Crick Francis discovery of the structure of DNA. James Dewey Watson, Francis Crick

The DNA double helix is ​​50 years old!

On Saturday, February 28, 1953, two young scientists, J. Watson and F. Crick, in a small diner Eagle in Cambridge they announced to a crowd of people who came to lunch that they had discovered the secret of life. Many years later, Odile, the wife of F. Crick, said that, of course, she did not believe him: when he came home, he often said something like that, but then it turned out that this was a mistake. This time there was no mistake, and with this statement, a revolution in biology began that continues to this day.

April 25, 1953 in the magazine Nature three articles on the structure of nucleic acids appeared at once. In one of them, written by J. Watson and F. Crick, the structure of the DNA molecule in the form of a double helix was proposed. In two others, written by M. Wilkins, A. Stokes, G. Wilson, R. Franklin and R. Gosling, experimental data were presented confirming the helical structure of DNA molecules. The story of the discovery of the DNA double helix resembles an adventure novel and deserves at least a brief summary.

The most important ideas about the chemical nature of genes and the matrix principle of their reproduction were first clearly formulated in 1927 by N.K. Koltsov (1872–1940). His student N.V. Timofeev-Resovsky (1900–1981) took these ideas and developed them as the principle of convariant reduplication of genetic material. German physicist Max Delbrück (1906–1981; Nobel Prize 1969), active in the mid-1930s At the Kaiser Wilhelm Institute of Chemistry in Berlin, under the influence of Timofeev-Ressovsky, he became so interested in biology that he abandoned physics and became a biologist.

For a long time, in full accordance with the definition of life given by Engels, biologists believed that some special proteins were the hereditary substance. No one thought that nucleic acids could have anything to do with genes - they seemed too simple. This continued until 1944, when a discovery was made that radically changed the entire further development of biology.

This year, Oswald Avery, Colin McLeod and McLean McCarthy published an article stating that in pneumococci, inherited properties are transferred from one bacteria to another using pure DNA, i.e. DNA is the substance of heredity. McCarthy and Avery then showed that treating DNA with a DNA-cleaving enzyme (DNase) causes it to lose the properties of the gene. It is still not clear why this discovery was not awarded the Nobel Prize.

Shortly before that, in 1940, L. Pauling (1901–1994; Nobel Prizes in 1954 and 1962) and M. Delbrück developed the concept of molecular complementarity in antigen-antibody reactions. In the same years, Pauling and R. Corey showed that polypeptide chains can form helical structures, and somewhat later, in 1951, Pauling developed a theory that made it possible to predict the types of X-ray patterns for various helical structures.

After the discovery of Avery et al., despite the fact that it did not convince the supporters of the theory of protein genes, it became clear that it was necessary to determine the structure of DNA. Among those who understood the importance of DNA for biology, a race for results began, accompanied by fierce competition.

X-ray machine used in the 1940s to study the crystal structure of amino acids and peptides

In 1947–1950 E. Chargaff, on the basis of numerous experiments, established the rule of correspondence between nucleotides in DNA: the numbers of purine and pyrimidine bases are the same, and the number of adenine bases is equal to the number of thymine bases, and the number of guanine bases is equal to the number of cytosine bases.

The first structural works (S.Ferberg, 1949, 1952) showed that DNA has a helical structure. Having vast experience in determining the structure of proteins from x-rays, Pauling would no doubt have been able to quickly solve the problem of the structure of DNA, if he had any decent x-rays. However, there were none, and according to what he managed to get, he could not make an unambiguous choice in favor of one of the possible structures. As a result, in his haste to publish the result, Pauling chose the wrong option: in a paper published in early 1953, he proposed a structure in the form of a three-stranded helix, in which phosphate residues form a rigid core, and nitrogenous bases are located on the periphery.

Many years later, recalling the story of the discovery of the structure of DNA, Watson remarked that “Linus [Pauling] did not deserve to guess the right solution. He didn't read the articles and didn't talk to anyone. Moreover, he even forgot his own article with Delbrück, which talks about the complementarity of gene replication. He thought he could figure out the structure just because he was so smart.”

When Watson and Crick began work on the structure of DNA, much was already known. It remained to obtain reliable X-ray structural data and interpret them on the basis of the information already available at that time. How it all happened is well described in the famous book by J. Watson "Double Helix", although many of the facts in it are presented in a very subjective way.

J. Watson and F. Crick on the verge of a great discovery

Of course, in order to build a double helix model, extensive knowledge and intuition were needed. But if there were no coincidence of several accidents, the model could appear several months later, and other scientists could be its authors. Here are some examples.

Rosalind Franklin (1920–1958), who worked with M. Wilkins (Nobel Prize in 1962) at King's College (London), obtained the highest quality DNA X-rays. But this work was of little interest to her, she considered it routine and was in no hurry to draw conclusions. This was facilitated by her bad relationship with Wilkins.

At the very beginning of 1953, Wilkins, without the knowledge of R. Franklin, showed Watson her radiographs. In addition, in February of the same year, Max Perutz showed Watson and Crick the annual report of the Medical Research Council with a review of the work of all leading employees, including R. Franklin. This was enough for F. Crick and J. Watson to understand how the DNA molecule should be arranged.

X-ray of DNA obtained by R. Franklin

In an article by Wilkins et al., published in the same issue Nature, as the article by Watson and Crick, it is shown that, judging by the X-ray patterns, the structure of DNA from different sources is approximately the same and is a helix in which the nitrogenous bases are located inside, and the phosphate residues are outside.

The article by R. Franklin (with her student R. Gosling) was written in February 1953. Already in the initial version of the article, she described the structure of DNA in the form of two coaxial and shifted relative to each other along the axis spirals with nitrogenous bases inside and phosphates outside. According to her, the pitch of the DNA helix in form B (ie, at a relative humidity of >70%) was 3.4 nm, and there were 10 nucleotides per turn. Unlike Watson and Crick, Franklin did not build models. For her, DNA was no more interesting to study than coal and carbon, which she worked on in France before coming to King's College.

When she learned about the Watson-Crick model, she added by hand in the final version of the article: “Thus, our general ideas do not contradict the Watson and Crick model given in the previous article.” Which is not surprising, because. this model was based on her experimental data. But neither Watson nor Crick, in spite of the most friendly relations with R. Franklin, they never told her what, years after her death, they repeated publicly many times - that without her data they would never have been able to build their model.

R. Franklin (far left) at a meeting with colleagues in Paris

R. Franklin died of cancer in 1958. Many believe that if she lived to 1962, Nobel Committee I would have to break my strict rules and give the award to not three, but four scientists. In recognition of her and Wilkins' accomplishments, one of the buildings at King's College was named "Franklin-Wilkins," forever connecting the names of people who barely spoke to each other.

Upon acquaintance with the article by Watson and Crick (it is given below), one is surprised by its small volume and lapidary style. The authors perfectly understood the significance of their discovery and, nevertheless, limited themselves to a description of the model and a brief indication that “from the postulated ... specific pairing, a possible mechanism for copying genetic material immediately follows.” The model itself was taken as if “from the ceiling” - there is no indication of how it was received. Its structural characteristics are not given, except for the pitch and the number of nucleotides per helix pitch. The formation of pairs is also not clearly described, because at that time two systems of numbering of atoms in pyrimidines were used. The article is illustrated with only one drawing made by F. Crick's wife. However, for ordinary biologists, the crystallographically overloaded papers by Wilkins and Franklin were difficult to read, while Watson and Crick's paper was understood by everyone.

Later, both Watson and Crick admitted that they were simply afraid to state all the details in the first article. This was done in a second article entitled "Genetic Implications from the Structure of DNA" and published in Nature May 30 of the same year. It provides justifications for the model, all the dimensions and details of the DNA structure, circuits of chain formation and base pairing, and discusses the various implications for genetics. The nature and tone of the presentation indicate that the authors are quite confident in their correctness and the importance of their discovery. True, they connected the G–C pair with only two hydrogen bonds, but already a year later they indicated in a methodological article that three bonds were possible. Pauling soon confirmed this with calculations.

Watson and Crick's discovery showed that genetic information is written in DNA in a four-letter alphabet. But it took another 20 years to learn how to read it. The question immediately arose as to what genetic code. The answer to it was proposed in 1954 by the theoretical physicist G.A. Gamow *: information in DNA is encoded by triplets of nucleotides - codons. This was confirmed experimentally in 1961 by F. Crick and S. Brenner. Then, within 3–4 years, in the works of M. Nirenberg (Nobel Prize 1965), S. Ochoa (Nobel Prize 1959), H. Korana (Nobel Prize 1965) and others, the correspondence between codons and amino acids.

In the mid 1970s. F. Sanger (b. 1918; Nobel Prizes in 1958 and 1980), who also worked at Cambridge, developed a method for determining nucleotide sequences in DNA. Sanger used it to sequence the 5386 bases that make up the bacteriophage jX174 genome. However, the genome of this phage is a rare exception: it is a single-stranded DNA.
The real era of genomes began in May 1995, when J.K. Venter announced the decoding of the first genome unicellular organism– bacteria haemophilus influenzae. The genomes of about 100 different organisms have now been deciphered.

Until recently, scientists thought that everything in a cell is determined by the sequence of bases in DNA, but life, apparently, is much more complicated.
It is now well known that DNA often has a shape other than the Watson-Crick double helix. More than 20 years ago, the so-called Z-helix structure of DNA was discovered in laboratory experiments. This is also a double helix, but twisted in the opposite direction compared to the classical structure. Until recently, it was believed that Z-DNA is not related to living organisms, but recently a group of researchers from the National Institutes of Heart, Lung and Blood (USA) found that one of the genes of the immune system is activated only when part of its regulatory sequence passes into Z-shape. Now it is assumed that the temporary formation of the Z-form may be a necessary link in the regulation of the expression of many genes. In some cases, viral proteins have been found to bind to Z-DNA and cause cell damage.

In addition to helical structures, DNA can form the well-known twisted rings in prokaryotes and some viruses.

Last year, S. Nidle from the Institute for Cancer Research (London) discovered that the irregular ends of chromosomes - telomeres, which are single strands of DNA - can fold into very regular structures resembling a propeller). Similar structures were found in other parts of the chromosomes and were called G-quadruplexes, since they are formed by DNA regions rich in guanine.

Apparently, such structures contribute to the stabilization of the DNA segments on which they are formed. One of the G-quadruplexes was found directly next to the gene c-MYC, the activation of which causes cancer. In this case, it can prevent gene activator proteins from binding to DNA, and researchers have already started looking for drugs that stabilize the structure of G-quadruplexes, in the hope that they will help in the fight against cancer.

IN last years not only the ability of DNA molecules to form structures other than the classical double helix was discovered. To the surprise of scientists, in the nucleus of a cell, DNA molecules are in continuous motion, as if “dancing”.

It has long been known that DNA forms complexes with histone proteins in the nucleus with protamine in spermatozoa. However, these complexes were considered durable and static. With the help of modern video technology, it was possible to capture the dynamics of these complexes in real time. It turned out that DNA molecules constantly form fleeting bonds with each other and with a variety of proteins that, like flies, hover around DNA. Some proteins move so fast that they travel from one side of the nucleus to the other in 5 seconds. Even histone H1, which is most strongly associated with the DNA molecule, dissociates every minute and binds to it again. This variability of connections helps the cell to regulate the activity of its genes - DNA constantly checks for the presence of transcription factors and other regulatory proteins in its environment.

The nucleus, which was considered a rather static formation - a repository of genetic information - actually lives a stormy life, and the well-being of the cell largely depends on the choreography of its components. Some human diseases can be caused by imbalances in the coordination of these molecular dances.

Obviously, with such an organization of the life of the nucleus, its different parts are not equivalent - the most active "dancers" should be closer to the center, and the least active - to the walls. And so it turned out. For example, in humans, chromosome 18, which has only a few active genes, is always located near the border of the nucleus, and chromosome 19, full of active genes, is always near its center. Moreover, the movement of chromatin and chromosomes, and even just mutual arrangement chromosomes, apparently, affects the activity of their genes. Thus, the proximity of chromosomes 12, 14 and 15 in the nuclei of mouse lymphoma cells is considered a factor contributing to the transformation of the cell into cancer.

The past half century in biology has become the era of DNA - in the 1960s. deciphered the genetic code, in the 1970s. recombinant DNA was obtained and sequencing methods were developed, in the 1980s. polymerase chain reaction (PCR) was developed; in 1990, the Human Genome Project was launched. One of Watson's friends and colleagues, W. Gilbert, believes that traditional molecular biology is dead - now everything can be found out by studying genomes.

F. Crick among the laboratory staff molecular biology in Cambridge

Now, looking at Watson and Crick's papers 50 years ago, one is surprised how many of the assumptions turned out to be true or close to the truth - after all, they had almost no experimental data. As for the authors themselves, both scientists are celebrating the fiftieth anniversary of the discovery of the structure of DNA, now actively working in different fields of biology. J. Watson was one of the initiators of the "Human Genome" project and continues to work in the field of molecular biology, and in early 2003 F. Crick published an article on the nature of consciousness.

J.D. watson,
F.G.K. scream,
Department for the Study of the Molecular Structure of Biological Systems of the Medical Research Council, Cavendish Laboratory, Cambridge. April 25, 1953

Molecular structure of nucleic acids

We want to propose a model for the structure of a salt of deoxyribonucleic acid (DNA). This structure has new properties of interest to biology.
The structure of the nucleic acid has already been proposed by Pauling and Corey. They kindly allowed us to review the manuscript of their article prior to publication. Their model consists of three intertwined chains with phosphates located near the axis of the helix and nitrogenous bases at the periphery. In our opinion, such a structure is unsatisfactory for two reasons. First, we believe that the material under study, which gives X-ray reflections, is a salt, and not a free acid. Without acidic hydrogen atoms, it is not clear what forces can maintain the integrity of such a structure, especially given that the negatively charged phosphate groups near its axis will repel each other. Secondly, some of the van der Waals distances turn out to be too small.
Another three-strand structure has been proposed by Fraser (in press). In his model, phosphates are outside, and nitrogenous bases, interconnected by hydrogen bonds, are inside the helix. In the article, this structure is defined very poorly, and for this reason we will not comment on it.
We want to propose a radically different structure of the salt of deoxyribonucleic acid. This structure consists of two helical chains twisted around a common axis. We proceeded from the usual assumptions, namely that each chain is formed by b-D-deoxyribofuranose residues connected by 3,5" bonds. These chains (but not their bases) are connected by bonds (dyads) perpendicular to the helix axis. Both chains form a right helix, but, thanks to the dyads, they have opposite directions. Each chain slightly resembles Ferberg's Model #1 in that the bases are on the inside of the helix and the phosphates are on the outside. The configuration of the sugar and the atoms near it is close to Ferberg's "standard configuration", in which the sugar is approximately perpendicular to its associated base. The residues on each circuit are arranged in 3.4 A steps in the direction z. We assumed that the angle between neighboring residues is 36°, so that this structure is repeated every 10 residues, i.e. through 34 A. The distance from the axis to the phosphorus atom is 10 A. Since the phosphates are located outside, they are easily accessible to cations.
The whole structure is open and contains quite a lot of water. As the water content decreases, the bases can be expected to tilt somewhat and the whole structure to become more compact.
A novel feature of the structure is the way the chains are held together by purine and pyrimidine bases. The planes of the bases are perpendicular to the axis of the helix. They are paired with each other, with one base on the first chain being hydrogen bonded to one base on the second chain in such a way that these bases are located side by side with each other and have the same z-coordinate. In order for a bond to form, one base must be purine and the other pyrimidine. Hydrogen bonds are formed between position 1 of the purine and position 1 of the pyrimidine and between position 6 of the purine and position 6 of the pyrimidine.
It is assumed that the bases are included in this structure only in the most probable tautomeric form (i.e., in the keto and not in the enol form). It has been found that only specific base pairs can form bonds with each other. These pairs are: adenine (purine) - thymine (pyrimidine) and guanine (purine) - cytosine (pyrimidine).
In other words, if adenine is one member of a pair on any chain, then, according to this assumption, the other member of the pair must be thymine. The same applies to guanine and cytosine. The sequence of bases on one strand appears to be unlimited. However, since only certain base pairs can form, given the base sequence of one strand, the base sequence of the other strand is determined automatically.
It has been experimentally found that in DNA the ratio of the number of adenines to the number of thymines and the number of guanines to the number of cytosines is always close to unity.
It is probably not possible to construct such a structure with ribose instead of deoxyribose, since the extra oxygen atom makes the van der Waals distance too small.
The X-ray diffraction data on deoxyribonucleic acid published so far are insufficient for a rigorous verification of our model. As far as we can judge, it approximates the experimental data, but it cannot be considered proven until it is compared with more accurate experimental data. Some of them are shown in the following article. We were not aware of the details of the results presented therein when we came up with our structure, which is based mainly, though not exclusively, on published experimental data and stereochemical considerations.
It should be noted that a possible mechanism for copying genetic material immediately follows from the specific pairing that we postulated.
All details of the structure, including the conditions necessary for its construction, and the sets of atomic coordinates will be given in subsequent publications.
We are very grateful to Dr. Jerry Donahue for his constant advice and criticism, especially regarding interatomic distances. We were also encouraged general idea about unpublished experimental data and ideas of Dr. M.G.F. Wilkins and Dr. R.E. Franklin and their staff at King's College London. One of us (J.D.W.) received a scholarship from the National Infantile Palsy Foundation.

* Georgy Antonovich Gamov (1904–1968, emigrated to the USA in 1933) is one of the greatest scientists of the 20th century. He is the author of the theory of theta decay and the tunnel effect in quantum mechanics; liquid-drop model of the atomic nucleus - the basis of the theories of nuclear decay and thermonuclear reactions; theory of the internal structure of stars, which showed that the source of solar energy are thermonuclear reactions; theories " big bang» in the evolution of the Universe; theory of relic radiation in cosmology. His non-fiction books are well known, such as the series of books about Mr. Tompkins ("Mr. Tompkins in Wonderland", "Mr. Tompkins inside himself", etc.), "One, two, three ... infinity", "A planet called Earth " and etc.

Quotes: 1. Process scientific research deeply intimate: sometimes we ourselves do not know what we are doing. 2. An honest person, armed with all the knowledge at our disposal, can only state that in a certain sense the origin of life at the moment seems almost like a miracle ... 3. ... Protein is like a paragraph written in a language with a twenty-letter alphabet, the specific nature of the protein in this case, it is determined by a specific order of letters. With one trivial exception, this font never changes. Animals, plants, microorganisms and viruses all use the same set of letters... of four letters, into the language of the squirrel, the executive language, consisting of twenty letters. 5. We assumed that microorganisms should have traveled in the head of the drone to avoid spoilage. spaceship, sent to Earth by a highly developed civilization that originated somewhere else several billion years ago ... Life originated here when these organisms fell into the primordial ocean and began to multiply.

Achievements and contributions:

Professional, social position: Francis Crick is an English molecular biologist, physicist and neuroscientist.
Main contribution (what is known): Francis Crick is best known for his research leading to the discovery of the structure of DNA in 1952, and for his theories of consciousness and the origin of life.
Contributions: He is best known as one of the two co-discoverers, along with James Watson, of the double helix structure of the DNA molecule in 1953. He also played an important role in research relating to the discovery of the genetic code.
In Cambridge, he met an American named James Watson and, together with his colleague Maurice Wilkinson, they tried to figure out the structure of deoxyribonucleic acid (DNA).
Their research was based on Crick's theory, Watson's theory of the phage, X-ray studies by Maurice Wilkins and Rosalind Franklin, and the discovery of Erwin Chargaff (1950), stating that DNA contains equal amounts of the four nitrogenous bases - adenine, thymine, guanine, and cytosine.
In 1953, based on these various scientific theories the structure of DNA was revealed, structured like two twisted, spiral staircases: later known as double helix model.
Crick and Watson first published one of their four papers reporting their discovery on April 25, 1953 in the journal Nature.
In 1962, Francis Crick, James D. Watson, and Maurice Wilkins were jointly awarded the Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and their importance for the transmission of information in living organisms."
After the discovery of the double helix, Crick began to work on the relationship between DNA and the genetic code. He revealed the nature of the genetic code. So the code determines the correspondence between three-nucleotide sequences called codons and amino acids. Three nitrogenous bases (triplet) code for one amino acid. In doing so, he revealed the mechanism of protein synthesis. The original DNA molecule separates like a zipper. Each half of the DNA molecule serves as a template, a template for building new complementary double helixes.
In this case, each nitrogenous base adenine (A), thymine (T), guanine (G) and cytosine (C) pairs with its strictly defined complementary base.
Crick is widely credited for coining the term "central dogma" to summarize the idea that the transfer of genetic information in cells occurs through a one-way flow from DNA, through RNA, to protein.
Later, two major unsolved problems in biology became the subject of Crick's scientific interest. The first concerned the question of how molecules are transformed from inanimate to living, and the second, how the brain affects the work of consciousness. In his work Life as It Is: Its Origin and Nature (1981), Crick suggested that life on Earth could have originated from microorganisms that were introduced from another planet.
He and his colleague L. Orgel called this theory “direct panspermia”.
His theories of consciousness and the origin of life have had a significant impact on all scientists working in this field.
Honorary titles, awards: Nobel Prize in Physiology or Medicine (1962), Gairdner International Prize (1962), Royal Medal (1972), Copley Medal (1975) Albert Medal (Royal Society of Arts) (1987), Order of Merit (1991).
Main works:"The structure of the substance of heredity" (1953), "On molecules and man" (1966), "Life as it is: its origin and nature" (1981), "Surprising hypotheses: the scientific search for the soul" (1994).

Career and personal life:

Origin: He was born and raised in Weston Favell, a small village not far from English city Northampton, in which his Crick father Harry Creek (1887-1948) and his uncle established the family shoe factory. His mother was Annie Elizabeth Creek (maiden name Wilkins) (1879-1955).
Education: He was educated in high school Northampton, and after 14 years at Mill Hill School in London. He received a bachelor's degree in physics from University College London (UCL), a PhD from the University of Cambridge, and a postdoctoral fellow from the Polytechnic Institute of Brooklyn.
Influenced: Erwin Schrödinger
The main stages of professional activity: In 1937, at the age of 21, Crick received his bachelor's degree in physics from University College London (UCL).
His work and further studies at the university were interrupted by participation in the Second World War. From 1940 to 1947 he served as a scientist in the Navy Department, where he designed naval mines.
After serving in the army, in 1947 Crick became a graduate student and Fellow of Guy's College and worked at the Cambridge Medical Laboratory on the use of X-ray diffraction to determine the spatial structure of large biological molecules. At this time, Crick, influenced by the ideas of Erwin Schrödinger, outlined in his book What is Life? (1944), switched his interest from physics to biology.
In 1949, Francis Crick moved to the famous Cavendish Laboratory in Cambridge, where he began to study the molecular structure of proteins.
Francis Crick was 35 years old when he and his colleague James Watson began working on unraveling the structure of DNA, the genetic code of life.
After 1976, he worked at the Salk Institute in San Diego, where he served as president from 1994 to 1995. At the Institute, in collaboration with Christoph Koch, he studied the neural correlates of conscious visual experience, trying to understand how neural patterns correspond to conscious visual experience.
The main stages of personal life: From a very young age, Francis was fascinated by science and the knowledge gained from reading books. He was educated at Northampton Grammar School and, after the age of 14, at Mill Hill School, London (on a scholarship), where he studied mathematics, physics and chemistry with his best friend John Shilston.
Crick first married in 1940 to Ruth Doreen Dodd (1913-2011). They had a son, Michael Francis Compton Creek (b. November 25, 1940). He divorced his wife in 1947. Later in 1949 he married Odile Speed ​​(1920 - 2007. They had two daughters, Gabrielle Ann (b. July 15, 1951) and Jacqueline Marie-Thérèse (later Nichols) (March 12, 1954 - February 28, 2011). They remained together until Crick's death in 2004.
He was cremated and his ashes were scattered over the Pacific Ocean.
Zest: Francis Crick's grandfather was a shoemaker and an amateur scientist. His uncle Walter was also fond of science and in his younger years Francis did some chemical experiments with him. The first model of the spatial structure of the DNA molecule was constructed from balls, pieces of wire and cardboard.

English molecular biologist Francis Harry Compton Crick was born in Northampton, the eldest of two sons of Harry Compton Crick, a wealthy shoe manufacturer, and Anna Elizabeth (Wilkins) Crick. Having spent his childhood in Northampton, he attended high school classical school. During the economic crisis that followed the First World War, the family's commercial affairs fell into disrepair, and K.'s parents moved to London. As a student at Mill Hill School, K. showed big interest to physics, chemistry and mathematics. In 1934 he entered University College London to study physics and graduated three years later with a Bachelor of Science degree. Completing education at University College, K. considered the viscosity of water at high temperatures; this work was interrupted in 1939 by the outbreak of World War II.

During the war years, K. engaged in the creation of mines in the research laboratory of the Naval Ministry of Great Britain. For two years after the end of the war, he continued to work in this ministry and it was then that he read Erwin Schrödinger's famous book What is Life? Physical Aspects of the Living Cell” (“What Is Life? The Physical Aspects of the Living Cell”), published in 1944. In the book, Schrodinger asks the question: “How can spatio-temporal events occurring in a living organism be explained from the position physics and chemistry?

The ideas presented in the book, so influenced K. that he, intending to do particle physics, switched to biology. With the support of Archibald W. Hill K. received a scholarship from the Council for Medical Research and in 1947. began working at the Strangeway Laboratory in Cambridge. Here he studied biology, organic chemistry, and X-ray diffraction techniques used to determine the spatial structure of molecules. His knowledge of biology expanded significantly after moving in 1949 to the Cavendish Laboratory in Cambridge, one of the world's centers of molecular biology.

Under the leadership of Max Perutz K. investigated the molecular structure of proteins, in connection with which he had an interest in the genetic code of the amino acid sequence in protein molecules. About 20 essential amino acids serve as monomeric units from which all proteins are built. Studying the issue, defined by him as "the boundary between living and non-living", K. tried to find the chemical basis of genetics, which, he suggested, could be embedded in deoxyribonucleic acid (DNA).

Genetics as a science arose in 1866 when Gregor Mendel formulated the position that "elements", later called genes, determine inheritance physical properties. Three years later, the Swiss biochemist Friedrich Miescher discovered nucleic acid and showed that it is contained in the cell nucleus. At the dawn of a new century, scientists discovered that genes are located on chromosomes, structural elements cell nuclei. In the first half of the XX century. biochemists determined the chemical nature of nucleic acids, and in the 40s. researchers have found that genes are formed from one of these acids, DNA. It has been proven that genes, or DNA, direct the biosynthesis (or formation) of cellular proteins called enzymes and thus control the biochemical processes in the cell.

When K. began working on his doctoral dissertation at Cambridge, it was already known that nucleic acids consist of DNA and RNA (ribonucleic acid), each of which is formed by molecules of the monosaccharide group of pentoses (deoxyribose or ribose), phosphate and four nitrogenous bases - adenine, thymine, guanine and cytosine (RNA contains uracil instead of thymine). In 1950, Erwin Chargaff of Columbia University showed that DNA contains equal amounts of these nitrogenous bases. Maurice H.F. Wilkins and his colleague Rosalind Franklin of King's College London conducted X-ray diffraction studies of DNA molecules and concluded that DNA has the shape of a double helix, resembling a spiral staircase.

In 1951, the twenty-three-year-old American biologist James D. Watson invited K. to work at the Cavendish Laboratory. Subsequently, they established close creative contacts. Based on the early studies of Chargaff, Wilkins and Franklin, K. and Watson set out to determine chemical structure DNA. Within two years, they developed the spatial structure of the DNA molecule by constructing its model from balls, pieces of wire and cardboard. According to their model, DNA is a double helix consisting of two chains of monosaccharide and phosphate (deoxyribose phosphate) connected by base pairs within the helix, with adenine connected to thymine, and guanine to cytosine, and the bases to each other by hydrogen bonds.

The model allowed other researchers to visualize DNA replication clearly. The two chains of the molecule are separated at hydrogen bonds, like opening a zipper, after which a new one is synthesized on each half of the old DNA molecule. The base sequence acts as a template, or blueprint, for the new molecule.

In 1953, Mr.. K. and Watson completed the creation of a DNA model. In the same year, K. received his Ph.D. from Cambridge, defending his thesis on X-ray diffraction analysis of protein structure. During next year he studied protein structure at Brooklyn polytechnic institute in New York and lectured at various US universities. Returning to Cambridge in 1954, he continued his research at the Cavendish Laboratory, concentrating on deciphering the genetic code. Originally a theoretician, K. began with Sydney Brenner to study genetic mutations in bacteriophages (viruses that infect bacterial cells).

By 1961, three types of RNA were discovered: messenger, ribosomal, and transport. K. and his colleagues proposed a way to read the genetic code. According to K.'s theory, messenger RNA receives genetic information from DNA in the cell nucleus and transfers it to ribosomes (sites of protein synthesis) in the cytoplasm of the cell. Transfer RNA carries amino acids into ribosomes.

Informational and ribosomal RNA, interacting with each other, provide a combination of amino acids to form protein molecules into correct sequence. The genetic code is made up of triplets of nitrogenous bases of DNA and RNA for each of the 20 amino acids. Genes consist of numerous basic triplets, which K. called codons; codons are the same in different species.

K., Wilkins and Watson divided Nobel Prize in Physiology or Medicine 1962 "for their discoveries concerning the molecular structure of nucleic acids and their significance for the transmission of information in living systems." A.V. Engström of the Karolinska Institute said at the awards ceremony: "The discovery of the spatial molecular structure ... DNA is extremely important, because it outlines the possibilities for understanding in great detail the general and individual characteristics of all living things." Engstrom noted that "the deciphering of the double helix structure of deoxyribonucleic acid with a specific pairing of nitrogenous bases opens up fantastic opportunities for unraveling the details of the control and transmission of genetic information."

In the year of receiving the Nobel Prize K. became head of the biological laboratory at the University of Cambridge and a foreign member of the Council of the Salk Institute in San Diego (California). In 1977, he moved to San Diego, having received an invitation to become a professor. At the Salkovsky Institute K. conducted research in the field of neurobiology, in particular studied the mechanisms of vision and dreams. In 1983, with the English mathematician Graham Mitchison, he proposed that dreams are a side effect of the process by which the human brain is freed from excessive or useless associations accumulated during wakefulness. Scientists have hypothesized that this form of "reverse learning" exists to prevent neural overload.

In the book "Life as it is: its origin and nature" ("Life Itself: Its Origin and Nature", 1981) K. noted the amazing similarity of all forms of life. "With the exception of mitochondria," he wrote, "the genetic code is identical in all living objects currently studied." Referring to discoveries in molecular biology, paleontology and cosmology, he suggested that life on Earth could have originated from microorganisms that were scattered throughout space from another planet; this theory he and his colleague Leslie Orgel called "immediate panspermia".

In 1940, Mr.. K. married Ruth Doreen Dodd; they had a son. They divorced in 1947, and two years later K. married Odile Speed. They had two daughters.

Numerous awards to. include the Charles Leopold Mayer Prize of the French Academy of Sciences (1961), the American Research Society Scientific Prize (1962), the Royal Medal (1972), the Royal Society Copley Medal (1976). K. - Honorary Member of the Royal Society of London, the Royal Society of Edinburgh, the Royal Irish Academy, the American Association for the Advancement of Sciences, the American Academy of Arts and Sciences and the US National Academy of Sciences.

James Watson is a pioneer in molecular biology who, along with Francis Crick and Maurice Wilkins, is credited with discovering the DNA double helix. In 1962, they received the Nobel Prize in Medicine for their work.

James Watson: biography

Born in Chicago, USA on April 6, 1928. He attended Horace Mann School and then South Shore High School. At the age of 15, he entered the University of Chicago under an experimental scholarship program for gifted children. Interest in bird life led James Watson to study biology, and in 1947 he was awarded a Bachelor of Science degree in zoology. After reading Erwin Schrödinger's landmark book What is Life? he switched to genetics.

After being rejected by Caltech and Harvard, James Watson won a scholarship to graduate school at Indiana University. In 1950 for his work on the impact x-ray radiation for the reproduction of bacteriophage viruses, he was awarded a doctorate in zoology. From Indiana, Watson moved to Copenhagen and continued his study of viruses as a member of the National Research Council.

Unravel the DNA!

After visiting the New York laboratory at Cold Spring Harbor, where he got acquainted with the results of the research of Hershey and Chase, Watson became convinced that DNA is the molecule responsible for the transmission of genetic information. He was fascinated by the idea that if you understand its structure, you can determine how data is transmitted between cells. Virus research no longer interested him as much as this new direction.

In the spring of 1951, at a conference in Naples, he met Maurice Wilkins. The latter demonstrated the results of the first attempts to use X-ray diffraction to image the DNA molecule. Watson, excited by Wilkins' findings, arrived in Britain in the fall. He got a job at the Cavendish Laboratory, where he began to collaborate with Francis Crick.

First attempts

In an attempt to unravel the molecular structure of DNA, James Watson and Francis Crick decided to use a model-building approach. Both were convinced that unraveling its structure would play a key role in understanding the transfer of genetic information from parent to daughter cells. Biologists realized that the discovery of the structure of DNA would be a major scientific breakthrough. At the same time, they were aware of the existence of competitors among other scientists, such as Linus Pauling.

Crick and James Watson modeled DNA with great difficulty. None of them had chemical education so they used standard chemistry textbooks to cut out cardboard configurations chemical bonds. A visiting graduate student noted that, according to new data missing from the books, one of his cardboard chemical bonds was used in reverse. Around the same time, Watson attended a lecture by Rosalind Franklin at nearby King's College. Apparently he didn't listen very carefully.

Unforgivable mistake

As a result of the error, scientists' first attempt to build a DNA model failed. James Watson and Francis Crick built a triple helix with nitrogen bases on the outside of the structure. When they presented the model to colleagues, Rosalind Franklin subjected her to harsh criticism. The results of her research clearly proved the existence of two forms of DNA. The wetter one matched the one that Watson and Crick were trying to build, but they created a model of DNA without water present in it. Franklin noted that if her work were correctly interpreted, then the nitrogen bases would be located inside the molecule. Embarrassed by such a public failure, the director of the Cavendish Laboratory recommended that the researchers abandon their approach. Scientists officially took other directions, but in private they continued to think about the problem of DNA.

Peeped discovery

Wilkins, who worked at King's College with Franklin, was in personal conflict with her. Rosalind was so unhappy that she decided to move her research elsewhere. It is not clear how, but Wilkins got at his disposal one of her best x-rays DNA molecules. She may even have given it to him herself when she was cleaning out her office. But it is certain that he took the image out of the lab without Franklin's permission and showed it to his friend Watson in the Cavendish. Subsequently, in his book The Double Helix, he wrote that at the moment when he saw the picture, his jaw dropped and his pulse quickened. Everything was incredibly simpler than the previously obtained A-form. Also, the black cross of reflections that dominated the photo could only have come from the spiral structure.

Nobel Prize Laureate

The biologists used the new data to create a double-stranded helix model with nitrogenous bases in pairs A-T and C-G in the center. This pairing immediately suggested to Crick that one side of the molecule could serve as a template for the exact repetition of DNA sequences for the transmission of genetic information during cell division. This second, successful model was presented in February 1951. In April 1953 they published their findings in the journal Nature. The article caused a sensation. Watson and Crick established that DNA has the form of a double helix, or "spiral staircase". Two chains in it were disconnected, like a "lightning", and reproduced the missing parts. Thus, each deoxyribonucleic acid molecule is able to create two identical copies.

The abbreviation DNA and the elegant double helix model have become known throughout the world. Watson and Crick also became famous. Their discovery revolutionized the study of biology and genetics, making possible the genetic engineering methods used in modern biotechnology.

An article in Nature led to them and Wilkins being awarded the Nobel Prize in 1962. The rules of the Swedish Academy allow no more than three scientists to be awarded. Rosalind Franklin died of ovarian cancer in 1958. Wilkins mentioned her in passing.

In the year of receiving the Nobel Prize, Watson married Elizabeth Lewis. They had two sons: Rufus and Duncan.

Continuation of work

James Watson continued to work with many other scientists throughout the 1950s. His genius was the ability to coordinate the work different people and combine their results for new conclusions. In 1952, he used a rotating X-ray anode to demonstrate the helical structure of the tobacco mosaic virus. From 1953 to 1955 Watson collaborated with scientists at the California Institute of Technology to model the structure of RNA. From 1955 to 1956 he again worked with Crick to unravel the principles of the structure of viruses. In 1956 he moved to Harvard, where he researched RNA and protein synthesis.

scandalous chronicle

In 1968, a controversial book about DNA was published by James Watson. The Double Helix was full of derogatory comments and rancorous descriptions of many of the people involved in the discovery, especially Rosalind Franklin. Because of this, Harvard Press refused to print the book. Nevertheless, the work was published and was a great success. In a later revision, Watson apologized for his treatment of Franklin, stating that he was unaware of the pressure she faced in the 1950s as a female explorer. He profited most from the publication of two textbooks, Molecular Biology of the Gene (1965) and Molecular Biology of the Cell and Recombinant DNA (updated 2002), which are still out of print. In 2007, he published his autobiography, Avoid Boring People. Life lessons in science.

James Watson: contribution to science

In 1968 he became director of the laboratory at Cold Spring Harbor. The institute was experiencing financial difficulties at the time, but Watson proved to be very successful in finding donors. The institution headed by him has become a world leader in terms of the level of work in the field of molecular biology. Its employees uncovered the nature of cancer and discovered its genes for the first time. Every year more than 4,000 scientists from all over the world come to Cold Spring Harbor - so deep is the influence of the Institute for International Genetic Research.

In 1990, Watson was appointed director of the Human Genome Project at the National Institutes of Health. He used his fundraising abilities to lead this project until 1992. He left due to a conflict over the patenting of genetic information. James Watson believed that this would only interfere with the research of the scientists working on the project.

Controversial statements

His stay at Cold Harbor ended abruptly. On October 14, 2007, on his way to a conference in London, he was asked about world events. James Watson, a world-famous scientist, replied that he was overshadowed by the prospects for Africa. According to him, all modern social politics is based on the fact that the intelligence of its inhabitants is the same as that of the rest, but the test results indicate that this is not the case. He continued his thought with the idea that progress in Africa is hampered by poor genetic material. A public outcry against this remark forced Cold Spring Harbor to ask for his resignation. The scientist later apologized and retracted his statements, saying that "there is no scientific basis for this." In his farewell speech, he stated his vision that "ultimate victory (over cancer and mental illness) is within our grasp."

Despite these setbacks, geneticist James Watson continues to make controversial claims today. In September 2013 at the Allen Institute in Seattle, at a brain study meeting, he again made a controversial statement about his belief that the increase in diagnosed hereditary diseases could be due to later childbearing. “The older you get, the more likely you are to have defective genes,” Watson said, also suggesting that genetic material should be collected from people under 15 years of age for further conception through in vitro fertilization. In his opinion, this would reduce the chances that the life of parents will be spoiled by the birth of a child with physical or mental disorders.

English physicist (by education), Nobel Prize in Physiology or Medicine for 1962 (together with James Watson And Maurice Wilkins) with the wording: "for their discovery of the molecular structure of nucleic acids and its significance in the transmission of information in living matter."

During World War II, he worked at the Admiralty, where he developed magnetic and acoustic mines for the British fleet.

In 1946 Francis Creek read a book Erwin Schrödinger: What is life in terms of physics? and decided to leave research in the field of physics and take up problems of biology. He later wrote that in order to move from physics to biology, one must "almost be born again."

In 1947 Francis Creek left the Admiralty, and at about the same time Linus Pauling hypothesized that the diffraction pattern of proteins was determined by alpha helices wrapped one around the other.

Francis Crick was interested in two fundamental unsolved problems in biology:
- How do molecules allow the transition from non-living to living?
How does the brain think?

In 1951 Francis Creek met with James Watson and together they turned in 1953 to the analysis of the structure of DNA.

"Career F. Crick can not be called fast and bright. At thirty-five he is still Not received PhD status (PhD roughly corresponds to the title of candidate of science - Note by I.L. Vikentiev).
German bombs destroyed a laboratory in London where he was supposed to measure the viscosity of hot water under pressure.
Crick was not very upset that his career in physics had come to a standstill. He had previously been attracted to biology, so he quickly found a job in Cambridge, where his topic was the measurement of the viscosity of the cytoplasm of cells. In addition, he studied crystallography at the Cavendish.
But Crick did not have the patience to successfully develop his own scientific ideas, nor the due diligence to develop others. His constant ridicule of others, disregard for his own career, combined with self-confidence and a habit of giving advice to others, irritated his Cavendish colleagues.
But Crick himself was not enthusiastic about the scientific focus of the laboratory, which concentrated exclusively on proteins. He was sure that the search was going in the wrong direction. The secret of genes lies not in proteins, but in DNA. Seduced by ideas Watson, he abandoned his own research and focused on the study of the DNA molecule.
Thus was born a great duo of two friendly rivals: a young, ambitious American with a bit of biology, and a bright-minded but uncomposed thirty-five-year-old Briton with a background in physics.
The combination of two opposites caused an exothermic reaction.
A few months later, having put together their own and previously obtained by others, but not processed data, two scientists came close to greatest discovery throughout the history of mankind - deciphering the structure of DNA. […]
But there was no mistake.
Everything turned out to be extremely simple: DNA contains a code written along its entire molecule - an elegantly elongated double helix that can be arbitrarily long.
The code is copied due to the chemical affinity between the constituent chemical compounds - the letters of the code. The combinations of letters represent the text of the recipe for the protein molecule, written in an unknown code. The simplicity and elegance of the structure of DNA was stunning.
Later Richard Dawkins wrote: “What was really revolutionary in the era of molecular biology that came after the discovery of Watson and Crick was that the code of life was written down in digital form, incredibly similar to the code of a computer program.”

Matt Ridley, Genome: autobiography of a species in 23 chapters, M., Eksmo, 2009, pp.69-71.

After analyzing the received Maurice Wilkins data on X-ray scattering on DNA crystals, Francis Creek together with James Watson built in 1953 a model of the three-dimensional structure of this molecule, called the Watson-Crick Model.

Francis Creek wrote to his son in 1953 proudly: “ Jim Watson and i did maybe major discovery... Now we are sure that DNA is a code. Thus, the sequence of bases (“letters”) makes one gene different from another (just as different pages of printed text differ from one another). You can imagine how Nature makes copies of genes: if two chains are untwisted into two separate chains, F each chain attaches another chain, then A will always be with T, and G with C, and we will get two copies instead of one. In other words, we think we have found the underlying mechanism by which life emerges from life... You can understand how excited we are.”

Quoted in Matt Ridley, Life is a Discrete Code, in: The Theories of Everything, ed. John Brockman, M., "Bean"; "Laboratory of Knowledge", 2016, p. eleven.

Exactly Francis Creek in 1958 "... with formulated the "central dogma of molecular biology", according to which the transmission of hereditary information goes only in one direction, namely from DNA to RNA and from RNA to protein .
Its meaning is that the genetic information recorded in DNA is realized in the form of proteins, but not directly, but with the help of a related polymer - ribonucleic acid (RNA), and this path from nucleic acids to proteins is irreversible. Thus, DNA is synthesized on DNA, providing its own reduplication, i.e. reproduction of the original genetic material in generations. RNA is also synthesized on DNA, resulting in the rewriting (transcription) of genetic information into the form of multiple copies of RNA. RNA molecules serve as templates for protein synthesis - genetic information is translated into the form of polypeptide chains.

Gnatik E.N., Man and his prospects in the light of anthropogenetics: philosophical analysis, M., Publishing house Russian University friendship of peoples, 2005, p. 71.

“In 1994, a book that caused a wide resonance was published Francis Crick“An amazing hypothesis. Scientific search for the soul.
Crick is skeptical about philosophers and philosophy in general, considering their abstract reasoning unfruitful. Received the Nobel Prize for deciphering DNA (together with J. Watson and M. Wilkins), he set himself the following task: to decipher the nature of consciousness on the basis of specific facts of the brain.
By and large, he is not concerned with the question “what is consciousness?”, But how the brain produces it.
He says, "You, your joys and sorrows, your memories and ambitions, your sense of identity and free will, are really nothing more than the behavior of a vast community of nerve cells and their interacting molecules.
Most of all, Crick is interested in the question: what is the nature of the structures and patterns that ensure the connection and unity of the conscious act (“ the binding problem")?
Why are very different stimuli received by the brain connected in such a way that they eventually produce a unified experience, for example, the image of a walking cat?
It is in the nature of the connections of the brain, he believes, that one should look for an explanation of the phenomenon of consciousness.
The “surprising hypothesis”, in fact, is that the key to understanding the nature of consciousness and its qualitative images may be the synchronized bursts of neurons recorded in experiments in the range from 35 before 40 Hertz in the networks connecting the thalamus with the cerebral cortex.
Naturally, both philosophers and cognitive scientists have doubted that it is possible to build hypotheses about consciousness and its cognitive thought processes from the vibration of nerve fibers, perhaps really associated with the manifestation of phenomenal features of experience.

Yudina N.S., Consciousness, physicalism, science, in Sat.: The problem of consciousness in philosophy and science / Ed. DI. Dubrovsky, M., "Canon +", 2009, p.93.