Fred Sanger, Double Nobel Laureate: A Biography, by George G. Brownlee. 2014. Cambridge University Press

George Brownlee, the author of this book, joined Fred Sanger as a research student in 1963 in the then new MRC Laboratory of Molecular Biology in Cambridge. Fred had decided to start work on sequencing nucleic acids and Brownlee was asked to try to purify phenylalanine transfer RNA. The transfer RNAs were chosen because they were small molecules and could be purified from natural sources. Although he failed in this task, Brownlee continued working on sequencing methods using the 5S RNA of E. coli, which could be labeled with radioactive phosphate and the relatively small amounts easily purified. In his previous work, Fred had tried to develop radioactive methods for sequencing proteins because these methods reduced the amount of pure material required for the task. He knew that only a few proteins were available in the gram quantities required for the methods he developed with insulin. Furthermore, the protein could be labeled with radioactive tags, which allowed limited radioactive sequencing of peptides produced by enzymatic fragmentation.

A good deal of this biography is based on almost verbatim interviews of Fred Sanger which George Brownlee made in 1992, about a decade after Fred had retired. The interviews cover his early life, his work on insulin in the Biochemistry Department for which he won his first Nobel Prize (1958, Chemistry, for his work on the structure of proteins, especially insulin), and his work in the MRC Laboratory of Molecular Biology on sequencing RNA and DNA for which he was awarded his second Nobel Prize (1980, Chemistry, jointly with Paul Berg and Walter Gilbert, for contributions to the determination of sequences in DNA). The book also has five commentaries by other scientists and an introduction by Ed Southern; all emphasize how Fred Sanger revolutionized the whole field of biological research by his inventions and discoveries. As Paul Nurse states, “Fred is one of those few individuals of whom it can be said that they changed the world for ever.”

Fred Sanger was a unique scientist who worked at the bench right up to the end. However, like all good inventors, he did not try to invent everything, but used what was available in novel ways. Thus his work on insulin depended on the invention of paper chromatography by Martin and Synge, and the dideoxy method could not have been implemented without the powerful technique of acrylamide gel electrophoresis. Although his proof that proteins had a defined chemical structure was one of the cornerstones for what became molecular biology, Fred did not take the step himself; the revolution was created by Watson and Crick in 1953 with the discovery of the double-helical structure of DNA, with the complementary pairing of the bases.

The intellectual drive for the creation of molecular biology did not come from biochemistry but from genetics. It led to the concept of biological information encoded in the sequence of bases in DNA and its translation through a complementary sequence of mRNA into the sequence of amino acids in proteins following the genetic code. By 1962, when Fred joined the new Laboratory of Molecular Biology, most of the basic problems set by the new science had been solved, and it was therefore natural for him to choose nucleic acids for his next work. The Laboratory of Molecular Biology had a unique culture, and it was called a Laboratory rather than a Unit or an Institute because it was a place where everybody worked at the bench; even Francis Crick put on a white coat when he tried to purify transfer RNA and when he worked on frameshift mutants. Because it derived from the Perutz and Kendrew group in the Cavendish Laboratory with a long tradition of developing the methods for protein crystallography, it had a culture that valued and appreciated new techniques. Fred fit this culture well and he found many other scientists who very quickly recognized and appreciated what he was doing and applied his methods to solve important biological problems. In these days of heavily managed scientific research, it is hard for the bureaucrats of science to understand self-disciplined freedom in scientific research and the great benefits it can bring not only to science but to all humanity.

Sydney Brenner, Institute of Molecular and Cell Biology, Singapore 138673; e-mail: sydney.brenner@hotmail.com