Frederick Sanger: Sequencing Life's Polymers

• The first protein was sequenced, followed by a surge in protein research.
• This surge enabled the development of synthetic insulin for treating diabetes.
• Following receipt of the Nobel Prize in Chemistry in 1958 for work on insulin Sanger had the freedom to pursue his most ambitious research goals.
• In1962, Sanger moved to the Laboratory of Molecular Biology in Cambridge.
• He turned his attention to exploring the structure of genetic nucleic acids, RNA, and DNA, after catching what he called "the sequencing bug".
• Sanger's Cambridge colleagues Francis Crick and James Watson discovered the double-helix structure of DNA in 1953.
• Sanger aimed to untangle this DNA structure to reveal the bases in specific strands, each carrying a distinct genetic code.
• Sanger began with RNA, a smaller and less complex single-stranded nucleic acid.
• According to the information encoded in DNA, Sanger developed a sequencing method using radioactive isotopes to "label" individual fragments.
• Sanger’s method built the sequence by looking at areas of overlap between individual fragments.
• By 1967, Sanger had a complete sequence of RNA from E. coli bacteria.
• In the early 1970s, Sanger moved on to DNA sequencing, which was more difficult due to DNA's size and double-helix structure.
• Sanger’s team pioneered a method of isolating DNA fragments via dideoxy chain-termination in 1977 which uses a molecular inhibitor to prevent DNA strands from extending.
• These strands could then be ordered from shortest to longest, allowing the base sequence to be read.
• This method enabled Sanger to map the first human genome, the DNA of cell mitochondria, in 1981.
• Sanger’s work led to the sequencing of all 3 billion base pairs of the entire human genome.
• Sanger's sequencing method allowed fragments of DNA to be isolated, cloned, and reattached to create modified genes for treating or resisting genetic disorders.

Additional information

• Frederick Sanger quoted in 2001: "I had 20 years when I could just do what I wanted."
• By 1982, 48,502 base pairs of DNA had been sequenced.

John Sulston

• English biologist John Sulston was the first director of the Wellcome Sanger Institute genome research center.
• Sulston shared the 2002 Nobel Prize for work on programmed cell death.
• Sulston's research centered on Caenorhabditis elegans, a 0.03-in (1-mm) nematode worm, from 1942-2018.
• This worm has an exact number of cells, making it ideal for studying cell differentiation, division, and programmed death.
• Sulston pushed for the genetic sequencing of C. elegans, which became the first animal to have its entire genome sequenced in 1988.
• This led directly to the Human Genome Project (1990-2003), in which Sulston was a key contributor.