The Hindu Business Line : The stuff of life: Crick's legacy

LAST month, Francis Crick, who helped discover the structure of deoxyribonucleic acid (DNA), died of colon cancer in San Diego, US. Crick and his colleague James Watson are to life-sciences what Edmund Hillary and Tensing Norgay are to the Mount Everest.

In 1953, in a paper which began with a typically British understatement, the epoch-making discovery of the DNA structure was announced by Francis H. C. Crick and James D. Watson: "We wish to suggest a structure for the salt of deoxyribonucleic acid. This structure has novel features which are of considerable biological interest."

In fact, so central is DNA to biology that the names of Crick and Watson may be remembered as long as those of Darwin and Mendel, the architects of the two pillars of modern biology: The theory of evolution and the laws of genetics.

Francis Harry Compton Crick was born on June 8, 1916, in Northampton, England, where his father and uncle ran a shoe factory founded by their father. He took a degree in Physics at University College, London, and after a short period, was drawn by the Second World War into military research, working on the design of magnetic and acoustic mines. He did so well at this that after the war, Dr R. V. Jones, head of Britain's war-time scientific intelligence, wanted Crick to succeed him. But, fortunately for the future of biology, Crick chose research.

Finding himself at a loose end after the war, Crick decided the most interesting research problem lay in trying to understand the physical basis of life, the division between the living and the non-living. This eventually drew him to the Cavendish Laboratory in Cambridge, one of the world's leading centres for studying the structure of proteins by X-ray analysis. At 35, he started working for his Ph.D. on the structure of proteins. Well before his thesis on the structure of haemoglobin was finished, he realised that a far more interesting problem was the structure of DNA.

A classic experiment of 1944 had pointed to DNA as the genetic material but biologists had made almost no progress since then in understanding how the hereditary information might be stored. One October 1951 day, a 23-year-old American biologist, James Watson, walked into Crick's life. Neither was supposed to be working on DNA, but they at once fell into discussing how the problem might be approached. They teamed up and soon so animated became their discussions that the pair was given their own small office at the Cavendish Laboratory so their voices would not disturb everyone others.

To understand the progress of science, we must go back to the late 19th century, when a German biochemist found that the nucleic acids — long-chain polymer of nucleotides — were made up of sugar, phosphoric acid, and several nitrogen-containing bases. Later, it was found that the sugar in nucleic acid can be ribose or deoxyribose, giving two forms: RNA and DNA.

In 1943, American Oswald Avery proved that DNA carries genetic information. He even suggested that DNA might actually be the gene. Most people at the time thought the gene would be protein, not nucleic acid, but by the late 1940s, DNA was largely accepted as the genetic molecule. Scientists still needed to figure out this molecule's structure to be sure, and to understand how it worked.

In 1948, Linus Pauling discovered that many proteins take the shape of an alpha helix, spiralled like a spring coil.

In 1950, biochemist Erwin Chargaff found that the arrangement of nitrogen bases in DNA varied widely, but the amount of certain bases always occurred in a one-to-one ratio. These discoveries were an important foundation for the later description of DNA.

In the early 1950s, at King's College in London, Maurice Wilkins and Rosalind Franklin were also studying DNA. While Crick and Watson were making physical models to narrow down the possibilities and eventually create an accurate picture of the molecule, the King's College team took an experimental approach, looking particularly at X-ray diffraction images of DNA.

The discovery of DNA was not without its share of drama. First came the controversy surrounding the treatment meted out to Rosalind Franklin although everyone now acknowledges that but for her diligent work in X-Ray crystallography, Crick and Watson could not have announced their greatest triumph when they did.

In 1951, Watson attended a lecture by Franklin on her work to date. She had found that DNA can exist in two forms, depending on the relative humidity in the surrounding air.

This had helped her deduce that the phosphate part of the molecule was on the outside. Watson returned to Cambridge with a rather muddy recollection of the facts Franklin had presented. Based on this information, Watson and Crick made a failed model. At one stage, the head of their unit had to tell them to stop DNA research.

Franklin, working mostly alone, found that her X-ray diffractions showed that the `wet' form of DNA (in the higher humidity) had all the characteristics of a helix. She suspected that all DNA were helical but did not want to announce this finding until she had sufficient evidence on the other form as well. Maurice Wilkins was frustrated.

In January 1953, he showed Franklin's results to Watson, apparently without her knowledge or consent. Crick later admitted, "I'm afraid we always used to adopt — let's say, a patronising attitude towards her."

Watson and Crick took a crucial conceptual step, suggesting the molecule was made of two chains of nucleotides, each in a helix as Franklin had found, but one going up and the other down. Crick had just learned of Chargaff's findings about base pairs in the summer of 1952. He added that to the model, so that matching base pairs interlocked in the middle of the double helix to keep the distance between the chains constant. Watson and Crick showed that each strand of the DNA molecule was a template for the other. During cell division the two strands separate and on each strand a new "other half" is built, just like the one before. This way DNA can reproduce itself without changing its structure — except for occasional errors or mutations.

The structure so perfectly fit the experimental data that it was almost immediately accepted. DNA's discovery has been called the most important biological work of the last 100 years, and the field it opened may be the scientific frontier for the next 100. By 1962, when Watson, Crick, and Wilkins shared the Nobel Prize for physiology/medicine, Franklin had died.

In his memoir, Crick said: "It is true that by blundering about we stumbled on gold, but the fact remains that we were looking for gold. Both of us had decided, quite independently of each other, that the central problem in molecular biology was the chemical structure of the gene."

No other scientists were pursuing the structure with such single-mindedness.

After making the discovery and completing the requirements for his Ph.D., Dr Crick plunged into the problems now made accessible by the new structure.

How does the sequence of bases in DNA determine the sequence of amino acids in the ribbon-like structure of each protein molecule? How is the information copied from DNA and transferred to the cell's protein-synthesising centres? Though many scientists played important roles in solving this array of problems, the guiding intelligence at almost all points was Crick's.

It was he, for example, who first realised there could be only a specific number of amino acids, the building blocks of proteins. Scanning the confused biochemical literature, he drew up the list of the 20 acids.

With his colleague Sydney Brenner, Crick eventually proved, in an experiment of remarkable elegance, that the genetic code was a comma-less, triplet code in which sets of three bases in the DNA sequence determine a corresponding sequence of amino acids in proteins.

In a conversation in 1960 with the French biologist François Jacob, Crick and Brenner recognised the long-puzzling identity of the messenger chemical, now known as messenger RNA, that distributes copies of the genetic information in the cell's nucleus to the protein-making apparatus in the cell's periphery.

In another remarkable insight, Crick in his "adaptor hypothesis", divined that there must exist both a class of carrier molecules that recognise triplets on the messenger and adaptor enzymes that link each kind of amino acid to its appropriate carrier.

Biochemists ridiculed the idea, saying that if the adaptor enzymes existed, they would already have found them. But both the transfer RNA's and the adaptor enzymes proved to exist, as Crick had predicted.

Crick derived several theories that have stood the test of time. He assumed from the start that the genetic code was universal to all forms of life, as indeed with trivial exceptions it has proved to be. His "central dogma" formulated the view that once genetic information has passed into protein, it cannot get out again.

The dogma meant that the genetic message is impenetrable by information from outside the cell, thus excluding the Lamarckian thesis that acquired characteristics can be inherited.

In 1977, Crick moved to the Salk Institute in La Jolla, Calif. There he took on another challenging unsolved problem of biology — the nature of consciousness. He had little expectation of producing any radically new ideas at his advanced age of 72, he wrote in 1988, "but at my time of life I had a right to do things for my own amusement".

Never one to let his mind lie fallow, Crick produced a stream of papers about aspects of the brain and a well-regarded popular book The Astonishing Hypothesis (1994), which summarised his ideas. Dr Crick's style of practising science was unusual. Most biologists do experiments; he did so very rarely, being one of biology's few theoreticians. He did not take graduate students, preferring instead to work with a single colleague.

Crick wrote little about his own life and, despite his fame, remained a surprisingly private person. He has a son Michael through his first wife Ruth Doreen Dodd divorced in 1947 and two daughters Gabrielle and Jacqueline from his second wife Odile Speed.

More Stories on : People | Science & Technology | Bio-tech & Genetics

Article E-Mail :: Comment :: Syndication :: Printer Friendly Page

Stories in this Section
Shadow-boxing in BPO taxation

Inflation overhang — No room for complacency

Capacity constraints keep crude prices high

Caesar's wife

WTO framework for global trade — Farm sector can grow without subsidies

The stuff of life: Crick's legacy

Empowering the commodity economy