Нобелевские лауреаты в области медицины
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Лауреаты Нобелевской премии в Великобритании Фрэнсис Крик Выполнила студентка группы Л31-1 Медицинского Колледжа №1 (Структурное Подразделение 1) Михайлова Евгения Александровна Москва , 2017Слайд 2
Francis Harry Compton Crick was born 8 Jule 1916 and raised in Weston Favell , then a small village near the English town of Northampton, in which Crick’s father and uncle ran the family’s boot and shoe factory . At an early age, Francis was attracted to science and what he could learn about it from books. As a child, he was taken to church by his parents. But by about age 12, he said he did not want to go anymore, as he preferred a scientific search for answers over religious belief . After the age of 14, he was educated at Mill Hill School in London (on scholarship), where he studied mathematics, physics, and chemistry with his best friend John Shilston . He shared the Walter Knox Prize for Chemistry on Mill Hill School's Foundation Day, Friday, 7 July 1933. He declared that his success was inspired by the quality of teaching he received whilst a pupil at Mill Hill . Early life and education
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At the age of 21, Crick earned a Bachelor of Science degree in physics from University College London. Crick had failed to gain a place at a Cambridge college, probably through failing their requirement for Latin. Crick began his PhD at UCL but was interrupted by WWII. He later became a PhD student and Honorary Fellow of Gonville and Caius College, Cambridge and mainly worked at the Cavendish Laboratory and the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge. He was also an Honorary Fellow of Churchill College, Cambridge and of University College, London.
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Post-World War II life and work In 1947, aged 31, Crick began studying biology and became part of an important migration of physical scientists into biology research. This migration was made possible by the newly won influence of physicists such as Sir John Randall, who had helped win the war with inventions such as radar. Crick had to adjust from the "elegance and deep simplicity" of physics to the "elaborate chemical mechanisms that natural selection had evolved over billions of years." He described this transition as, "almost as if one had to be born again .“ For the better part of two years, Crick worked on the physical properties of cytoplasm at Cambridge's Strangeways Research Laboratory, headed by Honor Bridget Fell, with a Medical Research Council studentship, until he joined Max Perutz and John Kendrew at the Cavendish Laboratory. The Cavendish Laboratory at Cambridge was under the general direction of Sir Lawrence Bragg , who had won the Nobel Prize in 1915 at the age of 25 .
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Research Crick was interested in two fundamental unsolved problems of biology: how molecules make the transition from the non-living to the living, and how the brain makes a conscious mind. He realized that his background made him more qualified for research on the first topic and the field of biophysics. It was at this time of Crick’s transition from physics to biology that he was influenced by both Linus Pauling and Erwin Schrödinger . It was clear in theory that covalent bonds in biological molecules could provide the structural stability needed to hold genetic information in cells. It only remained as an exercise of experimental biology to discover exactly which molecule was the genetic molecule . In Crick’s view, Charles Darwin’s theory of evolution by natural selection, Gregor Mendel’s genetics and knowledge of the molecular basis of genetics, when combined, revealed the secret of life. Crick had the very optimistic view that life would very soon be created in a test tube. However, some people (such as fellow researcher and colleague Esther Lederberg) thought that Crick was unduly optimistic .
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It was clear that some macromolecule such as a protein was likely to be the genetic molecule. However, it was well known that proteins are structural and functional macromolecules, some of which carry out enzymatic reactions of cells. In the 1940s, some evidence had been found pointing to another macromolecule, DNA, the other major component of chromosomes, as a candidate genetic molecule. In the 1944 Avery-MacLeod-McCarty experiment, Oswald Avery and his collaborators showed that a heritable phenotypic difference could be caused in bacteria by providing them with a particular DNA molecule. However, other evidence was interpreted as suggesting that DNA was structurally uninteresting and possibly just a molecular scaffold for the apparently more interesting protein molecules. Crick was in the right place, in the right frame of mind, at the right time (1949), to join Max Perutz’s project at the University of Cambridge, and he began to work on the X-ray crystallography of proteins. X-ray crystallography theoretically offered the opportunity to reveal the molecular structure of large molecules like proteins and DNA, but there were serious technical problems then preventing X-ray crystallography from being applicable to such large molecules.
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1949-1950 Crick taught himself the mathematical theory of X-ray crystallography . During the period of Crick's study of X-ray diffraction, researchers in the Cambridge lab were attempting to determine the most stable helical conformation of amino acid chains in proteins (the alpha helix). Linus Pauling was the first to identify the 3.6 amino acids per helix turn ratio of the alpha helix. Crick was witness to the kinds of errors that his co-workers made in their failed attempts to make a correct molecular model of the alpha helix; these turned out to be important lessons that could be applied, in the future, to the helical structure of DNA. For example, he learned the importance of the structural rigidity that double bonds confer on molecular structures which is relevant both to peptide bonds in proteins and the structure of nucleotides in DNA.
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1951–1953: DNA structure In 1951 and 1952, together with William Cochran and Vladimir Vand , Crick assisted in the development of a mathematical theory of X-ray diffraction by a helical molecule . This theoretical result matched well with X-ray data for proteins that contain sequences of amino acids in the alpha helix conformation . Helical diffraction theory turned out to also be useful for understanding the structure of DNA . Late in 1951, Crick started working with James Watson at Cavendish Laboratory at the University of Cambridge, England. Using "Photo 51" (the X-ray diffraction results of Rosalind Franklin and her graduate student Raymond Gosling of King's College London, given to them by Gosling and Franklin's colleague Wilkins), Watson and Crick together developed a model for a helical structure of DNA, which they published in 1953 . For this and subsequent work they were jointly awarded the Nobel Prize in Physiology or Medicine in 1962 with Wilkins.
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Molecular biology In 1954, at the age of 37, Crick completed his Ph.D. thesis: "X-Ray Diffraction: Polypeptides and Proteins" and received his degree. Crick then worked in the laboratory of David Harker at Brooklyn Polytechnic Institute, where he continued to develop his skills in the analysis of X-ray diffraction data for proteins, working primarily on ribonuclease and the mechanisms of protein synthesis. David Harker, the American X-ray crystallographer, was described as "the John Wayne of crystallography" by Vittorio Luzzati , a crystallographer at the Centre for Molecular Genetics in Gif-sur-Yvette near Paris, who had worked with Rosalind Franklin.[citation needed ] After the discovery of the double helix model of DNA, Crick's interests quickly turned to the biological implications of the structure. In 1953, Watson and Crick published another article in Nature which stated: "it therefore seems likely that the precise sequence of the bases is the code that carries the genetical information ". In 1956, Crick and Watson speculated on the structure of small viruses. They suggested that spherical viruses such as Tomato bushy stunt virus had icosahedral symmetry and were made from 60 identical subunits.
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During the mid-to-late 1950s Crick was very much intellectually engaged in sorting out the mystery of how proteins are synthesized. By 1958, Crick's thinking had matured and he could list in an orderly way all of the key features of the protein synthesis process : genetic information stored in the sequence of DNA molecules a "messenger" RNA molecule to carry the instructions for making one protein to the cytoplasm adaptor molecules ("they might contain nucleotides") to match short sequences of nucleotides in the RNA messenger molecules to specific amino acids ribonucleic-protein complexes that catalyse the assembly of amino acids into proteins according to the messenger RNA . Molecular biology
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The adaptor molecules were eventually shown to be tRNAs and the catalytic "ribonucleic-protein complexes" became known as ribosomes. An important step was later realization (in 1960) that the messenger RNA was not the same as the ribosomal RNA. None of this, however, answered the fundamental theoretical question of the exact nature of the genetic code. In his 1958 article, Crick speculated, as had others, that a triplet of nucleotides could code for an amino acid. Such a code might be "degenerate", with 4×4×4=64 possible triplets of the four nucleotide subunits while there were only 20 amino acids. Some amino acids might have multiple triplet codes. Crick also explored other codes in which, for various reasons, only some of the triplets were used, "magically" producing just the 20 needed combinations. Experimental results were needed; theory alone could not decide the nature of the code. Crick also used the term "central dogma" to summarize an idea that implies that genetic information flow between macromolecules would be essentially one-way: DNA → RNA → Protein Some critics thought that by using the word "dogma", Crick was implying that this was a rule that could not be questioned, but all he really meant was that it was a compelling idea without much solid evidence to support it. In his thinking about the biological processes linking DNA genes to proteins, Crick made explicit the distinction between the materials involved, the energy required, and the information flow. Crick was focused on this third component (information) and it became the organizing principle of what became known as molecular biology. Crick had by this time become a highly influential theoretical molecular biologist. Molecular biology
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Directed panspermia During the 1960s, Crick became concerned with the origins of the genetic code. In 1966, Crick took the place of Leslie Orgel at a meeting where Orgel was to talk about the origin of life. Crick speculated about possible stages by which an initially simple code with a few amino acid types might have evolved into the more complex code used by existing organisms . At that time, everyone thought of proteins as the only kind of enzymes and ribozymes had not yet been found. Many molecular biologists were puzzled by the problem of the origin of a protein replicating system that is as complex as that which exists in organisms currently inhabiting Earth. In the early 1970s, Crick and Orgel further speculated about the possibility that the production of living systems from molecules may have been a very rare event in the universe, but once it had developed it could be spread by intelligent life forms using space travel technology, a process they called "directed panspermia ". In a retrospective article , Crick and Orgel noted that they had been overly pessimistic about the chances of abiogenesis on Earth when they had assumed that some kind of self-replicating protein system was the molecular origin of life .
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Neuroscience and other interests Crick's period at Cambridge was the pinnacle of his long scientific career, but he left Cambridge in 1977 after 30 years, having been offered (and having refused) the Mastership of Gonville & Caius. James Watson claimed at a Cambridge conference marking the 50th anniversary of the discovery of the structure of DNA in 2003: "Now perhaps it's a pretty well kept secret that one of the most uninspiring acts of the University of Cambridge over this past century was to turn down Francis Crick when he applied to be the Professor of Genetics, in 1958. Now there may have been a series of arguments, which led them to reject Francis. It was really saying, don't push us to the frontier ." The apparently "pretty well kept secret" had already been recorded in Soraya De Chadarevian's Designs For Life: Molecular Biology After World War II, published by Cambridge University Press in 2002. His major contribution to molecular biology in Cambridge is well documented in The History of the University of Cambridge: Volume 4 (1870 to 1990), which was published by CUP in 1992 . According to the University of Cambridge's genetics department official website, the electors of the professorship could not reach consensus, prompting the intervention of then University Vice-Chancellor Lord Adrian. Lord Adrian first offered the professorship to a compromise candidate, Guido Pontecorvo , who refused, and is said to have offered it then to Crick, who also refused.
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In 1976, Crick took a sabbatical year at the Salk Institute for Biological Studies in La Jolla, California. Crick had been a nonresident fellow of the Institute since 1960. Crick wrote, "I felt at home in Southern California ." After the sabbatical, Crick left Cambridge in order to continue working at the Salk Institute. He was also a professor at the University of California, San Diego. He taught himself neuroanatomy and studied many other areas of neuroscience research. It took him several years to disengage from molecular biology because exciting discoveries continued to be made, including the discovery of alternative splicing and the discovery of restriction enzymes, which helped make possible genetic engineering. Eventually, in the 1980s, Crick was able to devote his full attention to his other interest, consciousness. His autobiographical book, What Mad Pursuit: A Personal View of Scientific Discovery, includes a description of why he left molecular biology and switched to neuroscience . Upon taking up work in theoretical neuroscience, Crick was struck by several things : there were many isolated subdisciplines within neuroscience with little contact between them many people who were interested in behaviour treated the brain as a black box consciousness was viewed as a taboo subject by many neurobiologists Neuroscience and other interests
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Crick hoped he might aid progress in neuroscience by promoting constructive interactions between specialists from the many different subdisciplines concerned with consciousness. He even collaborated with neurophilosophers such as Patricia Churchland . In 1983, as a result of their studies of computer models of neural networks, Crick and Mitchison proposed that the function of REM sleep is to remove certain modes of interactions in networks of cells in the mammalian cerebral cortex; they called this hypothetical process 'reverse learning' or 'unlearning'. In the final phase of his career, Crick established a collaboration with Christof Koch that lead to publication of a series of articles on consciousness during the period spanning from 1990 to 2005. Crick made the strategic decision to focus his theoretical investigation of consciousness on how the brain generates visual awareness within a few hundred milliseconds of viewing a scene. Crick and Koch proposed that consciousness seems so mysterious because it involves very short-term memory processes that are as yet poorly understood. Crick also published a book describing how neurobiology had reached a mature enough stage so that consciousness could be the subject of a unified effort to study it at the molecular, cellular and behavioural levels. Crick's book The Astonishing Hypothesis made the argument that neuroscience now had the tools required to begin a scientific study of how brains produce conscious experiences. Crick was skeptical about the value of computational models of mental function that are not based on details about brain structure and function. Neuroscience and other interests
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Death Crick died of colon cancer on the morning of 28 July 2004 at the University of California, San Diego (UCSD) Thornton Hospital in La Jolla; he was cremated and his ashes were scattered into the Pacific Ocean. A public memorial was held on 27 September 2004 at the Salk Institute, La Jolla, near San Diego, California; guest speakers included James Watson, Sydney Brenner, Alex Rich, Seymour Benzer , Aaron Klug, Christof Koch, Pat Churchland , Vilayanur Ramachandran, Tomaso Poggio , Leslie Orgel , Terry Sejnowski , his son Michael Crick, and his youngest daughter Jacqueline Nichols . A private memorial for family and colleagues was held on 3 August 2004.
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