James Watson and Francis Crick with their model of DNA structure. Having your article published in 1953, they received the Nobel Prize for medicine and physiology in 1962. The most influential and elegant scientific work of the twentieth century was published in the journal Nature on April 25, 1953 and has little more than a single page.
When Watson and Crick began their studies on the structure of DNA, both had read the classic book of Schrodinger titled "What's life " or "What is life." In this work, the theoretical physicist Erwin Schrodinger austíaco (1887-1961) tried to explain, using only concepts from physics and chemistry, as might be encoded and transmitted to heredity in living organisms. The idea of \u200b\u200bvitalism , that biological organisms were composed of a kind of magical force, the élan vital , had long lost strength and Schrodinger's book, published in 1944, was just an attempt to explain the heredity without resorting to any remnant of this exciting magic of living forces which was used as an explanatory model for life in ancient Greece.
In his book, Schrodinger argued that the gene should be understood as a molecule, a molecule that it was as big and stable like a crystal. She, however, could not be just as well organized and hard as a crystal for a very simple reason: she needed to store information, biological information for cellular function and heredity. A crystal is well known, is a set of molecules highly ordered and that, in order so precise and repetitive, is not able to save complex forms of information. A salt crystal, for example, has no information and is simply an organization specifically set up of atoms sodium and chlorine. It's like the classic crystal consisted of a single phrase repeated millions of times chemical, such as Na-Cl. To form a chemical-informational book of life, we need to have several sentences containing different senses, semantic complex formula to end all the information necessary for life to happen and be passed on. The genetic material of a cell must be able to "organize" and keep life, and move to the next generation information on the life she has coordinated for some time. Since much is already known that children resemble their parents and that somehow this information is passed along the generations when the evolutionary process. Just do not know how this happened and even before the studies of Mendel, who revealed the gene while the particle, believed in the inheritance model for mixture, where characteristics of the offspring were simply explained by a mixture of characteristics from parents. Mendel showed that there were dominant and recessive traits and that, somehow, inheritance functioned largely as hereditary particles (genes) and not as complete mixes of features, and thus rejected the thought of "by blending inheritance." But nobody could explain so far as this trait heritable, genetic, was transmitted across generations. Schrodinger was the first to say that this genetic information should be encoded in chemical form, in some kind of organic molecule. There would thus any kind of spirit or magical power to govern the inheritance and he tried to find something physical, a molecule that would dismiss all this information. For Schrodinger, the molecules more suitable for storing information would be a polymer molecule and rigid structure, like a crystal. Nevertheless, the crystals were then known as simple and rigid structure, which could not store information in any complex known form. The gene, then concludes Schrodinger, must be a type of molecule that is an aperiodic crystal ; crystal without a period - or repeating forms - precisely defined, a regular molecule enough to store information in a precise but irregular enough to contain regions informational rather than a full repetition of non-informative patterns.
The Austrian physicist Erwin Schrodinger (1887-1961). Being best known for having developed an equation that describes how the quantum state of physical systems evolve through time, Schrodinger also assisted the development of molecular biology to theorize about a molecule capable of carrying genetic information. This aperiodic crystal turned out to be as the DNA, after the studies of Watson and Crick. One of the founders of quantum mechanics and one of the most brilliant theorists of the twentieth century, Schrodinger questioned the science of his time and produced ideas and paradoxes often poorly understood by science, as the idea that Schrodinger's cat can be alive and dead at the same time .
Schrodinger's contribution, important, assembled and prepares the theoretical basis for the discovery of DNA, but at no time the left for a physical observation of natural molecules so as to suggest any of them as more likely to carry such information. The biologists, however, regarded as the protein molecules more likely to transmit information. This happened simply because they were the most studied molecules at the time, known while presenting many beautiful and striking features - such as enzymes ferment - that it was a pretty big leap to imagine them also to observe the code of heredity . Nevertheless, no one had managed to prove that they would be responsible for containing this information and many suspected of other organic molecules as more likely to carry the code for evolution.
Watson recounts in one of his texts: " From the day of our first meeting, Crick and I think it would be highly likely that genetic information was encoded by the DNA sequence of four bases " [1]. Therefore, the ideal of researchers have started from the idea that it was possible to produce a model of the molecular structure of DNA where information contained was just following the four bases. It was known that DNA consisted of nucleotides that they had two stable parts (phosphate and ribose) and a part that was different for each class of nucleotides. Such chemical differences of the bases would produce different nucleotides (A, C, G and T) and were the only possible variations in these molecules. Watson and Crick, from the first moment, brilliantly pulled the informational code for life should come from the formation of "chemical phrases" DNA. Each gene was thus composed of regularly ordered sets of bases, as ACGGTTCAGATCGAT where the order of the basis function as the order of letters / characters in any language, like Portuguese or English. The information would be for the gene sequence of bases as well as information contained in one word would be in its sequence of letters or characters constituents. The information would come from the DNA sequence of letters and, somehow, the cell would be able to read, process and pass on this information. They "only" needed to know how this would happen.
is important to note that until this moment, the structure was known to the DNA structure proposed by the Russian doctor Phoebus Levene [2] that, by 1910, had discovered that DNA was composed of nucleotides that differed mainly by nature of their bases. Levene has even proposed a structure for the DNA molecule. For him, however, DNA consisted of a simple molecule composed of four nucleotides linked together without the possibility of any variation capable of storing information. If DNA is indeed present in this way, he could not form long molecules (polymers [3]) and could not keep the information required. According to François Jacob, in his excellent book, "The logic of life" at the time the " nucleic acid appears as a molecular species without variety or fancy, and therefore without the ability to play any role in heredity. Thus, it is attributed role this protein, although its properties lend themselves poorly to it . "Jacob continues," Due to its complexity, heredity seems to be beyond the reach of experimental chemistry . "[4]
molecular diagram of a hypothetical tetranucleotide, as proposed by Phoebus Levene incorrectly by around 1910. If the DNA was the case, could not form long molecules (polymers) and could not hold hereditary information. Thus, it was initially discarded as responsible for this function.
The structure of DNA seconds Levene ( 1869-1940), therefore, lacked the necessary characteristics to convey information. As the amount observed for each of the nucleotides of DNA was very close, Levene thought the single molecule to form a tetramer of nucleotides comprising a quality of each base (A, C, G and T), where the bases were joined together by carbon 3'OH. Although incorrect, the structure of Levene is very smart and stylish. However, by not forming a polymeric molecule (read: large) or aperiodic, it could not load information. In the first half of the twentieth century, the very Levene was the first to defend that nucleic acids could not carry information since it had a very simple structure. Thus, most genius in chemistry of nucleic acids, the discoverer of the ribose (1909), deoxyribose (1929) and own units of nucleotides (DNA monomer) said that these molecules did not carry information. Who would be crazy enough to disagree with him? But
Levene died in 1940 and Watson and Crick seemed to have already dismissed all other possibilities of how molecules responsible for the transmission of heredity. Moreover, as the experiments of Avery, McLeod and McCarthy (1944), as well as Hershey and Chase (1952) demonstrated the role of DNA as the carrier of genetic information. The experiment of Avery and colleagues, although hard evidence that the DNA molecule would have been responsible for genetic transmission was placed in doubt by several scientists. Among them, the main Alfred Mirsky was the U.S. which suggested that the experiment of Avery was contaminated with protein. Later Mirsky was against the suggestion of Nobel winner for Avery, and it was only after Watson and Crick that DNA was really taken by the community as the true carrier of genetic information.
As already mentioned, the first meeting since Watson and Crick, there was already agreement about the fact that genetic information should derive from a non-random sequence of nucleotides containing bases ordered. Now they needed "only" get a model whereby all this became clear as the base sequence was available in space precisely, they wanted to find a structure to verify that his deep feeling that the code would be prepared this way.
is worth noting that the famous figure produced in the laboratories of Rosalind Franklin (1920-1958) at King's College London (Watson and Crick worked in Cambridge) stated there is not much. It merely indicated that the DNA has a helical structure, but did not explain anything about how the nucleotides would be willing to form structure. In fact, if such a micrograph of the X-ray diffraction of DNA explain anything directly, Rosalind would have been to discover the structure of the molecule, and not Watson and Crick.
Famous autoradiography of the DNA molecule. Produced by the laboratory of Rosalind Fraklin in London, was supposedly "stolen" by Watson. The picture, however, does not solve the problem of the structure of the molecule, it just shows that the molecule appeared to have a helical shape. But how would that propeller? As it would be mounted? How does she convey the inheritance?
To get an idea of \u200b\u200bhow the autoradiogram molecule is not as informative about the model, Linus Pauling published a structure of DNA in triple helix based on similar data (though lower quality), in February 1953. Pauling's model, released about two months before the model of Watson and Crick, was simply incorrect.
Watson and Crick, however, came slowly accumulating new information that helped them build the accurate model of DNA structure. They agreed that the molecule should forward information from the sequence of bases from the experimental data and knew that she should have a helical shape. And what's more, they still had some other highly sensitive information significant [5]: *
Astbury proposed that DNA was a long linear molecule;
* Maurice Wilkins had experiments that said, in a single crystal of DNA, there should be two or three molecules;
* Chargaff shown that the amount of nucleotides was similar to the T, and the number of nucleotide G was similar to C - even before that, it was thought, with Levene, the proportion of all bases was identical;
* John Griffith suggested the idea of \u200b\u200bpairing A = T, G = C. With inheritance
Schrödinger, yet they knew that the DNA molecule should be able to form some crystal type and thus should be regular, but not very regular, so that he could not contain information. However, if the molecule should be regular in some region, it should be fairly regular in the regions of similarity between the nucleotides. Being composed of phosphate, ribose and bases, nucleotides that formed the nucleic acid molecules were identical in the region of phosphate and (deoxy) ribose , differing in chemical bases. Thus the molecule could be quite regular in consecutive order and composition of the nucleotides with respect phosphate and ribose. Moreover, the sequence of bases would be what would contain information that could provide structure and slightly irregular, being responsible for storing and transmitting information. Watson says that this thinking led them to believe that the skeleton invariant phosphate-ribose molecule should be contained in the center of the molecule [4]. Linus Pauling thought so too, so that its structure is the skeletons had triple ribose-phosphate in the center and bases abroad. (In the correct model, which were the bases pareavam internally in the molecule.)
Watson decided to design and build atomic models of the bases to try put them together spatially by following the rule of Chargaff (A = T, G = C) and the next day, when its results showed Crick realized that this pairing would remain valid even if the bases were switched around. This meant that the tape could be in one or the other and still pair with T, one on each side of the tape. However, even if the physical and chemical fit precisely with T, G = C pair is not formed properly. In a lecture on the discovery of the structure of DNA, Watson advises, "never be the smartest person in a room" [5]. When in doubt about how the pairing would occur between G and C, Watson turned to the researcher that there had been published the latest chemical structure to the nucleotide guanosine (G). Jerry Donahue complained that the structure described for the guanine base was a problem for the assembly of the model that had been trying to solve. By showing then the model for the researcher, Donahue said the hydrogens were placed in different locations, wrong, guanine was once published in its keto form, which hampered the pairing with cytosine. But the form aldol was also probable, possible and considered by some to be more correct. He was trying to fit with the new cytosine guanine Watson's eyes sparkled and he had finally found the pairing of DNA bases! "And then we knew we had something great, you know, because if The places you near the T and G near the C, you have a copy mechanism. Thus we saw how genetic information is encoded in the form of four bases, and therefore a kind of digital information, "Watson says in his TED conference [6].
The structure of DNA as suggested by Watson and Crick. ribose-phosphate skeleton form the rigid structure of the molecule. At the center, the nitrogen bases bind according to the Watson-Crick pairing, A = T / G = C. The two strands of DNA molecules are antiparallel, one phosphate present in the top end, another at the bottom. The chemical structure originally published for the nucleotide guanine (G) did not allow a perfect fit in the physical-chemical cytosine (C) and had to rearrange the theory to adapt it to the Watson-Crick structure.
The discovery of the pairing of bases, associated with the phosphate-ribose skeleton, allowed now that DNA could be described as a large polymeric molecule that is. Consisting of fact, two molecules that twist, the structure of DNA could now be properly explained. Each of the molecules was formed by a rigid skeleton of phosphate and ribose which were, in fact, the outer side of the molecule. The bases are pareariam inside of it, in the Watson-Crick pairing always done precisely between varieties A = T and G = C. Each of the tapes of the DNA molecule would contain all information required to encode the life and thereafter it became clear that DNA replication happen in a semi-conservative. The tapes would separate and - since each one would contain all the necessary information - the DNA could be duplicated to form the new strands from existing ones. Molecular mechanisms would be responsible for separating the DNA strands and by adding new nucleotides to go to the tapes newly synthesized. Where there was in the old tape, it would add a new T to. With the Watson-Crick pairing was unclear how the DNA replication happen and this would have shown a simple idea, sleek and shiny. In fact, most scientific idea and the most beautiful theoretical model of science in the twentieth century.
semi-conservative replication of the DNA molecule. Having defined the precise pairing of base pairs and understood that the skeleton was formed by a DNA sequence phosphate-ribose, automatically the way it was explained replication of the molecule. The model, therefore, was not only coherent, its empirical content was so well established that the mere observation of it has allowed several other mechanisms were understood clearly and directly. The new DNA molecules were produced as of old, which functioned as a template for the synthesis of new tapes. The double strand is separated and each of the single strands that previously constituted was used as a template for making new DNA. Where there was one in the old tape, it would add a new T to. The Watson-Crick pairing (A = T, G = C) explain replication effectively.
Over the decades that followed, the Watson-Crick model for the structure of DNA provided a strong, accurate and valuable tool for the development of the science of molecular biology . In the years that followed were discovered (i) the functions of RNA, (ii) the genetic code, (iii) precisely how they operate ribosomes and (iv) how the DNA information was directed to the synthesis of proteins. This new evidence led to the maturation of molecular biology as a theoretical model for the coordination of intracellular functions and heredity. Around 1968, enzymes that allow the cutting and assembling pieces of DNA were also found and provided the foundation for genetic engineering and transgenesis. But those are stories for other traces of philosophy, allow me now I will do a little epistemological analysis of these developments.
== epistemological analysis of the findings of Watson and Crick: Duhem and anomalies retrospectively ==
"Pierre Duhem was a physicist and philosopher of science Frenchman who lived between 1861 and 1916. For Duhem, a scientific theory consists of a set of statements and presents empirical consequences (EC) (...) Duhem states that the refutation of an empirical result does not necessarily refute the theory. Since the theory is composed of a set of statements, some of them can it be false - and thus some fireworks ad hoc can be used to explain the falsity location and save the theory. The crux of the matter is related to the fact that in an experiment, you never know exactly what you are testing a theory and is always tested in blocks and is tied to a particular set of assumptions. "(Prosdócimo, 2007) [7]
This was the introduction that the Duhem I gave two years ago. And if I come here again to talk about it, it's because they've introcedeu my way while studying the intellectual history of molecular biology . The following example will show that clarifies somewhat the model of development of science Duhemian .
is interesting to note in the story above described mainly as the new theory of Watson and Crick allowed a re-accommodation of knowledge previously already described without their thoroughly refuted. The very structure of DNA Levene was not wholly incorrect. Levene agreed that the nucleotides are linked through the phosphate and ribose, he just could not imagine a large polymeric molecule containing thousands or millions of nucleotides linked together. To Levene, DNA was a molecule like aspirin, or an inert molecule and need, not something capable of forming a long chain where its small variations of nitrogen bases form a code for chemical-informational heredity. In fact, this is a very elegant idea that needed to be built slowly developing and scientific way of doing science by researchers. In fact, the Watson-Crick paper was not immediately hailed as revolutionary, it took some years until the model was fully understood and taken as correct - the Nobel Prize has been granted only nine years after the original publication in 1962. Only with the later developments of the research in molecular biology and verification of its efficiency as an explanatory model, as well as their fertility research program is giving high status to the researchers as having done some of the greatest achievements in the history of science in the century XX.
is interesting to note how epistemological theories rely excessively on the complete deconstruction of knowledge of the past - or the refutation of theories - to build new theories. I believe this example demonstrates that the evolution of science is more related to a new accommodation of existing data according to a new perspective or logic of seeing the world. I believe it is this accommodation of old facts to new evidence or theoretical models that promotes scientific revolutions. The anomaly does not exist in order to disprove something that has ceased to exist, but the fault is actually in partial or inaccurate description of an empirical question - as in fact that the structure of the Levene or the description of chemical model of guanine. Seated under new theoretical presuppositions facts and assumptions previously held as true are able to adjust to a new theory that has been reasonably well developed, but ran up against this anomaly. The anomalous data when corrected and reinterpreted confirms efficacy and elegance with a new theory. The pairing of bases and empirical consequences arising from the same permitted a reformulation of old skills which are now totally adapted to a new coherent theoretical model.
The task of the creative scientist, like Watson and Crick seems to be first place: a theory reasonably well assembled and then seek to find evidence in the scientific knowledge itself well to corroborate that. Normally such evidence would not be "formatted" for this new thinking, but can be re-interpreted in light of new theory, giving it more strength as a theoretical model of description of nature. The anomaly, therefore, often only perceived a posteriori, ie when there is already a new model which requires the reformulation of certain old skills.
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[1] Watson, JD. Early Speculations and Facts about RNA Templates, 1993 (p. 24). In: The Passion for DNA: Genes, genomes and society. 252p.
[2] Phoebus Aaron Levene T (1869-1940) was a Russian doctor who was eradicated in the U.S. around 1893. Working at the Rockefeller Institute, NY, he discovered the ribose (1909) and deoxyribose (1929). It was also he who suggested the structure of nucleotides as phosphate-sugar-base.
[3] A polymer consists simply of a large molecule formed by the union of several small molecules, called monomers. DNA, for example, is a polymer of nucleotides, while the protein is a polymer of amino acids and glycogen is a polymer of glucose. Analogously it may be said that a pearl necklace of pearls is a polymer.
[4] Jacob, François. The logic of life. 2001. GRAIL PUBLISHING. Original French edition published in 1976 .
[5] Linus Pauling and the race for DNA. Developing an Idea of \u200b\u200bthe DNA Structure. (1:38) James D. Watson http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/dna/video/1973v.3-irregular.html
[6] TED talk: James Watson speaks about the structure of DNA. http://www.ted.com/talks/james_watson_on_how_he_discovered_dna.html
[7] Prosdócimo, 2007. The Duhem-Quine thesis. Series: epistemology of science. I bring a philosophy blog, http://tragodefilosofia.blogspot.com
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