Meet your genetics father

Francis Crick
January 5, 2007

Francis Crick was the person who did most to unravel the genetic code and to establish its importance. His work laid the foundations of molecular biology, which has already made unique contributions to subjects as varied as the treatment of disease, forensic science and studies of evolution. As a small boy growing up in rural England, Crick was fascinated by the unexpected findings of science that he read about in Arthur Mee's Children's Encyclopedia . He began to worry that all of science's mysteries would have been solved by the time he could start his research career. Matt Ridley portrays the life, work and beliefs of this remarkable man who journeyed to the peak of scientific achievement.

Crick was born into a middle-class family that had made a good income in the shoe trade, for which Northampton was renowned. He won a scholarship to Mill Hill School in north London, where he was considered to be an average student. He then studied physics at University College London, where he earned a rather poor second-class degree. Supported by money from an uncle, he began a PhD project in physics that was interrupted by the onset of the Second World War. This limited academic success certainly did not foretell the scale of his later achievement.

Throughout the book, Ridley places great emphasis on Crick's ability to analyse a situation clearly. This skill was in evidence in his efforts to develop a means to sink specialised German minesweepers. Intelligence from occupied territory reported that these ships had powerful electromagnets in their bows to detonate the British mines harmlessly in front of the ship.

To the consternation of naval officers, Crick reasoned counterintuitively that a less sensitive mine would not explode until the magnet was overhead, but he needed information about the strength of the magnet and speed of the boat to design such a mine. Fortunately, this became available from two reconnaissance photographs showing a mine exploding and the ship passing through the resulting plume of water. The mines that were designed did not sink normal ships, but they destroyed many of the special minesweepers.

Towards the end of the war, Crick changed the direction of his research from physics to biology. He re-educated himself by reading widely and attending lectures about chemistry and biology. He won a Medical Research Council scholarship and set out in search of a laboratory. At this point, he met Maurice Wilkins, who was at the new biophysics laboratory at King's College London and who was to remain a friend for life. But the leader of the lab, John Randall, refused to accept Crick. Finally, he was offered a position at the Strangeways Laboratory in Cambridge. There he was able to begin his pursuit of the fundamental difference between living and non-living materials.

Ridley makes the strong point that throughout his long career Crick was most effective when he had a close colleague and sparring partner with whom he first developed new interpretations and then dismissed them in vigorous debate. These theories, which were always based on experimental observations, provided the basis for more analysis. Three people were particularly important in this role at different times in his life: Jim Watson, Sidney Brenner and Christof Koch.

The story of how Crick and Watson stumbled upon the structure of DNA has been retold many times. As is often the case, progress in research depended on contributions from people with different expertise and experience.

Ridley describes the significant contributions made by others, especially those made by Rosalind Franklin and Wilkins before he makes the crucial point that Watson and Crick were the only potential partnership to work well together.

In their 1953 publication describing the structure of DNA, the authors mentioned in passing that the method of replication was apparent from the nature of the double helix. By contrast, it was to take 13 years to understand how the DNA sequence directed production of a specific protein.

Initial proposals assumed that the amino acids were themselves bound to the nucleotides in the DNA before being joined in a new peptide strand. We now know that specialist molecules made up of ribonucleic acid are involved in the process of protein synthesis. Three "letters" of the DNA (or RNA) chain specify each amino acid.

The period after the discovery of DNA's structure was one of experimentation and analysis, and Crick played a leading role. The atmosphere at the time was different from that which would generally apply today. There certainly was competition between the groups, as there would be now, but communication among them was far more open. Key players were invited to join the "RNA tie club". In those days, long before e-mail, communication was often in letters, some of which are still in existence and are referred to by Ridley. This must have been a potent and exciting environment, and one in which progress might well have been much quicker than is possible now.

In most aspects, the central role played by Crick in understanding these mechanisms was as chief sceptic, but he carried out crucial experiments to discover how many DNA letters are used to specify each amino acid. Brenner was the key partner in these experiments - he shared Crick's office for 20 years and it seems that they were well-matched debaters.

These experiments used the group of viruses that attack bacteria. Single mutations introduced into the DNA of such viruses by chemical mutagens were often lethal. But two mutations sometimes cancelled one another out. Crick and Brenner reasoned that one might delete a nucleotide while the other added one. Hence the cumulative effect was to cancel one another out so that the virus produced a functional protein. They then hypothesised that if the number of adjacent mutations was the same as the number of nucleotides (letters) needed to specify an amino acid, then in that case the virus might also be able to form a functional protein. Ridley recounts Crick's excitement and satisfaction on completion of that study. Crick wrote the key paper to Nature.

The "central dogma" of cell biology, which is taken for granted by modern students, was hotly contested for many years after it was first put forward by Crick at a meeting of the Society for Experimental Biology in England in 1957. This was some years before the facts were fully established. It was he who summarised the information first for an audience in the Royal Society in London and later at Cold Spring Harbor, on Long Island, New York.

The final research subject to attract Crick's attention was the nature of "consciousness". A number of factors made Crick and his wife of many years, Odile, choose to make their home in California. Crick had been a visiting fellow at the Salk Institute, near San Diego, for several years, but in 1977 he was offered a generously endowed permanent position. There he built up a close working relationship with his third sparring partner, Koch, an energetic, smart physicist from the American Midwest. He resembled Crick at a younger age, in his energy, ambition and determination. They worked closely until Crick's death at the age of 88.

Almost to the end of his life, Crick continued to develop new ideas, to share them with others and to subject his thoughts and those of others to the sharpest of critical assessment. He and Koch put forward the suggestion that the claustrum, a region of the brain that has particularly extensive connections, might be the seat of consciousness. Sadly, he did not live to see the idea tested.

Apart from science and his family, mention is made of visits to the London theatres and of frequent, very lively parties that were sometimes enlivened by special themes. At different times, he and Odile lived on a boat moored on the Greek island Spetsai, in an English country cottage and later in a home that Crick designed himself in the desert, inland from San Diego.

Ridley, who is a biologist by initial training and a distinguished writer in the field, presents the science very clearly. He has drawn on a wide range of documents and personal interviews to provide a detailed and more balanced record than in some earlier accounts. This book more than meets the aim of the publisher's Eminent Lives series in providing "an ideal introduction" to Crick and to the history of this aspect of molecular biology.

Crick emerges from the biography as a man who had prodigious powers of concentration, who sifted information from an extremely wide range of sources and who disciplined his thinking. Apparently, he learnt from Georg Kreisel, a wartime friend and mathematical logician, not to indulge his early taste for "wit and paradoxes in the style of Oscar Wilde". Later friends remark on his ability for abstract thought and analysis. In particular, he could visualise the 3-D structures of the materials being studied. His contribution certainly warrants the claim that was made at his memorial ceremony, and is repeated by Ridley, that he was the greatest biologist of the 20th century.

Ian Wilmut is director of the Centre for Regenerative Medicine, Edinburgh University.

Francis Crick: Discoverer of the Genetic Code

Author - Matt Ridley
Publisher - Harper
Pages - 213
Price - £12.99
ISBN - 0 00 721330 1

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