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Winning two Nobel Prizes, turning down knighthoods: The legacy of Fred Sanger (1918-2013)

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Fred Sanger (1918-2013) (Image: The Telegraph)

British biochemist Fred Sanger died today at 95. He’s the only person to win two Nobel Prizes in chemistry, an achievement that is unlikely to be surpassed anytime soon. In his full but not overly long career – promptly ending with retirement at the mandatory retirement age in Britain – Sanger revolutionized both protein sequencing and DNA sequencing. Both the modern proteomics and genomics revolutions stand on his shoulders. And in a discipline whose major upheavals have traditionally been tool-driven rather than idea-driven, Sanger was among the very best of tool makers.

What was the secret to his success? In what is probably the only autobiographical article he ever wrote (Annu. Rev. Biochem., 1988, 57, 1) , Sanger provides a valuable clue:

“Of the three main activities involved in scientific research, thinking, talking and doing, I much prefer the last and am probably best at it. I am all right at the thinking, but not much good at the talking.”

It was this trait that made the technically brilliant and exceedingly soft-spoken and modest Sanger almost as unrecognized among the general public as he was recognized among his peers. Sanger’s lack of recognition is a ringing criticism of both the public’s adulation of people who talk more as well as the relative neglect of experimentalists who are adept at building things with their hands. In the 1950s when the very identity of proteins was unclear, Sanger came up with a simple chemical method for identifying individual amino acids in a protein or peptide by tagging them with a brightly colored chemical handle. The first protein whose sequence he unravelled – insulin – was both a revelation and a technical tour de force. Combined with Linus Pauling’s work on delineating the basic structure of proteins, Sanger essentially set protein science on a rational basis.

This achievement would have been enough to ensure him a place in history. Astonishingly enough, he followed up with a second act. In the 1970s when the details of genetics were being worked out and refined, Sanger created an even more elegant and ingenious method for sequencing the bases of DNA. The method hinged on the existence of “chain terminating” groups of bases that would essentially allow scientists to read the sequence of a stretch of DNA by tagging incremental fragments of the DNA with these terminating groups and then separating them with an electric field on a gel. The result was clear as day; by knowing the basic rules for complementary base pairing (A-T, G-C), you can literally read out the sequence of the DNA by looking at adjacent lanes on the gel. Using the method in 1977, Sanger read the 6000 base pair genome of the virus Phi X 174, a stupendous achievement for the time.

Sanger sequencing became the basis of every sequencing endeavor during the next 25 years including the Human Genome Project. Today it’s being surpassed by so-called “Next-Gen” methods but it’s quite clear that none of the early success could have come without Sanger’s advance (another method developed by Sanger’s fellow Nobel Prize winner Wally Gilbert is more tedious and was deprioritized). Sanger is as much the father of genomics as are Watson and Crick.

Along with his superior craftsmanship, it was Sanger’s unerringly quiet, modest and intensely dedicated personality – partly arising from his Quaker roots – that undoubtedly contributed to his great success. His parents died when he was an undergraduate, an event that must surely have contributed to his serious pursuit of scientific truth. In a way Sanger was the Paul Dirac of chemistry; technically brilliant, wedded to his work, reserved to a fault, averse to teaching and administration, a scientist’s scientist in every way. Unlike most scientists who are content with directing the careers of their students after a certain point in their own career, Sanger personally worked with his hands at the bench every single day. Just like Enrico Fermi he did not shun any kind of work, no matter how creative or mundane. In addition he eschewed honors, turning down a knighthood for fear that it might interfere with his work.

It helped that he worked at the best molecular biology laboratory in the world – the MRC Laboratory of Molecular Biology which has produced eight Nobel Laureates. A future Nobel Laureate had vivid memories of Sanger when he was a postdoc at the institute. The postdoc once dropped a large flask of a chemical liquid; as he panicked and looked around for personnel who might clean up the spill, he was startled to come back and see Sanger gently wiping it up with a washcloth. Sanger may have been reserved in the extreme, but he was also extremely helpful and friendly to the brilliant young people populating the institute. Cycling to work every morning come rain or shine, he inspired them through his actions rather than words. The Sanger Institute which was named after him became a pioneer in gene sequencing and contributed to the early draft of the human genome; the institute’s title was a tribute to the man who had made it possible rather any invitation to administrative duties on his part.

Curiously enough, his rules about retirement were as well-defined as his rules about research. After wrapping up his last experiment on the day that he was supposed to retire, Sanger did not again work in the lab and spent the rest of his life gardening. Diligently working at the bench every day of his career, winning two Nobel Prizes, revolutionizing molecular biology and genomics in the process and lovingly looking after his roses; for Fred Sanger it was all in a day’s work. It is now time for us to follow his example, to do more and to talk less.

Ashutosh Jogalekar About the Author: Ashutosh (Ash) Jogalekar is a chemist interested in the history and philosophy of science. He considers science to be a seamless and all-encompassing part of the human experience. Follow on Twitter @curiouswavefn.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. M Tucker 2:17 pm 11/20/2013

    Sanger was a titan of science. He was modest. He was a brilliant scientist and a wonderful human being but I think it best to not attempt to make him into some kind of saint. Because he decline a knighthood that means he “eschewed honors?” I think it just means he was not comfortable with that particular honor. Maybe he did not want to be called sir.

    He did allow an institute for gene research to be named after him. He was happy to personally preside over the opening of that institute. The Wellcome Trust Sanger Institute in Hinxton, England is a world leader in genetic research, was an important leader in the Human Genome Project and continues today with research into “the role of genetics in health and disease.”

    I think it a mistake to criticize the public for not knowing who Sanger is. How is the public to be informed? If science writers are more impressed with theoreticians than experimentalists can we really blame the public for their lack of knowledge. It would be nice to see an actual poll of the general public to see if they could even recognize Witten who was touted in a recent article as the greatest scientist ever.

    We DO need a special award along the lines of the Fundamental Physics Prize to recognize experimentalists. We do need more science writers bringing awareness to experimentalists and their work. The truth of their work and achievements enrich and advance science. Scientists like Sanger do not need artificial aggrandizement.

    Awards and recognitions Sanger did not eschew:

    Fellow of the Royal Society – 1954
    Commander of the Order of the British Empire (King George V) – 1963
    Order of the Companions of Honour (founded by King George V) – 1981
    Order of Merit (Commonwealth, established by King Edward VII) – 1986
    Corresponding Fellow of the Australian Academy of Science – 1982
    William Bate Hardy Prize – 1976
    Nobel Prize in Chemistry – 1958, 1980
    Corday–Morgan Medal – 1951
    Royal Medal – 1969
    Gairdner Foundation International Award – 1971
    Copley Medal – 1977
    G.W. Wheland Award – 1978
    Louisa Gross Horwitz Prize of Columbia University – 1979
    Albert Lasker Award for Basic Medical Research – 1979
    Association of Biomolecular Resource Facilities Award – 1994

    Link to this
  2. 2. M Tucker 5:21 pm 11/20/2013

    Science needs talkers. Science needs showmen and show women.

    Just look at the Royal Institution. Founded in 1799 by a group of British scientists at the home of the then President of the Royal Society Joseph Banks. In 1801 Banks and a few others selected Humphrey Davy as a researcher and lecturer for the institution. Davy was a sensation as a lecturer and attracted a great deal of public attention. The lectures were open to the public. In 1812 Michael Faraday attended one of Davy’s lectures and soon Faraday was working with Davy. Eventually Faraday created two series of lectures for the Royal Institution. The highly formal one hour Friday Evening Discourses and the Christmas Lectures for young people. These are the lectures that continue to this day. Faraday was even more popular than Davy and, in his 73rd year, he was offered the Presidency of the Royal Institution. Faraday humbly declined explaining that he was not the master of the institution but its servant.

    Faraday, humble yet a vocal showman.

    Wouldn’t it be wonderful if the US had a tradition of scientific lectures like this?

    One of the founding members of the Royal Institution was an American but he was a loyalist so he had to leave the country of his birth and take up residence in England, Sir Benjamin Thompson, Count Rumford.

    Link to this

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