Translated material
Nobel Prizes - 2018
Laser breakthroughs
The Nobel Prize in Physics of 2018, the award of which was announced on October 2, is commented by Kand for the TRV-hunger. physical. sciences, Art. scientific. sore. Institute of Applied Physics of the Russian Academy of Sciences, author of the popular science channel in the Telegram @physh messenger Artyom Korzhimanov .
As usual in early October, the world last week recognized the names of the next Nobel Prize laureates. In physics, it was divided between three scientists. Half went to Arthur Ashkin for the invention of laser tweezers, and also divided the equal to Gerard Mouro and Donna Strickland for the method of generating high -intensity ultra -short optical impulses.
Despite the fact that both awards are united by the wording “for research in the field of laser physics”, its two halves were awarded for two practically no intersecting achievements, which had the equally large influence on other areas of science.
Laser , or optical , tweezers - this is a device that allows you to manipulate microscopic objects using laser bundles. The fact that light can move objects, people know at least from the beginning of the 20th century - it was then that Peter Lebedev experimentally proved the existence of light pressure. However, there is another opportunity for the movement of particles by light. If the particle is transparent, then the light in it can be refracted, changing the direction of its movement. But, since the light transfers the impulse, then, roughly speaking, according to the third law of Newton, or, more correctly, from the law of preservation of impulse, it follows that the particle should begin to move in the opposite direction. Usually the forces arising in this way are compensated and the particle is motionless, however, if the intensity of light is distributed very heterogeneous, then on the one hand the particle will be refracted more than the light, and on the other, less, which will lead to the emergence of the resulting force directed towards greater intensity.
Pioneer work in this area was performed by Arthur Eshkin back in the mid-1980s. Since then, laser tweezers have turned into a routine tool and provided a real breakthrough in many applications in which it is necessary to control the position of microscopic objects. First of all, and this is separately emphasized in the formulation of the Nobel Committee - we are talking about biology and medicine and manipulations with individual cells.
It is worth noting that Eshkin became the oldest Nobel Prize in history. At the time of award, he turned 96 years old.
The work of Gerara Muru and Donna Strikland is associated with the task of achieving record high laser radiation capacities. Actually, since the invention of Lazer in 1960, this direction was one of the main in the field of laser physics, and by the end of the 1960s, impulses of several gigavatts were obtained.
Such high power was achieved with relatively small energy costs due to the development of short pulses generation methods. The characteristic duration of the pulse was several nanoseconds (1 nanosecond = 10-9 seconds), so with a power of 1 GW they had energy only a few joules-less than that of bricks that fell out of their hands.
At a gigavatte power level, however, a problem arose. Laser radiation began to destroy those crystals in which its strengthening occurred. Naturally, this was an increase in the transverse sizes of crystals and the reduction at the point of radiation of a large number of laser impulses. The obvious problem was that it was extremely difficult to grow optical quality crystals with a diameter of more than a dozen centimeters, and the reduction at the point of dozens of laser rays required large and complex synchronization systems.
Nevertheless, within the framework of the laser thermonuclear synthesis program, by 1984, a 10-channel NOVA system of 50 TVT and with an impressive 10 kJ power system was created in the Liverrand National Laboratory (USA).
It is at this moment that a researcher at the University of Rochester, who came from France, J. Muru and his graduate student D. Strikland release an article in which they offer a fundamentally different approach to achieving record -based high capacities. The method they proposed is the name "Strengthening the Chirped Pulse Amplification, CPA), from the English" chirp " - the sequence.
The impulses are called the chirpapered, in which their components are spaced in time: at first there are lower frequencies, then higher ones. Trill of some birds are similarly arranged: they first make lower sounds, gradually increasing their tone. In Russian-speaking literature, such impulses are commonly called frequency-modified.
The main idea of the method is to lengthen the enhanced impulses without changing their frequency composition. This is achieved due to their passage in systems with dispersion, in which the speed of the spread of light depends on its frequency. The impulse that has passed through such a system acquires a “chirus” and becomes longer. Examples of frequently used dispersing systems are a pair of prisms or a pair of diffraction grates.
Chirping allows you to increase the duration of pulses by hundreds of thousands of times. The power of the impulse also falls in proportion to elongation, which allows you to continue its strengthening in crystals. In this case, the frequency composition of the pulse is preserved, which allows you to further compress the pulse back, passing it through the dispersing system, the reverse of the initial one.
The fact that when reflected materials are able to withstand significantly higher radiation intensity are critical than when it spreads inside the same material. Therefore, the dispersing system compressing the impulse is performed on the basis of diffraction grates that work on reflection.
This method (CPA) made it possible to increase power not by increasing energy, but by decreasing the duration of pulses. Almost simultaneously with the invention of the method, a new laser material was discovered-titanium-sapfire (aluminum oxide, doped by Titan ions), which possessed a sufficient width of the amplification strip in order to provide pulses generation of only 20-30 femo-sedes.
Such lasers of ultra -high power and over -short duration turned out to be compact and relatively inexpensive. This led to their wide distribution: if before that, the teravat systems were available only to laboratories of the national level, now even a small university laboratory could afford them.
By the way, one of the channels of the NOVA system, which was discussed at first, was equipped with the CPA system, and in 1996 a completely fantastic power of 1.25 Petavatt was reached on it. The era of petavat lasers began. The record capacity of laser impulses at the moment - 5 PVT - was reached in 2016 by the Chinese laser system SULF (SuperinTense Ultrafast Laser Facility).
For further growth in pulses, scientists plan to return to the old idea: to reduce at the point the radiation of several petavat lasers. Three such projects are being discussed now - in Europe, China and Russia. The Russian project Xcels was prepared at the Institute of Applied Physics of the Russian Academy of Sciences and formally supported in 2012 by the Russian government under the program “Megascience Projects”. It was initiated and promoted by the current president of the Academy of Sciences Alexander Sergeyev, then the deputy. Director of IPF RAS.
J. Muru, by the way, also put his hand to this project, since in 2010-2014 he headed a laboratory at the Nizhny Novgorod State University as part of megagran projects. However, the financing of XCels, unfortunately, has not yet begun.
Petavatt lasers are now used mainly to generate beams of high -energy particles: electrons, protons and other ions. Acting as an alternative to traditional accelerators operating on the basis of radio frequency resonators, super -powerful lasers allow, for example, to speed up electrons to several gigaelectron volts at a distance of about a few centimeters, while the traditional methods would need a vacuum pipe with a length of hundreds of meters. The prospective use of such electrons is the generation of super-icing x-ray radiation, with which you can conduct a phase-contract radiography in demand in medicine.
Achievements in the field of laser acceleration of protons and ions are much more modest: the current energy record for obtained protons does not exceed 100 megaelectron volts, while traditional accelerators allow you to receive gigs and even teraelectron volts. A little faster protons-with an energy of about 200-400 MeV-could be used for proton radiation therapy. Now they find their application mainly for protonography. In addition, protons manage to effectively convert into neutrons, creating an super -thawed source for neutronography and neutron physics. Such sources can potentially help, for example, to deal with a poorly studied R-process (the rapid process of capturing neutrons), which, apparently, ensured the presence of elements in our universe harder than Nickel.
Finally, at a power of tens of petavatt, an exciting perspective, the opportunity to study the quantum properties of a vacuum looks. The radiation intensity in this case will generate high-energy gamma-photons, which immediately decaying into electron-positive pairs. During the times of the less optical period, the density of the formed plasma can reach incredible values up to 1026 cm3. Such systems will allow the routine way to study quantum electrodynamics in a highly non -linear interaction mode.
CPI therapy: Ahead is a long and difficult path
On October 1, 2018, the Nobel Prize in Physiology and Medicine was awarded to two immunologists: 70-year-old professor at the University of Tehas (USA) James P. Allison and 76-year-old professor of Kyoto University (Japan) Tasuku Hondzo (Tasuku Honjo) Cancer therapy by inhibiting negative immune regulation. ”
Dmitry Chudakov, head, talks about the problems of immunotherapy, head. Department of the genomes of adaptive immunity IBH RAS, associated professor Skoltha, head of the laboratory of genomes of adaptive anti -abnormal immunity of the Volga Research University, head. Department of Molecular Technologies RNIMU named after N.I. Pirogov.
The idea that in many cases the patient’s immune system, having received correct incentives and tips, is fundamentally capable of destroying the tumor, has been formed over the past few decades. Nevertheless, until recently, the success in the immunotherapy of cancer remained relatively incredible.
New opportunities and hopes opened with the receipt of antibodies, selectively recognizing and suppressing the “control points” of the immune response-receptor molecules that normally inhibit excessive proliferation and activation of T-lymphocytes, such as PD-1 and CTLA-4.
Such receptors also suppress the activity of the so-called cytotoxic T-lymphocytes-cells that can specifically destroy our own cells-infected or malignant. On the one hand, this mechanism is necessary to prevent the destructive activity of the immune system and the development of autoimmune diseases. On the other hand, the same mechanism often limits the necessary antitumor response.
The antibody to the CTLA-4 (IPilimumab) was the first such drug, in 2011 approved to clinical use for malignant melanoma. It is curious that the main mechanism of action by IPILIMUMAB, as shown by later studies, turned out to be slightly different as the developers suggest.
The fact is that IPILIMUMAB is a cytotoxic antibody (i.e., capable of leading to the destruction of marked cells), and its injection leads to the elimination of subtype lymphocytes that most pronounced CTLA-4 on its surface, namely regulatory T-lymphocytes (TREG). Since the main Treg function is to suppress excessive answers of effector T-lymphocytes, their elimination leads to a pronounced activation of cytotoxic, including antitumor T-cell response.
However, such total activation is associated with severe autoimmune effects, which significantly limits the use of iPilimumab. Currently, various options for non-cytotoxic antibodies to CTLA-4 are underway, the effect of which can be less pronounced, but more sparing from the point of view of caused autoimmune reactions and can significantly help in case of a successful combination with other approaches.
Despite the fact that the mechanism of action of the first approved CPI turned out to be different from the planned, the first successes achieved opened the way for the development of a whole palette of new immunotherapeutic approaches.
In 2014, the first antibody to PD1 (Pembrolizumab, commercial name Keytruda) was approved for therapy of malignant melanoma. Clinical studies of Anti-PD1 Checkmate-066 and Keynote-006 (with a reservation-conducted by interested pharmaceutical companies) for patients with inoperative or metastasis melanoma (with a reservation that did not receive therapy) showed more than 70 percent survival within one year.
Three-year survival reaches 40% (for comparison: before CPI therapy, this indicator did not exceed 10%). For 10-15% of patients, it is possible to achieve a complete long-term cure. In general, for most of the patients from among those who overcome the two -year line, the forecast remains positive.
Currently, the use of six different CPIs (antibodies to CTLA-4, PD-1 and PD-L1-Landa PD1) and their combinations with other approaches are recommended for certain indications for 11 various cancer diseases. The greatest efficiency of anti-PD1-therapy is indicated for melanoma, non-coclucket lung cancer, bladder cancer, and triple negative breast cancer.
Currently, more than 250 clinical tests of new immunotherapeutic approaches, such as new oncocks, CPI, CAR-T-therapy and oncolytic viruses, are taking place. There are more than 700 tests of combinations of anti-PD-1 or anti-PD-L1 drugs with other therapies, and a number of combinational approaches demonstrates encouraging results. In particular, combinations of anti-PD-1/ PD-L1-therapy and targeted therapy, such as BRAF and/ or MEK inhibitors for patients with a melanoma carrying a BRAF mutation, look promising.
It must be understood that the relationship between the cells of the tumor, micro -infection and the immune system is very complex and heterogeneous. Evolutionary tumor cells select a variety of methods of inhibiting or leaving the immune response, not all of which are known and understandable today. Clinicists, immunologists, molecular biologists, bio -formatics and programmers have to agree on a long and difficult path to get a long and difficult path before we learn to choose the right therapeutic combination for each patient.
Nevertheless, the 2018 Nobel Prize for Physiology and Medicine, deservedly awarded to the founders of CPI therapy-James Ellison (showed the inhibitory function of CTLA-4, 1987) and Tasuku Khondzo (opening the PD1, 1992 molecule)-marks the successful beginning of this path.
"I think there will be no absolute victory over cancer"
Ravshan Ataullakhanov , Dot. honey. sciences, professor of Moscow State University. Lomonosov, head of the department and laboratory of the Institute of Immunology of the Federal Medical and Biological Agency, answered questions from the Trv-hunger.
- Did the Nobel Prize of this year surprise you?
- No, I did not surprise. A couple of years ago, the United States actively discussed the possibility of awarding the Nobel Prize James Ellison. James and Tasuku Hondzo are worthy scientists who made a worthy discovery. Its strength is that it led to the creation of new methods of saving patients with cancer.
- What are the prospects, in your opinion, now the immunotherapy of cancer has?
- Cancer immunotherapy has great prospects. This approach has undoubted advantages over other treatment methods. He uses the “internal doctor” (read “immune defense”). For decades, this doctor successfully prevents the occurrence of malignant neoplasms in the human body. Tumors arise when the immune defense united. This happens due to a variety of reasons - from stress to aging.
Therefore, it is difficult to come up with something more natural, more perfect than the effective mechanism of the fight against malignant mutant cells created by nature. Therefore, I believe in the great prospects of immunotherapy, the meaning of which is in the use of human immunity and its instruments (molecules and cells) to combat a malignant tumor.
-Will this disease ever win humanity?
- No one knows the future. Me too. I think there will be no absolute victory, but the treatment will become effective in the sense that patients will live for a long time with the normal quality of life. This is the case when the quantity matters. Пусть неабсолютное по эффективности лечение остановит рак на 30–40 лет. Это и есть желанный результат.
Почему я думаю, что абсолютного эффекта не будет? Потому что победишь одну опухоль — а через какое-то время возникнет другая и т. д. Сам процесс возникновения опасных мутантных клеток и возможность каких-то из них «проскочить» иммунный контроль вряд ли куда-то исчезнут. Это плата за большое количество клеток, составляющих наш организм, и за их обновление (размножение), при котором возникают ошибки в геноме клеток, следовательно, с определенной частотой рождаются опасные мутанты.
Talked by Natalia Demina
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Нобелевская премия по химии за 2018 год досталась троим ученым. Половину премии получит американская исследовательница Фрэнсис Арнольд (Frances Arnold) «за направленную эволюцию ферментов», вторую половину поровну поделят Джордж Смит (George Smith) из США и сэр Грегори Уинтер (Gregory Winter) из Великобритании «за работы по фаговому дисплею пептидов и антител».
old.nobelprize.org/che-press.pdf
Нобелевская премия по экономике (более точно — премия Государственного банка Швеции памяти Альфреда Нобеля) за 2018 год присуждена американцам Уильяму Нордхаусу (William Nordhaus) «за включение изменений климата в долгосрочный макроэкономический анализ» и Полу Ромеру (Paul Romer) «за включение технологических инноваций в долгосрочный макроэкономический analysis".