA) - for discoveries concerning genetic recombination in bacteria and structures of the genetic apparatus.
1959. Severo Ochoa (USA) and Arthur Kornberg (USA) - for the study of the mechanism of biological synthesis of ribonucleic and deoxyribonucleic acids.
1960. Frank Burnet (Australia) and Peter Brian Medawar (Great Britain) - for studies on acquired immunological tolerance.
1961. Gyorgy Bekesy (Hungary, USA) - for the discovery of the physical mechanism of excitation in the cochlea of the inner ear.
1962. Francis Harry Crick (Great Britain), James Dewey Watson (USA) and Maurice Wilkins (Great Britain) - for establishing the molecular structure of nucleic acids and its role in the transmission of information in living matter.
1963. John Carew Eccles (Australia), Alan Lloyd Hodgkin (Great Britain) and Andrew Fielding Huxley (Great Britain) - for research on ionic mechanisms of excitation and inhibition in the peripheral and central parts of nerve cell membranes.
1964. Konrad Emil Bloch (USA) and Feodor Linen (Germany) - for research into the mechanism of regulation of cholesterol and fatty acid metabolism.
1965. Andre Michel Lvov (France), Francois Jacob (France) and Jacques Lucien Monod (France) - for the discovery of the genetic regulation of the synthesis of enzymes and viruses.
1966. Francis Rose (USA) - for the discovery of tumor viruses and Charles Brenton Huggins (USA) - for the development of methods for treating prostate cancer using hormones.
1967. Ragnar Granit (Sweden), Holden Hartline (USA) and George Wald (USA) - for their study of the visual process.
1968. Robert William Holley (USA), Har Gobind Korana (USA) and Marshall Warren Nirenberg (USA) - for deciphering the genetic code and its function in protein synthesis.
1969. Max Delbrück (USA), Alfred Day Hershey (USA) and Salvador Eduard Luria (USA) - for the discovery of the viral reproduction cycle and the development of the genetics of bacteria and viruses.
1970. Ulf von Euler (Sweden), Julius Axelrod (USA) and Bernard Katz (Great Britain) - for the discovery of signal substances in the contact organs of nerve cells and the mechanisms of their accumulation, release and deactivation.
1971. Earl Wilbur Sutherland (USA) - for research on the mechanism of action of hormones.
1972. Gerald Maurice Edelman (USA) and Rodney Robert Porter (Great Britain) - for establishing the chemical structure of antibodies.
1973. Karl von Frisch (Germany), Konrad Lorenz (Austria) and Nicholas Tanbergen (Netherlands, Great Britain) - for the creation and use in practice of models of individual and group behavior.
1974. Albert Claude (Belgium), Christian Rene de Duve (Belgium) and George Emile Palade (USA) - for studies of the structural and functional organization of the cell.
1975. Renato Dulbecco (USA) - for the study of the mechanism of action of oncogenic viruses, as well as Howard Martin Temin (USA) and David Baltimore (USA) - for the discovery of reverse transcriptase.
1976. Baruch Blumberg (USA) and Daniel Carlton Gaidusek (USA) - for the discovery of new mechanisms for the emergence and spread of infectious diseases.
1978. Daniel Nathans (USA), Hamilton Smith (USA) and Werner Arber (Switzerland) - for the discovery of restriction enzymes and work on the use of these enzymes in molecular genetics.
1979. Allan McLeod Carmack (USA) and Godfrey Newbold Hounsfield (Great Britain) - for the development of the axial tomography method.
1980. Baruch Benacerraf (USA), Jean Dosset (France) and George Davis Snell (USA) - for their discoveries of genetically determined cell surface structures that regulate immunological reactions.
1981. Roger Wolcott Sperry (USA) - for the discovery of the functional specialization of the cerebral hemisphere and David Hunter Huebel (USA) and Torsten Niels Wiesel (USA) - for discoveries concerning information processing in the visual system.
1982. Sune Bergstrom (Sweden), Bengt Samuelson (Sweden) and John Robert Vane (Great Britain) - for their work on the isolation and study of prostaglandins and related biologically active substances.
1983. Barbara McClintock (USA) - for the discovery of migratory elements (mobile genes) of the genome.
1984. Nils Kai Jerne (Great Britain) - for the development of the theory of the idiotypic network and Cesar Milstein (Argentina) and Georg Koehler (Germany) - for the development of the hybridoma technique.
1985. Michael Stuart Brown (USA) and Joseph Leonard Goldstein (USA) - for discovering the mechanism of regulation of cholesterol metabolism in animals and humans.
1986. Stanley Cohen (USA) and Rita Levi-Montalcini (Italy) - for studies of factors and mechanisms of growth regulation of cells and animal organisms.
1987. Suzumu Tonegawa (Japan) - for the discovery of the genetic basis for the formation of the variational richness of antibodies.
1988. Gertrude Elion (USA) and George Herbert Hitchings (USA) - for the development of new principles for the creation and use of a number of drugs (antiviral and antitumor).
1989. John Michael Bishop (USA) and Harold Eliot Varmus (USA) - for fundamental research on carcinogenic tumor genes.
1990. Edward Thomas Donnall (USA) and Joseph Edward Murray (USA) - for their contribution to the development of transplant surgery as a method of treating diseases (bone marrow transplantation and suppression of the recipient's immunity to prevent transplant rejection).
1991. Erwin Neuer (Germany) and Bert Zakman (Germany) - for their work in the field of cytology, opening up new possibilities for studying cell function, understanding the mechanisms of a number of diseases and developing special drugs.
1992. Edwin Krebs (USA) and Edmond Fisher (USA) - for the discovery of reversible protein phosphorylation as a regulatory mechanism of cellular metabolism.
1993. Roberts R., Sharpe F. (USA) - for the discovery of the discontinuous structure of the gene
1994. Gilman A., Rodbell M. (USA) - for the discovery of mediator proteins (G-proteins) involved in the transmission of signals between cells and within cells, and elucidation of their role in the molecular mechanisms of a number of infectious diseases (cholera, whooping cough and etc.)
1995. Wieschaus F., Lewis E. B. (USA), Nusslein-Folard H. (Germany) - for the study of genetic regulation of the early stages of embryonic development.
1996. Doherty P. (Australia), Zinkernagel R. (Switzerland) - for the discovery of the mechanism of recognition by cells of the body's immune system (T-lymphocytes), cells infected with a virus.
1997. Stanley Prusiner (USA) - for his contribution to the study of the pathogen that causes spongiform encephalopathy, or "mad cow disease", in cattle.
1998. Roberta Furchgott (USA), Luis Ignarro (USA) and Ferid Murad (USA - for the discovery of "nitric oxide as a signaling molecule in the cardiovascular system".
2000. Arvid Karlsson (Sweden), Paul Greengard (USA) and Eric Kandel (USA) - for studies of the human nervous system, which made it possible to understand the mechanism of the occurrence of neurological and mental diseases and create new effective drugs.
2001 - Leland Hartwell, Timothy Hunt, Paul Nurse - "Discovery of key regulators of the cell cycle."
2002 - Sydney Brenner, Robert Horwitz, John Salston - "for their discoveries in the field of genetic regulation of the development of human organs."
2003 - Paul Lauterbur, Peter Mansfield - "For the invention of the method of magnetic resonance imaging."
2004 - Richard Axel, Linda Buck - "for their research on olfactory receptors and the organization of the olfactory organ system."
2005 - Barry Marshall, Robin Warren - "for their work on the influence of the bacterium Helicobacter pylori on the occurrence of gastritis and gastric and duodenal ulcers."
2006 - Andrew Fire, Craig Mello - "for the discovery of RNA interference - the effect of quenching the activity of certain genes."
2007 - Mario Capecci, Martin Evans, Oliver Smithies - "For their discovery of the principles for introducing specific gene modifications in mice using embryonic stem cells."
2008 - Harald zur Hausen, For the discovery human papillomavirus causing cervical cancer.” Françoise Barre-Sinussi and Luc Montagnier. For the discovery of HIV.
In 2009, American scientists Elizabeth Blackburn, Carol Greider and Jack Szostak were awarded the Nobel Prize in Physiology or Medicine for their discovery of the telomere protection mechanism for chromosomes. Them scientific work is of great importance for understanding the aging process and finding new ways to treat cancer.
2010 in Physiology and Medicine awarded 85-year-old scientist from the UK Robert G. Edwards (Robert G. Edwards), who developed in 1978 the technology of artificial in vitro fertilization (in vitro fertilization - IVF). Over the past twenty years, more than four million people have been born thanks to this technology.
2011. Ralph Steinman, "for their discovery of dendritic cells and their implications for adaptive immunity."
Jules Hoffman, Bruce Boettler "for their work on the activation of innate immunity"
2012. John Gurdon, Shinya Yamanaka "For his work in developmental biology and induced stem cell production."
In 2016, the Nobel Committee awarded the Physiology or Medicine Prize to Japanese scientist Yoshinori Ohsumi for discovering autophagy and deciphering its molecular mechanism. Autophagy is a process of recycling spent organelles and protein complexes; it is important not only for the economical management of the cellular economy, but also for the renewal of the cellular structure. Deciphering the biochemistry of this process and its genetic basis suggests the possibility of controlling and managing the entire process and its individual stages. And this gives researchers obvious fundamental and applied perspectives.
Science rushes forward at such an incredible pace that the non-specialist does not have time to realize the importance of the discovery, and the Nobel Prize is already awarded for it. In the 80s of the last century, in biology textbooks, in the section on the structure of the cell, one could learn, among other organelles, about lysosomes - membrane vesicles filled with enzymes inside. These enzymes target the breakdown of various large biological molecules into smaller blocks (it should be noted that at that time our biology teacher did not yet know why lysosomes were needed). They were discovered by Christian de Duve, for which he was awarded the Nobel Prize in Physiology or Medicine in 1974.
Christian de Duve and colleagues separated lysosomes and peroxisomes from other cellular organelles using a then new method - centrifugation, which allows particles to be sorted by mass. Lysosomes are now widely used in medicine. For example, targeted drug delivery to damaged cells and tissues is based on their properties: a molecular drug is placed inside the lysosome due to the difference in acidity inside and outside it, and then the lysosome, equipped with specific labels, is sent to the affected tissues.
Lysosomes are illegible by the nature of their activity - they break up any molecules and molecular complexes into their constituent parts. Narrower "specialists" are proteasomes, which are aimed only at the breakdown of proteins (see:, "Elements", 11/05/2010). Their role in the cellular economy can hardly be overestimated: they monitor the enzymes that have served their time and destroy them as needed. This period, as we know, is defined very precisely - exactly as much time as the cell performs a specific task. If the enzymes were not destroyed upon its completion, then the ongoing synthesis would be difficult to stop in time.
Proteasomes are present in all cells without exception, even in those where there are no lysosomes. The role of proteasomes and the biochemical mechanism of their work was investigated by Aaron Ciechanover, Avram Hershko and Irwin Rose in the late 1970s and early 1980s. They discovered that the proteasome recognizes and destroys those proteins that are labeled with the protein ubiquitin. The binding reaction with ubiquitin comes at the expense of ATP. In 2004, these three scientists received the Nobel Prize in Chemistry for their research on ubiquitin-dependent protein degradation. In 2010, looking through school curriculum for gifted English children, I saw a row of black dots in the picture of the structure of the cell, which were labeled as proteasomes. However, the school teacher at that school could not explain to the students what it is and what these mysterious proteasomes are for. With lysosomes in that picture, no questions arose.
Even at the beginning of the study of lysosomes, it was noticed that parts of cell organelles are enclosed inside some of them. This means that in lysosomes, not only large molecules are disassembled, but also parts of the cell itself. The process of digesting one's own cellular structures is called autophagy - that is, "eating oneself." How do parts of cell organelles get into the lysosome containing hydrolases? Back in the 80s, he began to deal with this issue, who studied the structure and functions of lysosomes and autophagosomes in mammalian cells. He and his colleagues showed that autophagosomes appear in mass in cells if they are grown on a nutrient-poor medium. In this regard, a hypothesis has arisen that autophagosomes are formed when a reserve source of nutrition is needed - proteins and fats that are part of extra organelles. How are these autophagosomes formed, are they needed as a source of additional nutrition or for other cellular purposes, how do lysosomes find them for digestion? All these questions in the early 1990s had no answers.
Taking on independent research, Osumi focused his efforts on the study of yeast autophagosomes. He reasoned that autophagy should be a conserved cellular mechanism, hence, it is more convenient to study it on simple (relatively) and convenient laboratory objects.
In yeast, autophagosomes are located inside vacuoles and then disintegrate there. Various proteinase enzymes are engaged in their utilization. If the proteinases in the cell are defective, then autophagosomes accumulate inside the vacuoles and do not dissolve. Osumi took advantage of this property to obtain a culture of yeast with an increased number of autophagosomes. He grew cultures of yeast on poor media - in this case, autophagosomes appear in abundance, delivering a food reserve to the starving cell. But his cultures used mutant cells with inactive proteinases. So, as a result, cells quickly accumulated a mass of autophagosomes in vacuoles.
Autophagosomes, as follows from his observations, are surrounded by single-layer membranes, which can contain a wide variety of contents: ribosomes, mitochondria, lipid and glycogen granules. By adding or removing protease inhibitors to wild cell cultures, one can increase or decrease the number of autophagosomes. So in these experiments it was demonstrated that these cell bodies are digested with the help of proteinase enzymes.
Very quickly, in just a year, using the method of random mutation, Ohsumi identified 13-15 genes (APG1-15) and the corresponding protein products involved in the formation of autophagosomes (M. Tsukada, Y. Ohsumi, 1993. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae). Among colonies of cells with defective proteinase activity, he selected under a microscope those in which there were no autophagosomes. Then, cultivating them separately, he found out which genes they had corrupted. It took his group another five years to decipher, as a first approximation, the molecular mechanism of these genes.
It was possible to find out how this cascade works, in what order and how these proteins bind to each other, so that the result is an autophagosome. By 2000, the picture of membrane formation around damaged organelles to be processed became clearer. The single lipid membrane begins to stretch around these organelles, gradually surrounding them until the ends of the membrane approach each other and fuse to form the double membrane of the autophagosome. This vesicle is then transported to the lysosome and fuses with it.
APG proteins are involved in the process of membrane formation, analogs of which Yoshinori Ohsumi and colleagues found in mammals.
Thanks to the work of Osumi, we have seen the whole process of autophagy in dynamics. The starting point of Osumi's research was the simple fact of the presence of mysterious small bodies in the cells. Now researchers have the opportunity, albeit hypothetical, to control the entire process of autophagy.
Autophagy is necessary for the normal functioning of the cell, since the cell must be able not only to renew its biochemical and architectural economy, but also to utilize the unnecessary. There are thousands of worn-out ribosomes and mitochondria, membrane proteins, spent molecular complexes in the cell - all of them need to be economically processed and put back into circulation. This is a kind of cellular recycling. This process not only provides a certain economy, but also prevents the rapid aging of the cell. Disruption of cellular autophagy in humans leads to the development of Parkinson's disease, type II diabetes, cancer, and some disorders associated with old age. Controlling the process of cellular autophagy obviously has great prospects, both in fundamental and applied terms.
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The 2018 Nobel Prize in Physiology or Medicine was awarded to James Ellison and Tasuku Honjo for their developments in cancer therapy by activating the immune response. The announcement of the winner is broadcast live on the website of the Nobel Committee. More information about the merits of scientists can be found in the press release of the Nobel Committee.
Scientists have developed fundamentally new approach to cancer therapy, different from the pre-existing radiotherapy and chemotherapy, which is known as "checkpoint inhibition" of immune cells (a little about this mechanism can be read in our dedicated to immunotherapy). Their research is focused on how to eliminate the suppression of the activity of cells of the immune system by cancer cells. Japanese immunologist Tasuku Honjo from the University of Kyoto discovered the PD-1 (Programmed Cell Death Protein-1) receptor on the surface of lymphocytes, the activation of which leads to the suppression of their activity. His American colleague James Allison from the Anderson Cancer Center of the University of Texas showed for the first time that an antibody blocking the CTLA-4 inhibitory complex on the surface of T-lymphocytes, introduced into the body of animals with a tumor, leads to the activation of the antitumor response and tumor reduction.
The research of these two immunologists has led to the emergence of a new class of anti-cancer drugs based on antibodies that bind to proteins on the surface of lymphocytes or cancer cells. The first such drug, ipilimumab, an antibody that blocks CTLA-4, was approved in 2011 for the treatment of melanoma. An anti-PD-1 antibody, nivolumab, was approved in 2014 against melanoma, lung, kidney, and several other types of cancer.
“Cancer cells, on the one hand, are different from our own, on the other hand, they are. The cells of our immune system recognize this cancer cell, but do not kill it, - explained N+1 Professor of the Skolkovo Institute of Sciences and Technology and Rutgers University Konstantin Severinov. - The authors, among other things, discovered the PD-1 protein: if this protein is removed, then immune cells begin to recognize cancer cells and can kill them. This is the basis of cancer therapy, which is now widely used even in Russia. Such PD-1 inhibitory drugs have become an essential component of the modern arsenal of cancer control. He is very important, without him it would be much worse. These people really gave us new way cancer control - people live because there are such therapies.
Oncologist Mikhail Maschan, deputy director of the Dima Rogachev Center for Pediatric Hematology, Oncology and Immunology, says immunotherapy has revolutionized cancer treatment.
“In clinical oncology, this is one of the biggest events in history. We are just now beginning to reap the benefits that this type of therapy has brought, but the fact that it has turned the situation in oncology became clear about a decade ago - when the first clinical results of the use of drugs created on the basis of these ideas appeared,” Maschan said. in conversation with N+1.
With a combination of checkpoint inhibitors, long-term survival, that is, actual recovery, can be achieved in 30-40 percent of patients with certain types of tumors, in particular melanoma and lung cancer, he says. He noted that new developments based on this approach will appear in the near future.
“This is the very beginning of the journey, but there are already many types of tumors - both lung cancer and melanoma, and a number of others, in which therapy has shown effectiveness, but even more - in which it is only being studied, its combinations with conventional types of therapy are being studied. This is the very beginning, and a very promising start. The number of people who have survived thanks to this therapy is already measured in tens of thousands,” Maschan said.
Every year, in the run-up to the announcement of the winners, analysts try to guess who will be awarded the prize. This year, Clarivate Analytics, which traditionally makes predictions based on the citation of scientific papers, included in the Nobel List Napoleone Ferrara, who discovered a key factor in the formation of blood vessels, Minoru Kanehis, who created the KEGG database, and Salomon Snyder, who worked on receptors. for key regulatory molecules in nervous system. It is interesting that the agency indicated James Ellison as a possible Nobel Prize winner in 2016, that is, in his regard, the forecast came true pretty soon. Whom the agency reads as laureates in other Nobel disciplines - physics, chemistry and economics, you can find out from our blog. In literature, this year the award will be presented.
Daria Spasskaya