Alexander Todd

Alexander Todd: The Chemist Who Built DNA's Backbone

In 1949, in a Cambridge laboratory, Alexander Todd synthesized adenosine triphosphate — ATP, the molecule that carries usable energy inside every living cell. Two years later he established how the backbone of DNA is stitched together, with carbon atoms 3 and 5 of the sugar rings bound through phosphate. When Watson and Crick unveiled the double helix in 1953, Todd's chemistry was the scaffolding it hung on. He had already been, at thirty-one, the youngest professor of chemistry in Britain since Frankland.

A Glasgow Start

Alexander Robertus Todd was born on 2 October 1907 in Cathcart, on the outer edge of Glasgow, the elder son of Alexander Todd, a clerk on the Glasgow Subway, and Jane Lowry. He was educated at Allan Glen's School and then at the University of Glasgow, where he took a BSc in chemistry in 1928.

Then he did what few British chemists of his generation did: he left. At Goethe University Frankfurt he earned a doctorate in 1931 with a thesis on the chemistry of bile acids, absorbing the German tradition of structural organic chemistry at its source. Back in Britain on an 1851 Research Fellowship, he took a second doctorate — a DPhil at Oriel College, Oxford — in 1933. By twenty-six he had been trained twice over, in two of the strongest chemical cultures in the world.

The Fast Ascent

Todd joined the staff of the University of Edinburgh in 1934. In 1937 he married Alison Sarah Dale, daughter of Henry Hallett Dale, a Nobel laureate in his own right; they had three children, Alexander Henry, Helen Jean and Hilary Alison. In 1938 Manchester gave him the Sir Samuel Hall Chair of Chemistry. He was thirty-one — the youngest man to hold a British chair of chemistry since Edward Frankland. That same year he spent six months as a visiting professor at the California Institute of Technology, and turned down the permanent faculty post Caltech offered him. He would build his school in Britain.

In 1944 Cambridge elected him to the 1702 Chair of Chemistry, which he held for twenty-seven years, until his retirement in 1971. There the work that mattered was done.

The Work

Todd chose the least glamorous and most consequential target available: nucleotides, nucleosides and the nucleotide coenzymes — the individual chemical units from which DNA and RNA are assembled, and the molecules through which cells move energy. In the 1940s nobody could make them cleanly, and until you can build a molecule you cannot claim to understand it.

In 1949 his group synthesized adenosine triphosphate and flavin adenine dinucleotide. ATP is the universal energy currency of biology; FAD is a carrier at the heart of cellular respiration. Producing both in the laboratory settled their structures beyond argument and gave biochemistry a supply of pure, defined material to work with.

In 1951 came the structural result. Todd's group showed, by chemical means, how the DNA backbone is linked: carbon 3 of one sugar to carbon 5 of the next, through a phosphate bridge. Two years later Watson and Crick's X-ray-based model of the double helix appeared and was corroborated by that chemistry. A helix is only a shape; Todd supplied the covalent grammar that made the shape possible.

He kept going. In 1955 he helped elucidate the structure of vitamin B12, the most structurally forbidding vitamin known, though it was Dorothy Hodgkin who fixed the final formula by crystallography. He worked on vitamin B1 and vitamin E, on the anthocyanin pigments that colour flowers and fruit, and on the alkaloids of cannabis; in 1940 he became the first person to make H4-CBD and H2-CBD by hydrogenating cannabidiol.

Recognition

The Royal Society elected him a Fellow in 1942. He was knighted in 1954, the year he was also Arthur D. Little Visiting Professor at MIT, having been Nieuwland Lecturer at the University of Notre Dame in 1948. The US National Academy of Sciences took him in 1955 and the American Academy of Arts and Sciences in 1957 — the year the Nobel Prize in Chemistry came to him "for his work on nucleotides and nucleotide co-enzymes." The American Philosophical Society followed in 1965. In 1977 the Queen appointed him to the Order of Merit, the most restricted honour in Britain. More than forty universities gave him honorary degrees.

The Public Chemist

Todd's second career was institutional. From 1952 to 1964 he chaired the British government's advisory committee on scientific policy, the body through which postwar Britain decided what science it would pay for. In 1962 he was made a life peer as Baron Todd of Trumpington. He was Master of Christ's College, Cambridge from 1963 to 1978, the first Chancellor of the University of Strathclyde from 1965, and President of the Royal Society from 1975 to 1980 — a rare sweep of the commanding positions of British science. He was a founding member of the World Cultural Council in 1981 and taught as a visiting professor at Hatfield Polytechnic from 1978 to 1986, past seventy and still lecturing.

Last Years

His wife Alison died in 1987. Todd died in Cambridge on 10 January 1997, aged eighty-nine, following a heart attack. The Royal Society of Chemistry later placed a blue plaque at the Cambridge chemistry department where he had worked.

Why Todd Matters

The molecular biology revolution is usually narrated through physicists and crystallographers. It could not have happened without chemists able to take the molecules of heredity apart and put them back together. Todd was the greatest of them. He made ATP. He defined the linkage that runs the length of every chromosome. And he led a department that supplied the field with both its people and its methods. He got the chemistry of life's information right by building it, one bond at a time.