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Frederick Sanger dies at 95; biochemist revolutionized DNA sequencing

The British researcher was the first person to win two Nobel Prizes in chemistry, and only the fourth ever to win two.

November 20, 2013|Thomas H. Maugh II
  • Frederick Sanger, pictured in 1958 was a biochemist at Cambridge University who twice won the Nobel Prize in chemistry. He died Tuesday at 95.
Frederick Sanger, pictured in 1958 was a biochemist at Cambridge University… (Associated Press )

DNA and proteins are arguably the most important components of the cells of living creatures. Both are produced by stringing together long chains of individual molecules — amino acids in the case of proteins and nucleotides in DNA.

Understanding the identity of the individual molecules in these chains and the sequence in which they are strung together proved to be one of the major biological challenges of the last century. Only by unlocking these sequences would scientists be able not only to understand the fundamental workings of biochemistry, but also to duplicate it.

In the early 1950s, British biochemist Frederick Sanger of Cambridge University developed the first viable technique for determining the amino acid sequence of proteins and used it to describe the structure of insulin, which is composed of 51 amino acids. His work led to the first precise identification of the composition and structure of a protein and proved that such structures are unique.

In honor of that work, Sanger received the 1958 Nobel Prize in Chemistry.

After a move to the Medical Research Council Laboratory of Molecular Biology, Sanger turned his attention to the much more difficult problem of sequencing DNA. By 1977, he and his colleagues were able to establish the sequence of the 5,386 nucleotides in the virus phiX174.

Using a refinement of this technique, in 1981 they established the sequence of human mitochondrial DNA, which is composed of 16,569 pairs of nucleotides — the first human DNA ever sequenced. The following year, they published the sequence of bacteriophage lambda, which has 48,502 base pairs. The technology they used has subsequently been automated and used in sequencing the 3 billion base pairs of the human genome.

For developing this DNA sequencing method, Sanger shared the 1980 Nobel Prize in Chemistry, making him the first person to win two chemistry Nobels, the first Briton to win two Nobels, and only the fourth researcher ever to win two.

Sanger died Tuesday at Addenbrooke's Hospital in Cambridge, near his home in the nearby village of Swaffham Bulbeck. He was 95.

In a statement announcing Sanger's death, Jeremy Farrar, director of the Wellcome Trust, which funded much of Sanger's work, said, "Fred can fairly be called the father of the genomic era: His work laid the foundations of humanity's ability to read and understand the genetic code, which has revolutionized biology and is today contributing to transformative improvements in healthcare."

In a separate statement, Venki Ramakrishnan, deputy director of the Laboratory of Molecular Biology, said that "Fred is one of the outstanding scientists of the last century, and it is simply impossible to overestimate the impact he has had on modern genetics and molecular biology."

Frederick Sanger was born Aug. 13, 1918, in Rendcomb, Gloucestershire, England. His father was a physician and his mother was the heiress of a prosperous cotton manufacturer, which allowed young Sanger to be financially independent through most of his collegiate studies.

He enrolled in St. John's College at Cambridge, intending to follow in his father's footsteps as a physician. He later wrote that he was "not academically brilliant," and that only his parents' wealth allowed him to attend Cambridge. But once he discovered the sciences and, in particular, laboratory experimentation, he found that he could "hold my own even with the most academically outstanding."

He received his bachelor's degree in natural sciences in 1939, just as the war in Europe was beginning. His Quaker religion made him a conscientious objector and he was excused from service and allowed to continue his doctoral research, receiving his degree in 1943.

Continuing to work at Cambridge, he began to explore ways to determine the structure of proteins. Proteins were too large for researchers to simply determine their sequence in a straightforward manner. Working with insulin, which was one of the few proteins then available in a pure form, Sanger developed the idea of breaking it down into smaller peptides, which could be separated and analyzed individually.

A key to this process was Sanger's discovery of a chemical called dinitrophenol, or DNP, which bound strongly to only one end of a protein or peptide chain. Using this reagent, Sanger could analyze each peptide one amino acid at a time, working from one end.

When the original protein was broken apart under varying conditions, the technique produced peptides of different lengths. Overlaps in sequences in peptides produced under different conditions allowed the complete protein to be reassembled much like a jigsaw puzzle.

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