October 07, 2006

The Structure of DNA

James D. Watson and Francis H. C. Crick, Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid, 1953

Rosalind E. Franklin and R. G. Gosling, Molecular Configuration in Sodium Thymonucleate, 1953

The discovery of the structure of DNA marks a branching point in the study of genetics. From then on, one branch studied DNA at the molecular level, unravelling the way it controls living cells, a matter of chemistry as much as anything, and a second branch continued to study the effects of genes and their spread through populations, relying heavily on statistics. Of course, the real picture isn't so simple. Both types of biologist existed before 1953, and individuals who work on both levels contiue to be common. Nonetheless, Watson, Crick, and Franklin managed, through their unveiling of one of evolution's most elegant creations, to trigger a flood of new research into molecular genetics.

As discussed last time, before 1953 scientists already knew quite a lot about the location of genetic information on the chromosomes in cell nuclei. In 1928 Fred Griffith showed that exposing a harmless type of bacteria to the heat-killed remains of a virulent variant could transform them into the virulent form, and concluded that some genetic information must be passed from the dead bacteria to the living. In 1944 Oswald Avery and his colleagues separated dead virulent bacteria into some component substances, including proteins, fats, carbohydrates, DNA, and RNA, then tested all these substances on living non-virulent bacteria. The results showed that DNA is the substance that transforms the benign bacteria, and therefore caries genetic information.

The chemical components of DNA, namely deoxyribose (a five carbon sugar), phospate groups, cytosine, thymine (both single ringed nitrogen compounds), adenine, and guanine (double ringed nitrogen compounds), had been known since the 1920s. Not known was the way these six components were connected together and arranged in three dimensions.

So, by 1950, determining the structure of DNA had become a competitive goal for many scientists. In the UK, Maurice Wilkins had been working on DNA for years, and was so involved that Watson said that in 1950 the study of DNA in England was "for all practical purposes the property of Maurice Wilkins." In the USA, Linus Pauling (The Chemical Bond) was also working to figure out the structure of DNA, and in early 1953 he actually proposed a model, which soon turned out to be incorrect (triple-stranded, phospate groups in the core).

Rosalind Franklin, working in the same laboratory as Maurice Wilkins, discovered that his sample of DNA contained two separate forms, which was making analysis of their structure difficult. She carefully created pure samples of both forms and was able to get clear look at them through X-ray diffraction.

Meanwhile, Watson and Crick, a pair of ambitious scientists at nearby Cambridge Laboratory, were undeterred by the stiff competition and were working hard to figure out the structure of DNA before the competition could. Crick had worked out the mathematics of X-ray diffraction pictures of helical molicules, so when Watson saw Franklin's results, they screamed "Helical molecule!" at him.

Among other methods, Watson and Crick were cutting out cardboard and metal models of the six components of DNA and trying to fit them together in plausible ways. It was in the course of messing about with these models that they figured out the correct structure: two long strands of alternating deoxyribose and phosphate groups, with rungs connecting the strands formed by adenine-thymine (A-T) or guanine-cytosine (G-C) pairs, and the whole thing twisted into a helical structure. Much of this had already been worked out, but the key contribution was the unique paring of the nitrogen compounds, which guaranteed that all the rungs of the ladder would be the same length.

Only afterwards did they find a key bit of supporting evidence: in 1950, chemist Erwin Chargaff had found that the amounts of A and G in DNA were equal to the amounts of T and C respectively!

DNA, then, is actually two very long molecules that are held together by small amounts of charge on the atoms in the "rungs" (which are actually split down the middle). As a result, it is relatively easy to "unzip" the DNA into two parts. Also, DNA is composed of one of four repeated parts (a deoxyribose, a phospate group, and one of the four rung compounds). When a single strand of unzipped DNA is put into a solution containing these components, the free-floating components will quickly stick to the appropriate places on the DNA, and, with a little help from enzymes, can be attached to each other to form a complete copy of the opposite strand! This is the method by which genetic information is copied into every cell in our body.

Only five years later, Rosalind Franklin died, at the age of 37, of ovarian cancer. Four years after that, Watson, Crick, and Wilkins were awarded the Nobel Prize in Medicine. It is possible that had Franklin lived, she would have been awarded the Nobel instead of Wilkins (Nobels cannot be awarded posthumously).


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