The Hindu : Double helix

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Saturday, Mar 08, 2003

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Double helix

By N. Gopal Raj

The understanding of the DNA structure is the bedrock of modern biology. It has had a profound influence on all aspects of medicine and biotechnology.

THE APRIL 25, 1953, issue of Nature carried a brief article titled "A Structure of Deoxyribose Nucleic Acid". The article did not shake the scientific firmament. Nor did journalists rush to interview its authors, James Watson and Francis Crick, then working at the Cavendish Laboratory in Cambridge, Britain.

Today, the double helical structure of DNA proposed in that paper is often considered the most important scientific discovery of the 20th century. The acronym `DNA' is readily understood by the average person in the street, stories about gene-related research appear almost every day in the media and the double helix itself has become the easily recognised icon of the brave new age of biology.

The significance of that discovery was "perhaps not so much because of its intellectual depth or difficulty, but because of the elegance and simplicity of the solution that it provided to the problems of replication and heredity, matters that touch everyone", remarks Hugh Huxley, then a fellow researcher at Cavendish and currently at Brandeis University in the United States, writing in the latest issue of Physics World.

More importantly, the DNA structure set the stage for the revolution in genetics and molecular biology which followed. As Dr. Francis Crick was later to write, "what was important was not the way it was discovered but the object discovered". The race to find the structure of collagen was no less colourful, with G. N. Ramachandran ultimately successful with a triple helix. "Yet nobody has written even one book about the race for the triple helix. This is surely because, in a very real sense, collagen is not as important a molecule as DNA," observed Dr. Crick.

Back in 1869, Fritz Miescher had isolated an acidic substance from the nuclei of pus cells and named it `nuclein'. Sixty years later, Frederick Griffith found that a substance from heat-killed bacteria could cause hereditable changes in live bacteria.

By the early 1900s, chromosomes had been recognised as being involved in heredity. But the nature of the `gene', the most basic unit of genetic information, was far from clear. Chromosomes are a mix of DNA and various proteins. Was DNA the carrier of genes and, if so, how?

In 1944, Oswald Avery and his collaborators showed that DNA from an infectious strain of pneumococcus, bacterium that causes pneumonia, could pass on the virulence to non-infectious bacteria. But, as Maclyn McCarty, who was part of that team, wrote in a recent special issue of Nature, their findings received little acceptance. DNA was considered too limited in diversity to carry genetic information. "Even those biologists who had considered the possibility had dropped the idea, and the prevailing dogma was that if genes are composed of a known substance, it must be a protein," says Dr. McCarty.

The double helical structure proposed by Dr. Watson and Dr. Crick in their 1953 article did not win immediate acceptance. In fact, the reception from the scientific community was lukewarm.

For one thing, the scientific evidence in its favour was not that strong. As Dr. Watson and Dr. Crick themselves admitted in a journal article in 1954, the double helix they proposed "could in no sense be considered proved", although it was "most promising".

However, as they noted in their 1953 paper, the double helix structure suggested "a possible copying mechanism for the genetic material". Such exact duplication was a vital necessity for cells to replicate. The two DNA strands could separate — unzip, as it were — and each strand could act as a template for the synthesis of a new strand. Before the end of the 1950s, experimental evidence showed that this was just what was happening.

The double helix also provided the key for understanding another fundamental biological process: protein synthesis. The gene was revealed as being the sequence of four "bases" along a DNA strand which, through an intricate mechanism, determined the structure of a protein. It was these proteins which carried on life's processes. Moreover, the activity of genes has to be carefully regulated. So, in any cell, including cells of a multicellular organism which all carry the same genetic information, only some specific genes are active at any time.

"Before 1953, there was no meaningful way of even speculating about the molecular mechanisms of these two central genetic processes (DNA replication and protein synthesis)," points out Bruce Alberts, president of the U.S. National Academy of Sciences.

The understanding of the DNA structure was therefore an essential prerequisite for understanding at a molecular level how living cells replicate, differentiate, interact and respond to stimuli. In other words, it is the bedrock of modern biology. It has had a profound influence on all aspects of medicine and biotechnology.

How the DNA structure was deciphered too has been a tale of enduring fascination. After all, two young researchers were pitted against a well-established scientist. But, above all else, there is the shadow of Rosalind Franklin. There is the abiding feeling that she was denied due credit for her contributions and treated churlishly by a male-dominated scientific establishment.

At the time, few would have given Dr. Watson, then a young post-doctoral scientist in his mid-20s, and Dr. Crick, just eight years older, much of a chance when Linus Pauling was on the same quest. Just a couple of years earlier, Dr. Pauling had beaten Lawrence Bragg, director of the Cavendish Laboratory, to the alpha-helix structure of polypeptide chains. A year after the publication of the double helix structure of DNA, Dr. Pauling would be awarded the Nobel Prize in Chemistry for his work on the chemical bond.

Dr. Watson and Dr. Crick benefited from the x-ray photographs of the DNA crystal taken by Franklin. Maurice Wilkins, who was Franklin's colleague at King's College in London, and who too was working on the x-ray crystallography of DNA, had shown her x-ray photographs, without her knowledge, to Dr. Watson. Besides, another scientist showed Dr Watson and Dr. Crick her report to the Medical Research Council, giving measurements of a DNA unit cell. These two pieces of information provided vital clues about the double helical structure.

Brenda Maddox, Franklin's biographer, points out that Dr. Watson and Dr. Crick never seem to have told her what they subsequently acknowledged publicly after her death in April 1958, that her work was fundamental to their discovery. Their paper in Nature gave no hint of this. So much so that Franklin's own paper in the same issue of the journal remarks that "our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication".

In addition, Dr. Watson's account in his best-selling book, "The Double Helix", is quite offensive. "Rosie" was made out to be Dr. Wilkin's assistant who "had to go or be put in her place".

All this only served, as Ms. Maddox remarks in a recent Nature feature, to make Franklin a feminist icon. Her failure to win the Nobel Prize (awarded jointly in 1962 to Dr. Watson, Dr Crick and Dr. Wilkins) was seen as ''the entrenched misogyny of the scientific establishment, rather than the consequence of the Nobel statute against posthumous awards''.

A close friendship developed between Franklin, Dr. Watson and Dr. Crick, although she was barely on speaking terms with Dr. Wilkins. Franklin was unhappy at King's College not because of her gender, but because she was a wealthy Anglo-Jew in a Church of England setting, according to Ms. Maddox.

In the end, the entire controversy has increased awareness, among the lay public and among scientists, about Franklin's outstanding scientific contributions and her name will always be associated with the double helix.

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