The Man Who Mapped Life's Chemistry: Frederick Sanger and the Story of Genetic Sequencing

Anyone who has read about genetics will have heard his name. The British biochemist and two-time Nobel Prize in Chemistry recipient Frederick Sanger was known for his modest personality throughout his life. Born in England on 13 August 1918, he studied natural sciences at the University of Cambridge. He was exempt from military service during the Second World War and continued his scientific research during that period. 

Sanger received the Nobel Prize in Chemistry in 1958 for determining insulin's structure and in 1980 for his contributions to identifying base sequences in nucleic acids, becoming the only scientist to win twice in the same category. He died in 2013 at the age of 95. The genetic sequencing technique bearing his name remains in use. Developed in 1977, it plays an important role in providing genetic data for applications such as confirming PCR results, phylogenetic analysis, epidemiological studies, and forensic investigations.

“The man who mapped life's chemistry” was how he was described.

Next-generation sequencing (NGS) technologies are comparatively faster, but Sanger sequencing remains a preferred technique in many studies because of its flexible applications and high accuracy.

The Sanger Method

Frederick Sanger studied DNA structure in particular to develop his sequencing method. In 1977, he introduced the “dideoxy,” or “chain-termination,” method for determining DNA sequences. The technique was designed to sequence short DNA fragments by terminating the chain during copying. It uses DNA polymerase, the four types of bases (adenine, thymine, cytosine, and guanine), and a dideoxy version of each base. Dideoxy bases stop a chain from growing, producing DNA fragments of different lengths. These are separated by electrophoresis so that their sequence can be read. The technology was later used in the Human Genome Project and many other genomic studies.

The process of determining a DNA sequence by the Sanger method can be summarized in 7 steps:

1. A double-stranded DNA (dsDNA) fragment is separated into two single-stranded DNA (ssDNA) fragments.
2. The ssDNA fragment is amplified into millions of copies.
3. A primer complementary to one end of the fragment is added.
4. Fragments are added to four polymerase solutions. Each contains all four types of bases, but only one type of terminating nucleotide.
5. The chain continues growing until a terminating nucleotide is randomly incorporated.
6. The resulting double-stranded DNA fragments are separated to produce a series of single-stranded fragments of different lengths.
7. Fragments are separated by electrophoresis and the sequence is read.

In addition to this outline, each terminating nucleotide used in the method is usually marked with a different fluorescent label. A laser detector reads these labels after electrophoresis, identifying the sequence in an automated DNA sequencing instrument.

Earlier Work: How Did Sanger Sequence Insulin?

To determine insulin's amino acid sequence, Frederick Sanger developed new methods for breaking proteins into fragments and identifying their amino acids in order. In particular, he used chemical methods to divide proteins into smaller pieces and identify amino acids at their ends. By fragmenting insulin and analyzing each fragment's chemical structure, he reconstructed their order and thus insulin's complete amino acid sequence. This work earned him the Nobel Prize in Chemistry in 1958 and laid the foundation for protein sequencing. It also paved the way for the subsequent development of DNA sequencing techniques.

From the Nobel Prize to the Garden: Frederick Sanger's Humble Journey

In 1992, the Wellcome Trust and Medical Research Council established the Sanger Centre in Hinxton, near Sanger's home. In allowing his name to be used, he politely warned John Sulston that their work would have to be excellent. Sanger declined a knighthood because he did not want to be called “Sir,” accepting the Order of Merit instead.

Known for his modesty in science, Sanger also humbly accepted support for archiving and preserving the 35 laboratory notebooks recording his research. In retirement, he gardened at his Cambridgeshire home, displaying qualities that reflected the depth of his character as well as his scientific contributions.

A scientific genius throughout his academic life and an inspiration to students and colleagues, Sanger argued that understanding and developing basic science mattered greatly alongside practical research applications. His life story weaves together scientific curiosity, dedication, and humility. His work pioneered fundamental techniques still used in genetics and molecular biology.

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