The Nobel Prize in Medicine was awarded for cancer immunotherapy. Prize in Physiology or Medicine Nobel Laureates in Physiology or Medicine

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 are aimed at splitting various large biological molecules into smaller units (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, while looking through a school curriculum for gifted English children, I saw a row of black dots in a picture of the structure of a 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.

In early October, the Nobel Committee summed up the work for 2016 in various areas of human activity that brought the greatest benefit and named the Nobel Prize nominees.

You can be skeptical about this award as much as you like, doubt the objectivity of the choice of laureates, question the value of the theories and merits put forward for nomination ... . All this, of course, has a place to be ... Well, tell me, what is the value of the peace prize awarded, for example, to Mikhail Gorbachev in 1990 ... or the similar award to American President Barack Obama for peace on the planet, which made even more noise in 2009 🙂 ?

Nobel Prizes

And this year 2016 was not without criticism and discussions of the new awardees, for example, the world ambiguously accepted the award in the field of literature, which went to the American rock singer Bob Dylan for his poems to songs, and the singer himself reacted even more ambiguously to the award, reacting for the award after only two weeks ....

However, regardless of our philistine opinion, this high the award is considered the most prestigious award in the scientific world, has been living for more than a hundred years, has hundreds of awardees, a prize fund of millions of dollars.

The Nobel Foundation was founded in 1900 after the death of his testator Alfred Nobel- an outstanding Swedish scientist, academician, Ph.D., inventor of dynamite, humanist, peace activist and so on ...

Russia in the list of awardees 7th place, has in the entire history of awards 23 nobelists or 19 awards(there are groups). The last Russian to be awarded this high honor was Vitaly Ginzburg in 2010 for his discoveries in the field of physics.

So, the awards for 2016 are divided, the awards will be presented in Stockholm, the total size of the fund changes all the time and the size of the award changes accordingly.

Nobel Prize in Physiology or Medicine 2016

Few ordinary people, far from science, delve into the essence of scientific theories and discoveries that deserve special recognition. And I'm one of those :-) . But today I want to dwell on one of the awards for this year in a little more detail. Why medicine and physiology? Yes, everything is simple, one of the most intense sections of my blog “Be healthy”, because the work of the Japanese interested me and I understood a little about its essence. I think the article will be of interest to people who adhere to a healthy lifestyle.

So, the Nobel Prize winner in the field of Physiology and Medicine for 2016 became 71 year old Japanese Yoshinori Osumi(Yoshinori Ohsumi) is a molecular biologist at Tokyo University of Technology. The topic of his work is “Discovery of the mechanisms of autophagy”.

autophagy in Greek, “self-eating” or “self-eating” is a mechanism for processing and utilizing unnecessary, obsolete parts of the cell, which is performed by the cell itself. Simply put, the cell eats itself. Autophagy is inherent in all living organisms, including humans.

The process itself has been known for a long time. The scientist’s research, conducted back in the 90s of the century, opened and allowed not only to understand in detail the importance of the autophagy process for many physiological processes occurring inside a living organism, in particular, when adapting to hunger, response to infection, but also to identify the genes that trigger this process.

How is the process of cleansing the body? And just like we clean up our garbage at home, only automatically: cells pack all unnecessary trash, toxins into special “containers” - autophagosomes, then move them to lysosomes. Here, unnecessary proteins and damaged intracellular elements are digested, while fuel is released, which is supplied to nourish cells and build new ones. It's that simple!

But what's most interesting about this study is that autophagy is triggered faster and more powerful when the body experiences it, and especially when it's FASTING.

The discovery of the Nobel Prize winner proves that religious fasting and even periodic, limited hunger are still useful for a living organism. Both of these processes stimulate autophagy, cleanse the body, relieve the burden on the digestive organs, and thereby save from premature aging.

Disruptions in autophagy processes lead to diseases such as Parkinson's, diabetes, and even cancer. Doctors are looking for ways to deal with them with medication. Or maybe you just need not be afraid to expose your body to health fasting, thereby stimulating the renewal processes in cells? At least occasionally...

The work of the scientist once again confirmed how amazingly subtle and clever our body is, how far not all the processes in it are known...

The well-deserved prize of eight million Swedish crowns (932 thousand US dollars) will be received by the Japanese scientist along with other awardees in Stockholm on December 10, the day of Alfred Nobel's death. And I think it's well deserved...

Were you even slightly interested? And how do you feel about such conclusions of the Japanese? Do they make you happy?

The Nobel Committee has announced the winners of the 2017 Physiology or Medicine Prize today. This year the award will once again travel to the US, with Michael Young of the Rockefeller University in New York, Michael Rosbash of Brandeis University and Geoffrey 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 the study of the sleep-wake cycle, as well as 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 area, who discovered REM sleep (REM - rapid eye movement, rapid sleep phase), generally received only a PhD degree for his achievement. It is not surprising that in numerous forecasts (we wrote about them in our note) there were any names and any research topics, but not those that attracted the attention of the Nobel Committee.

What was the award for?

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?”.

Geoffrey Hall, Michael Rosbash, Michael Young

Circa diem translated from Latin as "around the day". It so happened that we live on planet Earth, where day is replaced by night. And in the course of adapting to different conditions of day and night, organisms developed an internal biological clock - the rhythms of the biochemical and physiological activity of the organism. It was only in the 1980s that it was possible to show that these rhythms had an exclusively internal nature 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 1960–1970s by Seymour Benzer and Ronald Konopka, who studied mutant lines of fruit flies with different circadian rhythms: in wild-type flies, circadian rhythm fluctuations had a period of 24 hours, in some mutants - 19 hours, in others - 29 hours, and the third had no rhythm at all. It turned out that rhythms are regulated by the gene PER - period. The next step, which helped to understand how such fluctuations in the circadian rhythm are created and maintained, was taken by the current laureates.

Self-adjusting clockwork

Geoffrey Hall and Michael Rosbash suggested that the gene encoded period PER protein blocks the work of its own gene, and such a 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 24 hours of fluctuation. When the gene is active, 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 the activity of a gene, the protein needs to get into the nucleus of the cell, where the genetic material is stored. Jeffrey Hall and Michael Rosbash showed that the PER protein accumulates overnight in the nucleus, but did not understand how it managed to get there. In 1994, Michael Young discovered the second circadian rhythm gene, timeless(English "timeless"). It codes for the TIM protein, which is essential for our internal clock to function properly. In his elegant experiment, Young demonstrated that only by binding to each other, TIM and PER paired can 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 appearance of oscillations, but it was not clear what controls their frequency. Michael Young found another gene double time. It contains the DBT protein, which can delay the accumulation of the PER protein. This is how fluctuations 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.

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 to Emil von Behring for the development of a serum therapy for diphtheria. In total, the prize has been awarded 108 times throughout history, in nine cases: in 1915, 1916, 1917, 1918, 1921, 1925, 1940, 1941 and 1942, the prize was not awarded.

Between 1901 and 2017, the prize was awarded to 214 scientists, a dozen of whom are women. So far, there has not been a case of someone receiving a prize in medicine twice, although there have been cases when an already acting laureate was nominated (for example, our Ivan Pavlov). Excluding 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), the oldest was the 1966 laureate Peyton Rose (award for the discovery of oncogenic viruses, age 87 years).

According to the website of the Nobel Committee, by studying the behavior of fruit flies in different phases of the day, researchers from the United States were able to look inside the biological clock of living organisms and explain the mechanism of their work.

Geoffrey Hall, a 72-year-old geneticist from the University of Maine, his 73-year-old colleague Michael Rosbash of the private Brandeis University, and Michael Young, 69, of Rockefeller University, have figured out how plants, animals and people adapt to the change of day and night. Scientists have discovered that circadian rhythms (from the Latin circa - “about”, “around” and the Latin dies - “day”) are regulated by the 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 Geoffrey Hall, Michael Rosbash and Michael Young began researching the molecular biological nature of living organisms' internal clocks in 1984.

“The biological clock regulates behavior, hormone levels, sleep, body temperature and metabolism. Our well-being deteriorates if there is a discrepancy between the external environment and our internal biological clock - for example, when we travel across multiple time zones. Nobel laureates have 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 website says.

Top 10 Nobel Laureates in Physiology or Medicine

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

On the tenth line- Francis Crick, British molecular biologist who received the Nobel Prize in 1962 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", in other words, for the study of DNA.

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

In seventh place- Chinese pharmacologist Tu Yuyu. Together with William Campbell and Satoshi Omura in 2015, she received the Nobel Prize “for discoveries in the field of new ways to treat malaria”, or rather, for the discovery of artemisinin, an annual preparation from wormwood, which helps fight this infectious disease. Note that Tu Yuyou became the first Chinese woman to be awarded the Nobel Prize in Physiology or Medicine.

In fifth place in the list of the most popular Nobel laureates is the Japanese Yoshinori Ohsumi, the winner of the award in the field of physiology and medicine in 2016. He discovered the mechanisms of autophagy.

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

On the third place James Dewey Watson, an American biologist who received the award along with Francis Crick and Maurice Wilkins in 1952 for the discovery of the structure of DNA, is ranked among the Nobel Prize winners in Physiology or Medicine.

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

The Royal Swedish Academy has announced the first Nobel Prize winners for this year. The Physiology or Medicine Prize went to James Ellison and Tasuku Honjo. According to the wording of the Nobel Committee, the prize was awarded for "the discovery of anti-cancer therapy by suppressing negative immune regulation."

The discoveries that formed the basis of this scientific work were made back in the 1990s. James Ellison, who worked in California, studied an important component of the immune system - a protein that, like a brake, restrains the immune response mechanism. If the cells of the immune system are released from this brake, the body will be much more active in recognizing and destroying tumor cells. The Japanese immunologist Tasuku Honjo discovered another component of this regulatory system, which operates according to a slightly different mechanism. In the 2010s, the discoveries of immunologists formed the basis for effective cancer therapy.

The human immune system is forced to maintain a balance: it recognizes and attacks all proteins foreign to the body, but does not touch the body's own cells. This balance is especially delicate in the case of cancer cells: genetically they are no different from healthy cells in the body. The function of the CTLA4 protein that James Ellison worked with is to serve as an immune response checkpoint and prevent the immune system from attacking its own proteins. The PD1 protein, the subject of scientific interests of Tasuku Honjo, is a component of the "programmed cell death" system. Its function is also to prevent an autoimmune reaction, but it acts in a different way: it starts or controls the mechanism of cell death of T-lymphocytes.

Cancer immunotherapy is one of the most promising areas of modern oncology. It is based on pushing the patient's immune system to recognize and destroy cancer cells. The scientific discoveries of this year's Nobel laureates formed the basis of highly effective anticancer drugs that have already been approved for use. In particular, the Keytruda drug attacks the PD1 protein, the receptor for programmed cell death. The drug was approved for use in 2014 and is used to treat non-small cell lung cancer and melanoma. Another drug, ipilimumab, attacks the CTLA4 protein - the very "brake" of the immune system - and thereby activates it. This remedy is used in patients with advanced lung or prostate cancer, and in more than half of the cases it stops the further growth of the tumor.

James Ellison and Tasuku Honjo are the 109th and 110th recipients of the Nobel Prize in Medicine, which has been awarded since 1901. Among the laureates of previous years are two Russian scientists: Ivan Pavlov (1904) and Ilya Mechnikov (1908). Interestingly, Ilya Mechnikov received his award with the wording “For Works on Immunity”, that is, for achievements in the same field of biological science as the 2018 laureates.