Fred Sanger
Fred Sanger and his colleagues developed many of the techniques still used in genomic biology to this day. The fundamental method of 'reading' DNA using special bases called chain terminators, the use of very thin gel systems, the adaptation of efficient cloning methods to produce both DNA strands and the whole-genome shotgun were all developed by Fred and his group during the 1970s.
Fred's group produced the first DNA whole genome sequence (for a virus called phiX174 that grows in bacteria) of just over 5000 base-pairs. They went on to sequence the first human genome (albeit that of the DNA in mitochondria - small energy factories in all our cells that have their own genome of about 16,000 base-pairs) and the genome of an important virus for molecular biology, bacteriophage lambda, in 1982. To sequence this virus genome - about 48,000 base-pairs - Fred developed the whole-genome shotgun method. The sequence of lambda was the first whole-genome shotgun.
Fred was born towards the end of the First World War in Gloucestershire, UK. His father was a GP from whom he gained an interest in biology. Fred took his first degree at Cambridge University where, although originally he thought to study medicine, he specialized in biochemistry - at the time many of the world's leading biochemists were at the University.
In the 1940s and 1950s, new methods were developed in separation and purification and it seemed that it might at last be possible to determine the chemical structure of protein molecules. Over several years, Fred developed methods to determine the order (sequence) of the building blocks of the protein insulin. In 1958 he was awarded the Nobel Prize for his work in sequencing proteins. The award was a spur to his own work and moved in 1962 to the new UK Medical Research Council Laboratory of Molecular Biology, the premier institution in the world for this new science.
Surrounded by researchers interested in DNA and genes, Fred was struck by the challenge of determining the order of bases in DNA - DNA sequencing. It was by this time clear that DNA was a linear code and although the code was being unravelled, no methods existed to read the code in even the simplest genome.
Over the next 15 years, Fred and his team - amongst whom he especially mentions Bart Barrell, Alan Coulson and George Brownlee - developed several and ever-improving methods to sequence nucleic acids (DNA and RNA). The work for his second Nobel Prize (awarded in 1980) was developing the technique still used today - 'dideoxy' or 'Sanger' sequencing. In this method, stretches of 500-800 bases at a time can be read.
Fred finds it remarkable that the method he developed nearly 25 years ago is still in use today and is the method used to attack genomes as much as 3,000,000,000 base-pairs long - 500 bases at a time! Ever modest, he asserts his focus was on making the methods work and beating the problems and that larger implications seemed a long way off at the time.
He would doubtless disagree but, if anyone is the father of genomics it is this quiet, determined, modest man of strong opinions. Today he devotes his time to domestic life - especially his garden - apart from the occasional forays to the Institute that bears his name to make sure all is as it should be.
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