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Crick and Watson's DNA Model
From: Science Museum | By: Ann Newmark

EDITOR'S INTRODUCTION | The discovery of the structure of deoxyribose nucleic acid (DNA) by Francis Crick and James Watson in 1953 was one of the most significant scientific advances of the twentieth century. The breakthrough did not come easily--Crick and Watson endured a number of problems and setbacks in their quest for the solution. Ann Newmark, Head of Documentation at the Science Museum, charts the progress of a discovery that has had such enormous implications.


e wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest." So began the short letter to Nature in 1953 announcing one of the most far-reaching discoveries of this century, the solving of the structure of DNA, the stuff of which genes are made.


Biotechnology and genetic engineering, sciences that have developed so dramatically in the latter part of the twentieth century, owe their origins to this understanding of the structure of DNA and the ability to manipulate it. metal plate Disease resistant crops, specially designed drugs, scientific testing procedures, even treatments for hereditary illnesses have now become possible through these technologies. One of the most ambitious projects of the twentieth century is to map the entire human genome--to determine the genetic code of DNA in man.


In 1951 a young American research worker, James Watson, joined Francis Crick at the molecular biology unit at Cambridge University. Both were motivated by a growing conviction that the genetic material was DNA, and were determined to discover how its structure could enable it to pass on information from one generation to the next. It was already known that DNA was made up of long chains of alternating sugar and phosphate groups with further chemical groups (bases) attached to each sugar, but how were these long chains arranged in space?


The chief experimental evidence was emerging from the Medical Research Council unit at King's College London where Maurice Wilkins and Rosalind Franklin were using the well-established technique of X-ray diffraction to study DNA's structure. When X-rays are shone on to substances, such as crystals, which contain regular arrangements of atoms, some rays are deflected and form characteristic patterns of spots on a photographic plate. Analysis of such patterns had led to the solution of many crystalline structures over the previous three decades. The fibrous structure of DNA also gave characteristic X-ray diffraction pictures indicating the presence of regular arrays of atoms.


Crick had previously shown, mathematically, that diffraction patterns of a helix (a corkscrew shape) took the form of a cross. replicaThe diffraction patterns obtained from DNA fibres by Rosalind Franklin showed just such a cross shape, convincing Crick and Watson that DNA was helical. However it was not possible to obtain the complete structure directly from the early X-ray data so Crick and Watson turned to model building in the hope that this intuitive approach might produce a structure compatible with both the X-ray data and the known chemical structure.


In their haste to be the first to solve the structure, they produced a model containing three helical molecules of DNA at the end of 1951. Wilkins and Franklin travelled from London to Cambridge to see it and, to Crick and Watson's chagrin, proceeded to demolish their arguments supporting this structure. During 1952 Linus Pauling at Caltech in California also turned his attention to DNA. Having already discovered helical structures in proteins, he started building models of DNA, producing another triple helix structure towards the end of 1952. To Watson and Crick's enormous relief, this too was shown to be wrong. The race was still on. During 1952 Franklin produced her superb pictures of a second form of DNA. From these it was deduced that the structure must contain two chains. It was Crick who then realized that Franklin's analysis indicated that the two chains ran in opposite directions.


The final breakthrough came when they considered some chemical evidence provided by Erwin Chargaff. Four different chemical groups, or bases, could be attached to the sugar groups of the backbone; Chargaff had discovered that amounts of two bases, adenine and thymine, were always identical, he also found that the amounts of the two other bases, guanine and cytosine, were also equal. Watson realized that because of their shape and chemical nature these two pairs of bases could be arranged with very weak bonds holding them together (so-called hydrogen bonds). The shape of each pair was almost identical and would fit down the centre of a double helix formed by the two backbone chains.


Crick and Watson lost no time in building their model, using the metal plates now in the Science Museum, to represent the four bases. This time there was no mistake and in the words of Max Perutz, the then director of the Laboratory of Molecular Biology, "1953 became the annum mirabilis. The Queen was crowned; Everest was climbed; DNA was solved."


The elegant structure proposed offered an immediate explanation of how genetic information contained in DNA could be copied and passed from one generation to the next. The weak hydrogen bonds between each pair of bases which hold the two strands of the double helix together are easily broken. Each strand then acts as a template for building new molecules. The specific pairing of the bases ensures that each new chain is an exact replica of the original. Crick concluded his letter to Nature with the words: 'It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.'


In 1962 James Watson and Francis Crick received the Nobel Prize for Medicine together with Maurice Wilkins. Tragically Rosalind Franklin, whose beautiful X-ray diffraction pictures had provided key evidence, had died nearly five years earlier. By this time Crick had already started on his seminal work in unravelling the genetic code, enabling us to understand how DNA specifies the structure of the proteins it is programmed to make.