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Nov 20, 2013

Frederick Sanger, Father of Genomic Era, Dies at 95

  • Frederick Sanger, the British biochemist and double Nobel Laureate whose research laid essential groundwork for the sequencing of amino acids and later DNA, has died at age 95.

    Dr. Sanger’s death was announced by The Wellcome Trust, whose director, Jeremy Farrar, hailed the sequencing pioneer as “the father of the genomic era.”

    Dr. Sanger’s sequencing work earned him two Nobel prizes in chemistry—the first in 1958 for the sequencing of human amino acids; the second in 1980 for his development of a technique to sequence human DNA. Dr. Sanger remains one of only four two-time Nobel Prize winners, and the only one from Britain.

    The first Nobel honored Dr. Sanger for sequencing insulin, developing a method of marking the end amino acid and splitting it off from the insulin. The end amino acid was then identified and the process repeated. Sanger showed that a molecule of insulin contained two peptide chains made of two or more amino acids that are linked together by two disulphide bonds. The work of identifying all 51 amino acids that make up insulin took an additional eight years.

    Dr. Sanger won his second Nobel for developing the sequencing technique that bears his name and was still being used into the 21st century. Working with Alan Coulson, Dr. Sanger pioneered a method that entails manufacturing a replica of the gene under study, then adding a specially colored “killer” chemical terminating the replication once it hits a nucleotide in the gene.

    The process is repeated with different killer chemicals which stop the replication at different sets of links, resulting in DNA fragments of varying lengths, each finishing with one of four different fluorescent dye molecules corresponding to DNA’s four nucleotides. The fragments are driven by an electric field through gel or hair-thin capillary tubes filled with polymer, enabling the sorting of the fragments by length. The emerging order of colors, which corresponds to the sequence of nucleotides in the original DNA fragment, is scanned by laser and displayed on a computer screen.

    Dr. Sanger’s method enabled the sequencing of several hundred DNA bases in a single day, rather than many years as was previously possible. Dr. Sanger and colleagues revolutionized drug and vaccine development by mapping the sequence of links of simple structures such as proteins and viruses, enhancing scientific understanding of the chemical basis of genetic defects and the processes that lead to disease.

    Dr. Sanger’s technique was applied by several makers of sequencing equipment, whose tools served as the standard until faster sequencers were developed by several instrument makers over the past decade. In 2010, for example, the U.S. Department of Energy Joint Genome Institute (JGI) held a ceremony at its Walnut Creek, CA, headquarters to mark the phase-out of the last of its Sanger sequencers after a decade’s service. JGI served as a key center for the Human Genome Project, using Sanger equipment with collaborating researchers at the Stanford Human Genome Center to decode the sequence of human chromosomes 5, 16, and 19, constituting 11% of the total human genome.

    Another key center for the genome project was the Sanger Institute named for the researcher, and established by Wellcome Trust and the U.K.’s Medical Research Council to advance knowledge in genomics. According to the BBC, when the institute’s founding director John Sulston asked Dr. Sanger if he was comfortable with the site being named after him, Dr. Sanger replied: "It had better be good."

    Born August 13, 1918, Dr. Sanger initially planned to follow his father into the medical field. The elder Sanger was the local doctor for the village of Rendcombe in Gloucester. But while attending classes at Cambridge University, Dr. Sanger opted instead for a career in research based on a growing interest in biochemistry, which he was convinced offered a way to understand many medical problems on a more scientific basis, according to Britain’s Daily Telegraph.

    Dr. Sanger retired from research in 1985 at age 65, in order to devote himself to two hobbies—tending to his garden and, as he told the BBC, “messing about in boats.” A year later in 1986, Dr. Sanger was awarded one of Britain's highest honors, the Order of Merit. But he declined a knighthood, since he did not want to be called "Sir."

    J. Craig Venter, Ph.D., this morning remembered Sanger in a Twitter tweet as “One of the most important scientists of the 20th century!”

    Dr. Venter added, “He twice changed the direction of the scientific world.”



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