Technology & Medicine › Digital age › Genetic engineering (recombinant DNA)
DNA sequencing
1977 (Sanger; Maxam and Gilbert)· Invention or discovery· Germs, drugs & genetics
Well documentedSolid records, physical evidence or scientific consensus.
Methods for reading the exact order of the four chemical letters, A, C, G and T, in a stretch of DNA.
See it on the Technology & Medicine map →How it works
In 1977 Frederick Sanger in Cambridge, England, and Allan Maxam and Walter Gilbert at Harvard published separate methods. Sanger's copied DNA using some altered letters that stop the copying at random points, producing fragments of every length; sorting them by size spelled out the sequence. His team read the first complete DNA genome, a virus with 5,386 letters. Automated machines with coloured dyes followed in the late 1980s, and much faster 'next-generation' methods after 2005.
Why it mattered
Reading DNA underpins genetic testing, cancer diagnosis, forensics, ancestry tests and virus tracking; a human genome's cost fell from about $100 million in 2001 to under $1,000.
How we know
The 1977 papers by Sanger and by Maxam and Gilbert, Sanger's second Nobel Prize in 1980 (shared with Gilbert and Paul Berg), and US genome-institute cost data.
Still unknown or debated
Reading has outpaced understanding: most genetic differences found in a person's genome still have unknown effects on health.
Connections (3)
▸DNA double helix made possible DNA sequencingWell documented
The connection
Because each DNA letter pairs with only one partner, A with T and C with G, one strand can serve as a template for building a copy. Sanger's 1977 method exploits exactly that: it copies DNA using letters that stop the copying at random points, then reads the sequence from the fragments' lengths.
When and how
Cambridge, England, both times: Watson and Crick at the Cavendish Laboratory in 1953; Sanger at the nearby Laboratory of Molecular Biology, where Crick also worked, in 1977.
How we know
Sanger's 1977 paper relies directly on the base-pairing rule set out by Watson and Crick.
Debates and open questions
Not disputed. A historical puzzle: Sanger read proteins and RNA first; DNA, the obvious target after 1953, took 24 years because its strands are long and chemically uniform.
▸DNA sequencing made possible the Human Genome ProjectWell documented
The connection
Frederick Sanger's 1977 method reads DNA by making copies that stop at each letter and sorting them by length. Automated machines using colored dyes, from 1986, and later capillary sequencers made it fast enough to attempt all 3 billion letters. The project in turn pushed sequencing to industrial scale, cutting costs further.
When and how
Sanger in Cambridge, England, 1977; Leroy Hood's automated sequencer at Caltech, 1986; sequencing centers in the US, UK, Japan, France, Germany and China, 1990–2003.
How we know
The project's papers describe Sanger-type sequencing on hundreds of automated machines; Sanger won his second Nobel Prize for the method in 1980.
Debates and open questions
Whether Celera's faster private 'shotgun' approach would have succeeded without the public project's maps and data is still argued.
▸DNA sequencing decoded, within days, the virus targeted by mRNA vaccinesWell documented
The connection
On January 10–11, 2020, Chinese scientists led by Zhang Yongzhen posted the new coronavirus's genetic sequence online. Because an mRNA vaccine is written in genetic code, Moderna had a vaccine design within about two days, and BioNTech began work within weeks. The vaccines were authorized in December 2020.
When and how
Shanghai, January 2020, with the sequence posted via Edward Holmes in Sydney; vaccine designs at Moderna in Cambridge, Massachusetts, and BioNTech in Mainz, Germany.
How we know
The posted sequence is time-stamped in public databases; Moderna and NIH records document design dates, and the first trial doses were given on March 16, 2020.
Debates and open questions
Not disputed. An open question is how fast the next vaccine can come: global planners now aim for 100 days from sequence to approved vaccine.