How DNA was discovered. When DNA was discovered The scientist who discovered the structure of the DNA molecule

30.03.2024 Complications

Penetrating deeper into the secrets of the universe, man tried to answer one of the main questions that the ancient sages asked: what is life, what is man himself? The mystery of the birth of living organisms interested scientists no less than the structure of stars. Discoveries in the field of biology made in the 20th century brought humanity to new frontiers and outlined truly fantastic prospects. Molecular biology remains one of the most promising sciences of our time.

Having developed the theory of the evolution of living organisms, Darwin could not answer the question of how changes in the structure and functions of living organisms that arose during this evolution are consolidated in the offspring. But when his book had just come out of print, Gregor Mendel was already conducting his experiments in the Czech Republic. His findings laid the foundation for the development of the science of heredity - genetics, which was destined to explain the most important mysteries of the universe. Using the pea model, Mendel first established the existence of special “hereditary factors” (later called “genes”) that are transmitted from one generation to the next, transferring certain traits. However, for a long time the transmission mechanism itself was unknown to scientists.

At the same time, zoologist August Weissmann worked in Germany, who expressed and proved the correctness of the opinion that the transfer of parental properties to offspring depends on the direct transfer by parents of a certain material substance, which, according to Weissmann, was contained in chromosomes - the organelles of the cell. The most important research for the development of genetics was later carried out by the American Thomas Morgan. Having carried out a lot of experiments on Drosophila flies, he and his collaborators came to conclusions about the material basis of heredity, the linear localization of genes in chromosomes, the patterns of their mutational variability, the cytogenetic mechanism of their hereditary transmission, etc., which made it possible to finally formalize the basic principles of the chromosomal theory of heredity.

In 1869, the biochemist Miescher isolated a hitherto unknown substance with the properties of a weak acid from cell nuclei. Later, the chemist Levin found that this acid contains the carbohydrate deoxyribose, which is why it was called deoxyribonucleic acid (DNA). In 1920, the same Levin identified four nitrogenous bases in DNA: adenine (A), guanine (G), cytosine (C) and thymidine (T). Thus, already in the 20s of the XX century. scientists knew what DNA was made of. This information was significantly supplemented in 1950 by the biochemist Chargaf, who discovered that in a DNA molecule the amount of A is equal to the amount of T, and the amount of G is equal to the amount of C.

However, as for the role of DNA in the storage and transmission of hereditary information, for a long time there were only guesses about this. In 1944, microbiologists Avery, McCarthy and McLeod were the first to transfer certain properties from one microbe to another using DNA.

And on February 28, 1953, two young scientists from the University of Cambridge, James Watson and Francis Crick, reported their discovery of the structure of the DNA molecule. They found that this molecule is a helix consisting of two chains. Each chain that has a phosphate-sugar base contains nitrogenous bases. Hydrogen bonds between A and T, on the one hand, and G and C, on the other, determine the stability of the double-helix structure. Watson and Crick determined that the sequence of nitrogenous bases in the structure of double-stranded DNA is the “code” of genetic information that is transmitted when the molecule is copied (duplicated). When two DNA chains are separated, new nucleotides can be attached to them, and a new one is formed near each of the old chains, exactly corresponding to it (since the only possible combination of nucleotides A - T, G - C).

Watson and Crick's paper, "The Molecular Structure of Nucleic Acids," was published on April 25, 1953, in the journal Nature. In the same issue, an article by London scientists R. Franklin and M. Wilkins was published, which described the results of an X-ray study of the DNA molecule, which showed that this molecule is indeed a double helix.

The discovery of Watson and Crick was recognized almost throughout the world (only the USSR was late, where genetics was defeated thanks to the efforts of Academician Lysenko). Already in 1961, American biologists Nirenberg and Ochoa established that individual sections of DNA code, that is, determine the structure of very specific protein structures (“three adjacent nucleotides code for one specific amino acid”). These scientists identified the codons corresponding to each of the 20 amino acids.

Naturally, the discovery of Watson and Crick provided only a basis for subsequent research, but without this basis genetics probably could not have developed further. In 1962, both scientists received the Nobel Prize.

In the first half of the 1970s, hybrid DNA molecules (“DNA-DNA”) were first obtained, capable of penetrating into cells of various origins and stimulating the synthesis of proteins unusual for these cells. This was the birth of a new discipline - genetic engineering, which was immediately brought under government control due to its potential use to create biological weapons. In 1977, the first version of a “machine” method for determining nucleotide sequences in a DNA molecule was developed, which sharply increased the number of uncovered (“read”) genomic regions and entire genes. In 1982, the first therapeutic agent of a new generation was obtained - genetically engineered insulin. It is produced by bacterial cells into which DNA encoding the structure of the insulin protein is injected. In 1983, a method was developed to increase the number of DNA molecules using the polymerase enzyme, and in 1985, a method of individual molecular “fingerprinting” (that is, a kind of “fingerprinting”) of each original DNA sample was developed. This made it possible to compare different DNA samples with each other to determine their identity or, conversely, dissimilarity. These methods immediately began to be used in forensic medicine to identify biological “traces of a crime”, as well as to establish paternity. New genetic engineering technology for the production of certain food products is expanding. In 2000, the human genome was almost completely deciphered. Science has come close to the possibility of determining in advance the phenotype, abilities, and pathologies of a person who is about to be born. And not only identify, but also correct, replace “sick genes” with “healthy” ones.

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 announced to a lunch crowd that they had discovered the secret of life. Many years later, Odile, F. Crick's wife, said that she, of course, did not believe him: when he came home, he often stated 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 appeared on the structure of nucleic acids. In one of them, written by J. Watson and F. Crick, the structure of the DNA molecule was proposed in the form of a double helix. The other two, written by M. Wilkins, A. Stokes, G. Wilson, R. Franklin and R. Gosling, presented experimental data confirming the helical structure of DNA molecules. The story of the discovery of the double helix of DNA 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-Resovsky, he became so interested in biology that he quit physics and became a biologist.

For a long time, in full accordance with Engels' definition of life, biologists believed that the hereditary substance was some special proteins. Nobody 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, an article by Oswald Avery, Colin McLeod and McLean McCarthy was published showing that in pneumococci, heritable 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-digesting enzyme (DNase) caused it to lose gene properties. It is still unclear why this discovery was not awarded the Nobel Prize.

Shortly before, in 1940, L. Pauling (1901–1994; Nobel Prizes 1954 and 1962) and M. Delbrück developed the concept of molecular complementarity in antigen-antibody reactions. In those 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., although it did not convince proponents of the protein gene theory, 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. for studying the crystal structure of amino acids and peptides

In 1947–1950 Based on numerous experiments, E. Chargaff established a 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 extensive experience in determining the structure of proteins from X-ray diffraction patterns, Pauling undoubtedly could have quickly solved the problem of the structure of DNA if he had had any decent X-ray diffraction patterns. However, there were none, and from those he managed to obtain, he was unable to make a clear 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 the phosphate residues form a rigid core, and the 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 get it right. He didn't read the articles or talk to anyone. Moreover, he even forgot his own paper 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 all this happened is well described in the famous book “The Double Helix” by J. Watson, although many of the facts in it are presented very subjectively.

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 without the coincidence of several coincidences, the model could have appeared several months later, and its authors could have been other scientists. Here are some examples.

Rosalind Franklin (1920–1958), who worked with M. Wilkins (Nobel Prize 1962) at King's College (London), obtained the highest quality X-ray diffraction patterns of DNA. But this work interested her little; 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, reviewing 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 structured.

X-ray of DNA obtained by R. Franklin

In an article by Wilkins et al., published in the same issue Nature The same as the paper by Watson and Crick, it is shown that, judging by X-ray diffraction patterns, the structure of DNA from different sources is approximately the same and is a helix in which the nitrogenous bases are located on the inside and the phosphate residues on the 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 helices shifted relative to each other along the axis with nitrogenous bases inside and phosphates outside. According to her data, the pitch of the DNA helix in form B (i.e., 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 a subject of study than coal and carbon, which she had studied in France before coming to King's College.

Having 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-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, despite the most friendly relations with R. Franklin, ever told her what they repeated publicly many times years after her death - 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 had lived until 1962, the Nobel Committee would have had to break its strict rules and award the prize to not three, but four scientists. In recognition of her and Wilkins' achievements, one of the buildings at King's College was named Franklin-Wilkins, forever linking the names of people who barely spoke to each other.

When reading the article by Watson and Crick (shown below), one is surprised by its small volume and lapidary style. The authors were well aware of the significance of their discovery and, nevertheless, limited themselves to only a description of the model and a brief indication that “from the postulated ... specific formation of pairs, a possible mechanism for copying genetic material immediately follows.” The model itself seemed to be taken out of thin air - there is no indication of how it was obtained. Its structural characteristics are not given, with the exception of the pitch and number of nucleotides per pitch of the helix. The formation of pairs is also not clearly described, because At that time, two systems were used for numbering the atoms in pyrimidines. The article is illustrated with only one drawing made by F. Crick's wife. However, for ordinary biologists, the articles of Wilkins and Franklin, overloaded with crystallographic data, were difficult to understand, but the article of Watson and Crick was understood by everyone.

Later, both Watson and Crick admitted that they were simply afraid to present all the details in the first article. This was done in a second paper entitled "Genetic Consequences from the Structure of DNA" and published in Nature May 30 of the same year. It provides the rationale for the model, all the dimensions and details of the DNA structure, patterns of chain formation and base pairing, and discusses 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 a year later in a methodological article they indicated that three bonds were possible. Soon Pauling 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 to read it. The question immediately arose about what the genetic code should be. The answer to this question was proposed in 1954 by 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 1958 and 1980), also working at Cambridge, developed a method for determining nucleotide sequences in DNA. Sanger used it to determine the sequence of the 5386 bases that make up the genome of bacteriophage jX174. However, the genome of this phage is a rare exception: it is single-stranded DNA.
The present era of genomes began in May 1995, when J.K. Venter announced the deciphering of the first genome of a single-celled organism - a bacterium. Haemophilus influenzae. The genomes of about 100 different organisms have now been deciphered.

Until recently, scientists thought that everything in a cell was determined by the sequence of bases in DNA, but life is apparently much more complex.
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-helical 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 had nothing to do with living organisms, but recently a group of researchers from the National Heart, Lung, and Blood Institutes (USA) discovered that one of the genes of the immune system is activated only when part of its regulatory sequence goes into Z-shape. It is now 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 lead to cell damage.

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

Last year, S. Nidle of the Institute of 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 regions of chromosomes and were called G-quadruplexes, since they are formed by regions of DNA rich in guanine.

Apparently, such structures help stabilize the DNA sections where 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 begun searching for drugs that stabilize the structure of G-quadruplexes, in the hope that they will help fight cancer.

In recent years, not only the ability of DNA molecules to form structures other than the classical double helix has been discovered. To the surprise of scientists, DNA molecules in the cell nucleus 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 sperm. However, these complexes were considered strong and static. Using modern video technology, it was possible to film the dynamics of these complexes in real time. It turns out that DNA molecules constantly form fleeting connections with each other and with various proteins that hover around DNA like flies. 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 tightly bound to the DNA molecule, dissociates and reconnects with it every minute. This inconsistency of connections helps the cell 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 vibrant life, and the well-being of the cell largely depends on the choreography of its components. Some human diseases may be caused by disruptions in the coordination of these molecular dances.

Obviously, with such an organization of the life of the nucleus, its different parts are unequal - the most active “dancers” should be closer to the center, and the least active ones should be closer 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 simply the relative position of chromosomes, apparently affects the activity of their genes. Thus, the close location 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 a cancerous one.

The past half century in biology became the era of DNA - in the 1960s. the genetic code was deciphered in the 1970s. Recombinant DNA was obtained and sequencing methods were developed in the 1980s. The polymerase chain reaction (PCR) was developed, and the Human Genome Project was launched in 1990. 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 staff of the Laboratory of Molecular Biology in Cambridge

Now, looking through the papers of Watson and Crick 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 areas 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 F. Crick published an article on the nature of consciousness in early 2003.

J.D. Watson,
F.G.K. Scream
Medical Research Council Molecular Structure Unit, Cavendish Laboratory, Cambridge. April 25, 1953

Molecular structure of nucleic acids

We want to propose a model for the structure of a deoxyribonucleic acid (DNA) salt. This structure has new properties that are of interest to biology.
The structure of the nucleic acid had 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 helix axis and nitrogenous bases at the periphery. In our opinion, this structure is unsatisfactory for two reasons. First, we believe that the material under study, which produces the X-ray reflections, is a salt and not a free acid. Without acidic hydrogen atoms, it is unclear what forces could maintain the integrity of such a structure, especially since the negatively charged phosphate groups near its axis would repel each other. Secondly, some of the van der Waals distances turn out to be too small.
Another three-stranded structure was proposed by Fraser (in press). In his model, the phosphates are on the outside, and the nitrogenous bases, connected to each other by hydrogen bonds, are inside the helix. This structure is defined very poorly in the article and for this reason we will not comment on it.
We want to propose a radically different deoxyribonucleic acid salt structure. 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 axis of the spiral. Both chains form a right-handed spiral, but, thanks to the dyads, they have opposite directions. Each strand is slightly reminiscent of Ferberg's Model No. 1 in that the bases are located on the inside of the helix and the phosphates 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 located approximately perpendicular to its associated base. The residues on each chain are located in increments of 3.4 A in the direction z. We assumed that the angle between adjacent 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 phosphates are located outside, they are easily accessible to cations.
The entire structure is open and contains quite a lot of water. As the water content decreases, you can expect the bases to tilt somewhat and the entire structure to become more compact.
A new 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 spiral. They are connected in pairs, with one base on the first chain hydrogen bonded to one base on the second chain such 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 the 1 position of purine and the 1 position of pyrimidine and between the 6 position of purine and the 6 position of pyrimidine.
It is assumed that the bases enter this structure only in their most likely tautomeric form (i.e., keto rather than enol form). It has been discovered that only specific base pairs can form bonds with each other. These pairs are as follows: adenine (purine) - thymine (pyrimidine) and guanine (purine) - cytosine (pyrimidine).
In other words, if adenine is one member of a pair on any chain, then by this assumption the other member of the pair must be thymine. The same applies to guanine and cytosine. The sequence of bases on one chain appears to be unlimited. However, since only certain base pairs can be formed, given the base sequence of one chain, the base sequence of the other chain is determined automatically.
It has been experimentally discovered 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 impossible to build such a structure with ribose instead of deoxyribose, because the additional oxygen atom makes the van der Waals distance too small.
The X-ray diffraction data on deoxyribonucleic acid published to date are insufficient to rigorously test our model. As far as we can judge, it approximately corresponds to experimental data, but it cannot be considered proven until it is compared with more accurate experimental data. Some of them are given 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 primarily, but not exclusively, on published experimental data and stereochemical considerations.
It should be noted that from the specific pair formation we postulated, a possible mechanism for copying genetic material immediately follows.
All details of the structure, including the conditions necessary for its construction and 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 stimulated by a general understanding of the 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 Foundation for Infantile Paralysis.

* Georgy Antonovich Gamov (1904–1968, emigrated to the USA in 1933) - 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-droplet model of the atomic nucleus - the basis of theories of nuclear decay and thermonuclear reactions; the theory of the internal structure of stars, which showed that the source of solar energy is thermonuclear reactions; the “Big Bang” theory in the evolution of the Universe; theories of cosmic microwave background radiation in cosmology. His popular science books are well known, such as the series of books about Mr. Tompkins (Mr. Tompkins in Wonderland, Mr. Tompkins Inside, etc.), One, Two, Three... Infinity, A Planet Called Earth " and etc.

The materials in the section used articles and notes from the following publications: “Economist” and “New Scientist” (England), “American Scientist”, “Discover”, “IEEE Spectrum”, “Science News”, “Scientific American Mind”, and “Wired” "(USA), "Ça m'interesse", "Ciel et Espace", "Le Journal du CNRS", "La Recherche" and "Science et Vie" (France), as well as press agency reports and information from the Internet.

Friedrich Miescher in the last years of his life.

The University of Tübingen houses a test tube containing the DNA isolated by Miescher.

As a rule, the names of the English biologists J. Watson and F. Crick, who discovered the structure of this molecule in 1953, are associated with the DNA molecule. However, the connection itself was not opened by them. But the discoverer is not mentioned in every reference book or textbook.

Deoxyribonucleic acid was discovered in 1869 by a young Swiss doctor, Friedrich Miescher, who was then working in Germany. He decided to study the chemical composition of animal cells, and chose leukocytes as the material. These germ-eating protective cells are abundant in pus, and Miescher enlisted the cooperation of colleagues at a local surgical hospital. They began bringing him baskets with purulent bandages removed from his wounds. Miescher tested different methods of washing leukocytes from gauze bandages and began to isolate proteins from the washed cells. During his work, he realized that in addition to proteins, leukocytes contain some mysterious compound. It precipitated in the form of white flakes or threads when the solution was acidified and dissolved again when it was made alkaline. Examining his leukocyte preparation under a microscope, the scientist discovered that after washing the leukocytes from the bandages with dilute hydrochloric acid, only nuclei remained. And he concluded: the unknown compound is contained in the nuclei of cells. Miescher called it nuclein, from the Latin nucleus - nucleus.

At that time, almost nothing was known about the cell nucleus, although three years before Miescher’s discovery, in 1866, the famous German biologist Ernst Haeckel suggested that the nucleus was responsible for the transmission of hereditary characteristics.

Wanting to study nuclein in more detail, Miescher developed a procedure for its isolation and purification. Having treated the sediment with enzymes that digest protein, he was convinced that it was not a protein compound - the enzymes were unable to decompose nuclein. It did not dissolve in ether and other organic solvents, that is, it was not a fatty substance. Chemical analysis was then extremely labor-intensive, slow and not very accurate, but Miescher carried it out and became convinced that nuclein consisted of carbon, oxygen, hydrogen, nitrogen and large quantities of phosphorus. At that time, organic molecules with phosphorus in their composition were practically unknown. All this convinced Miescher that he had discovered some new class of intracellular compounds.

Having written an article about the new discovery, he sent it to his teacher, one of the founders of biochemistry, Felix Hoppe-Seyler, who published the journal Medico-Chemical Research. He decided to check such an unusual message in his laboratory. The verification took a whole year, and Miescher was already afraid that someone would independently discover the same nuclein and publish the results first. But in the next issue of the magazine for 1871, Miescher’s article was accompanied by two articles by Hoppe-Seyler himself and his collaborator, confirming the properties of nuclein.

Returning to Switzerland, Miescher took up the post of head of the department of physiology at the University of Basel and continued his research on nuclein. Here he found another rich and more pleasant source of a new compound - the milt of salmon fish (they are still used for mass production of DNA). The Rhine, which flows through Basel, was then full of salmon, and Miescher himself caught hundreds of them for his research.

In an article on the discovery of nuclein in milk, published in 1874, Miescher wrote that this substance is clearly associated with the process of fertilization. But he rejected the idea that hereditary information could be encoded in nuclein: the compound seemed to him too simple and uniform to store the entire variety of hereditary characteristics. The analysis methods of that time did not allow us to find significant differences between human and salmon nuclein.

Later, Miescher studied the physiology of salmon, developed a cheap and healthy diet for prisons at the request of the Swiss government, wrote a cookbook for workers, founded the Institute of Anatomy and Physiology in Basel, studied the role of blood in the respiration process... Even during his lifetime, nuclein was renamed “ nucleic acid,” which greatly irritated the discoverer. Miescher died of tuberculosis in 1895. For almost half a century after his death, it was believed that the DNA molecule, consisting of only four types of blocks, was too simple to store hereditary information, and much more diverse proteins were put forward for this role.

Nucleic acids were first discovered in the nucleus of human cells by Swiss researcher Friedrich Miescher in 1869. At the beginning of the 20th century, biologists and biochemists managed to figure out the structure and basic properties of the cell. It has been discovered that one of the nucleic acids, DNA, is an extremely large molecule made up of structural units called nucleotides, each containing nitrogenous bases.

Maurice Wilkins and Rosalyn Franklin, scientists from the University of Cambridge, conducted X-ray structural analysis of DNA molecules and showed that they are a double helix, reminiscent of a spiral staircase. The data they obtained led the American biochemist James Watson to the idea of ​​studying the chemical structure of nucleic acids. The National Society for the Study of Infantile Paralysis provided a grant. In October 1951, at the Cavendish Laboratory at the University of Cambridge, Watson began studying the spatial structure of DNA together with John C. Kendrew and Francis Crick, a physicist who was interested in biology and was writing his doctoral dissertation at the time.

Watson and Crick knew that there are two types of nucleic acids - deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), each of which consists of a pentose monosaccharide, phosphate and four nitrogenous bases: adenine, thymine (in RNA - uracil), guanine and cytosine. Over the next eight months, Watson and Crick combined their results with those already available and, in February 1953, reported on the structure of DNA. A month later, they created a three-dimensional model of the DNA molecule, made from balls, pieces of cardboard and wire.

According to the Crick-Watson model, DNA is a double helix consisting of two chains of deoxyribose phosphate connected by base pairs similar to the rungs of a ladder. Through hydrogen bonds, adenine combines with thymine, and guanine with cytosine. Using this model, it was possible to trace the replication of the DNA molecule itself. According to Watson and Crick, two parts of a DNA molecule separate from each other at hydrogen bonding sites, much like undoing a zipper. From each half of the previous molecule, a new DNA molecule is synthesized. The sequence of bases functions as a template, or template, for the formation of new DNA molecules. The discovery of the chemical structure of DNA has been hailed throughout the world as one of the most outstanding biological discoveries of the century.

DNA plays an extremely important role in both the maintenance and reproduction of life. Firstly, it is the storage of hereditary information, which is contained in the nucleotide sequence of one of its chains. The smallest unit of genetic information after a nucleotide is three consecutive nucleotides - a triplet. Triplets located one behind the other, determining the structure of one chain, constitute a so-called gene. The second function of DNA is the transmission of hereditary information from generation to generation. DNA participates as a matrix in the process of transferring genetic information from the nucleus to the cytoplasm to the site of protein synthesis.

Watson, Crick and Wilkins received the 1962 Nobel Prize in Physiology or Medicine "for their discoveries about the molecular structure of nucleic acids and for their identification of their role in the transmission of information in living matter." In a speech at the presentation, A. W. Engström of the Karolinska Institute described DNA as “a polymer composed of several types of building blocks - monosaccharide, phosphate and nitrogenous bases... Monosaccharide and phosphate are the repeating elements of the giant DNA molecule, in addition, it contains four type of nitrogenous bases. The discovery is the order in which these building blocks are spatially connected.”

What has this discovery changed in our lives over the past 50-plus years??

In 1969, scientists first synthesized an artificial enzyme, and in 1971, an artificial gene. At the end of the 20th century, it became possible to create completely artificial microorganisms. Thus, artificial bacteria were created in laboratories that produce unusual amino acids, as well as viable “synthetic” viruses. Work is underway to create more complex artificial organisms - plants and animals.

The study of the structure and biochemistry of DNA led to the creation of techniques for genome modification and cloning. In 1980, the first patent was issued for experiments with mammalian genes, and a year later a transgenic mouse with an artificially modified genome was created. In 1996, the first cloned mammal, Dolly the sheep, was born, followed by cloned mice, rats, cows and monkeys.

In 2002, the Human Genome Project was successfully completed, during which a complete genetic map of human cells was created. And in the same year, attempts at human cloning began, although none of them have been completed yet (at least, there is no scientific evidence of successful human cloning).

Back in 1978, insulin was created, almost completely identical to human insulin, and then its gene was introduced into the genome of bacteria, which turned into an “insulin factory.” In 1990, a gene therapy method was first tested, which saved the life of a four-year-old girl who suffered from a severe immune disorder. Nowadays, the study of the genetic mechanisms of the development of a variety of diseases - from cancer to arthritis - and the search for methods for correcting the genetic “errors” that cause them are in full swing. In total, more than 350 drugs and vaccines are used in clinical practice, the creation of which uses genetic engineering.

DNA analysis has found wide application even in forensic science. It is used during trials to recognize paternity (by the way, this method has become a real gift for musicians, politicians and actors who were forced to prove in court their non-involvement in the birth of children attributed to them), as well as to establish the identity of the criminal. It is worth noting that James Watson himself spoke about such a possibility of using DNA, proposing to create a database that would include the personal DNA structures of all the inhabitants of the planet, which would speed up the process of identifying criminals and their victims.

Using DNA, you can “catch” not only criminals, but also, for example, drugs or biological weapons. American criminologists are using a system to monitor the DNA structure of drug plants to create a database of all varieties of marijuana. This database will allow you to track the source of almost any drug sample. In the near future, DNA analysis-based methods for detecting biological attacks will begin to be used in the United States - it is planned to install special sensors in public places that will automatically “catch” dangerous microorganisms from the air and give a warning signal.

In 1982, the first successful modification of a plant genome was carried out. And five years later, the first agricultural plants with a modified genome appeared in the fields (these were tomatoes resistant to viral diseases).

Nowadays, almost all food products are grown using genetic engineering, especially crops such as soybeans and corn. Since 1996, when commercial use of genetically modified foods began, the total area under crops has increased 50-fold. The total area under transgenic crops in the world in 2005 was 90 million hectares. True, the governments of many countries have banned the cultivation and import of such products, since a number of studies have shown that they can pose a danger to human health (allergies, damage to reproductive function, etc.).

The ability to study the structure of DNA has given new impetus to historical research. For example, the remains of Nicholas II and his family were identified, and some historical gossip was confirmed and refuted (in particular, it was proven that one of the founders of the United States, Thomas Jefferson, had illegitimate children from a black slave).

Using DNA analysis, it was possible to trace the origins of both people and entire nations. For example, it has been shown that the genes of the Japanese are almost identical to the genes of one of the Central American tribes. And for just $349, black Americans can find out what region of Africa and even what tribe their ancestors, brought on slave ships many years ago, came from.

What will DNA give us in the near future??

Obviously, this will be the cloning of a person and his organs, which will solve the problem of the shortage of donor hearts and lungs for transplantation. New drugs will appear that will make incurable genetic diseases a thing of the past...


More than fifty years ago a remarkable scientific discovery was made. On April 25, 1953, an article was published about how the most mysterious molecule, the deoxyribonucleic acid molecule, works. It is called DNA for short. This molecule is found in all living cells of all living organisms. Scientists discovered it more than a hundred years ago. But then no one knew how this molecule was structured and what role it played in the life of living beings.

The English physicist Francis Crick and the American biologist James Watson managed to finally solve the mystery.
Their discovery was very important. And not only for biologists, who finally learned how the molecule that controls all the properties of a living organism is structured.
One of the largest discoveries of mankind was made in such a way that it is completely impossible to say which science this discovery belongs to - chemistry, physics and biology merged so closely in it. This fusion of sciences is the most striking feature of the discovery of Crick and Watson.

History of the discovery of DNA

Scientists have long been interested in the secret of the main property of all living organisms - reproduction. Why do children - whether we are talking about people, bears, viruses - look like their parents and grandparents? In order to uncover the secret, biologists studied a variety of organisms.

And scientists have found that special particles of a living cell - chromosomes - are responsible for the similarity of children and parents. They look like little sticks. Small sections of the rod chromosome were called genes. There are a lot of genes, and each is responsible for some characteristic of the future organism. If we talk about a person, then one gene determines the color of the eyes, another determines the shape of the nose... But what the gene consists of and how it is structured, scientists did not know. True, it was already known: chromosomes contain DNA and DNA has something to do with genes.

Different scientists wanted to solve the mystery of the gene: each looked at this mystery from the point of view of their science. But in order to find out how a gene, a small particle of DNA, is structured, it was necessary to find out how the molecule itself is structured and what it consists of.
Chemists who study the chemical composition of substances studied the chemical composition of the DNA molecule. Physicists began to x-ray DNA, just as they usually x-ray crystals, to find out how these crystals are structured. And they found out that DNA is like a spiral.

Biologists were, of course, most interested in the mystery of the gene. And Watson decided to tackle the gene problem. In order to learn from advanced biochemists and learn more about the nature of the gene, he traveled from America to Europe.
At that time, Watson and Crick did not yet know each other. Watson, after working for some time in Europe, made no significant progress in elucidating the nature of the gene.

But at one of the scientific conferences he learned that physicists are studying the structure of the DNA molecule using their own physical methods. Having learned this, Watson realized that physicists would help him uncover the secret of the gene, and went to England, where he got a job in a physics laboratory in which biological molecules were studied. This is where the meeting between Watson and Crick took place.

How the physicist Crick became interested in biology

Crick was not at all interested in biology. Until he came across a book by the famous physicist Schrödinger, “What is life from the point of view of physics?”

In this book, the author suggested that a chromosome is like a crystal. Schrödinger noticed that the “reproduction” of genes resembles the growth of a crystal, and suggested that scientists consider a gene a crystal. This proposal interested Crick and other physicists. That's why.

A crystal is a very simple physical body in structure: the same group of atoms is repeated in it all the time. And the structure of the gene was considered very complex, since there are so many of them and they are all different. If genes consist of the substance DNA, and the DNA molecule is structured in the same way as a crystal, then it turns out that it is both complex and simple. How so?
Watson and Crick understood that physicists and biologists know too little about the DNA molecule. True, chemists knew something about DNA.

How Watson helped chemists, and chemists helped Scream

Chemists knew that the DNA molecule contains four chemical compounds: adenine, thymine, guanine and cytosine. They were designated by the first letters - A, T, G, C. Moreover, there was as much adenine as thymine, and guanine as cytosine. Why? Chemists could not understand this.

They guessed: it had something to do with the structure of the molecule. But they didn’t know how. The chemists were helped by biologist Watson.
Watson was accustomed to the fact that in living nature many things are found in pairs: a pair of eyes, a pair of hands, a pair of legs, there are, for example, two sexes: male and female... It seemed to him that a DNA molecule could also consist of two chains. But if DNA is like a spiral, as physicists have discovered using X-rays, then how do the two strands hold each other together in this spiral? Watson suggested that with the help of A, G, C and T, which, like hands, are extended to each other. Having cut out the outlines of these chemical compounds from cardboard, Watson spent a long time applying them this way and that, until he suddenly saw: adenine combines perfectly with thymine, and guanine with cytosine.

Watson told Crick about this. He quickly figured out what the double helix should look like in reality - in space, and not in the picture. Both scientists began to build a model of DNA.
What does it mean to “build”? That's how. From a molecular construction set that resembles a children's construction toy. In the molecular constructor, the parts are balls-atoms, which are fastened to each other with buttons in the order in which the atoms are located in the substance.

The molecular designer was invented by another scientist - chemist Pauling. He built models of protein molecules and found out that they must have regions similar to helices. Very soon this was confirmed by the physicists of the laboratory where Crick worked. An important biological problem was solved theoretically.

Crick liked Pauling's method so much that he suggested that Watson build a model of DNA using a molecular constructor. This is how the model of the famous DNA Double Helix was created, which you can see in the picture.
And what’s remarkable: due to the fact that A in one chain can “stick together” only with T in another, and G only with C, the “chemical” rule is automatically fulfilled, according to which the amount of A is equal to the amount of T, and the amount of G is equal number of C. But the most important thing is that, looking at the Double Helix of DNA, it is immediately clear how to solve the riddle of gene reproduction. It is enough to “unwind” the DNA braid, and each chain will be able to complete a new one on itself so that A is glued to T, and G is glued to C: there was one gene - there are two. Due to the fact that the sizes of the A-T and G-C pairs are the same, the DNA molecule actually resembles a crystal in structure, as physicists assumed.

And at the same time, this “crystal” can contain very different combinations of A, T, C, G, and therefore all genes are different.
The solution to the gene problem by Watson and Crick led to the formation of a whole new field of natural science in just 2–3 years, which was called molecular biology. It is often called physical-chemical biology.

Importance of DNA discovery

The question of what and how is written in DNA has accelerated the deciphering of the genetic code. The realization that genes are DNA, the universal carrier of genetic information, led to the emergence of genetic engineering. Today, university students are already deciphering the alternation of nucleotides in DNA, connecting genes of different organisms, transferring them between species, genera and much more distant taxa. On the basis of genetic engineering, biotechnology arose, which the famous science fiction writer S. Lem defined as the use of the laws of biogenesis in production.

Let us remember what V.L. said about the nature of genes. Johannsen, the man who in 1909 gave the very name of the gene: “The properties of organisms are determined by special, under certain circumstances separable from each other and therefore to a certain extent independent units or elements in the germ cells, which we call genes.

Since then the situation has changed significantly. We are convinced that there is nothing in the cell except atoms and molecules. And it obeys the same physical laws as inanimate objects, as physicists who rushed into biology in the 40s were able to verify precisely in search of some fundamentally new laws of nature unknown to physics. All reactions of cellular metabolism are carried out under the control of biocatalysts - enzymes, the structure of which is recorded in the DNA of genes. This record is transmitted in the information transfer chain DNA RNA PROTEIN.

First, information recorded in the form of alternating deoxyribonucleotides on one of the two complementary chains in the DNA of a gene is copied onto a single-stranded molecule of informational ribonucleic acid - mRNA (also known as mRNA from the English messenger - carrier). This is the process of transcription. At the next stage, the sequence of amino acid residues of the polypeptide is constructed from the mRNA matrix. This creates the primary structure of the future protein molecule. This is the translation process. The primary structure determines the way the protein molecule is folded and thereby determines its enzymatic or some other, such as structural or regulatory, function.

These ideas originated in the early 40s, when J. Beadle and E. Tatum put forward their famous slogan “One gene - one enzyme” *. He, like political slogans, divided the scientific community into supporters and opponents of the hypothesis about the equality of the number of genes and the number of enzymes in the cell. The arguments in the discussion that arose were the facts obtained during the development of the so-called gene-enzyme systems, in which mutations of genes were studied, their location within genes was determined and changes in the enzymes encoded by these genes were taken into account: replacement of amino acid residues in their polypeptide chains, their effect on enzymatic activity etc. We now know that one enzyme can be encoded in several genes if it consists of different subunits, that is, different polypeptide chains. We know that there are genes that do not encode polypeptides at all. These are genes encoding transfer RNAs (tRNAs) or ribosomal RNAs (rRNAs) involved in protein synthesis.

In its original form, the principle of “One gene - one enzyme” is rather of historical interest, but deserves a monument, since it stimulated the creation of an entire scientific field - comparative molecular biology of the gene, in which genes - units of hereditary information appear as independent subjects of study.