Alan R. Battersby

Sir Alan Rushton Battersby (4 March 1925 – 10 February 2018) was an English organic chemist best known for his work to define the chemical intermediates in the biosynthetic pathway to vitamin B12 and the reaction mechanisms of the enzymes involved.

His research group was also notable for its synthesis of radiolabelled precursors to study alkaloid biosynthesis and the stereochemistry of enzymic reactions.

Alan Battersby was born in Leigh, Lancashire, on 4 March 1925, one of three children of William Battersby, a master plumber, and his wife Hilda née Rushton.

At the age of 11 he entered Leigh Grammar School, where his chemistry teacher, Mr Evans, nurtured and encouraged him.

He would have continued his schooling into the sixth form but for the fact that by age sixteen the Second World War was underway and he decided that he should join the war effort by working for BICC in their local factory.

He soon concluded that this decision had been a mistake and so used his spare time to study independently at Salford Technical College for the Higher School Certificate that would be required to enter university.

In 1937, Sonderhoff and Thomas showed how deuterium-labelled acetate could be used to investigate the biosynthesis of fats and steroids; by 1950 13C and 14C labelled acetate had been incorporated into cholesterol.

Battersby realised that these techniques could be used to study alkaloid biosynthesis and that it was timely to do so because simple one-carbon precursors had become commercially available.

By using radiolabelled starting materials incorporating tritium or, especially, 14C to follow intermediates on the pathway, he determined the sequence in which the multiple alkaloids found together in a given organism were formed.

For example, the biosynthesis of morphine was shown to proceed from L-tyrosine via reticuline, salutaridine, thebaine, codeinone and codeine.

The Battersby group worked on many other alkaloids, for example colchicine, (from the autumn crocus Colchicum autumnale) which is used to treat gout.

This was shown to be derived from the amino acids phenylalanine and tyrosine via (S)-autumnaline.

Similarly, the biosynthesis of the indole alkaloids ajmalicine, corynantheal, catharanthine and vindoline was shown to involve the precursors tryptamine and loganin.

In October 1943, Battersby took up his place at the University of Manchester's Chemistry Department, having won a scholarship to support his undergraduate studies.

He graduated with first class honours in 1946 and that year obtained a Mercer Chemistry Research Scholarship (named in honour of John Mercer) and a DSIR grant.

These awards allowed him to complete an MSc (Manchester) in 1947 under the supervision of Dr Hal T Openshaw.

When Openshaw was appointed as a Reader at the University of St Andrews, they both moved there and Battersby completed his PhD, which was awarded in 1949.

He was immediately appointed an assistant lecturer at St Andrews.

This first appointment extended from 1949 to 1953 but was interrupted by two years owing to a Commonwealth Fund Fellowship he obtained for post-doctoral study in the United States.

The first year was spent with Lyman C. Craig at the Rockefeller Institute for Medical Research, New York, working on the peptide antibiotics tyrocidine and gramicidin S.

The second year involved a move to the biochemistry department of the University of Illinois, working with Herbert Carter on pyruvate oxidation factor.

Prior to the 1950s, experimentation, often involving chemical degradation and partial or complete synthesis of possible structures, was necessary to determine their chemical identity which, owing to their stereochemistry, was often difficult to fully describe.

This, for example, was the case for emetine, used for the treatment of amoebic infections and the subject of Battersby's PhD thesis.

As he later commented "'Roughly 100 g of emetine had been consumed in this work; modern tools would allow the structure of emetine to be determined in three days at most using about 10 mg of recoverable material (365 times faster using 10,000 times less material).'"

These tools are the now-familiar mass spectrometry, multi-atom nuclear magnetic resonance spectroscopy and X-ray crystallography: when applied to alkaloids these allowed relationships in structural sub-types to be clarified.

This meant that attention could switch to an understanding of the biosynthetic pathways by which these materials are produced in the bacteria, fungi, plants and animals in which they are found.

In 1954, Battersby was appointed a lecturer at the University of Bristol, where he stayed until 1962.

This was the period when his own research group of doctoral and post-doctoral students became established.

In 1962 he was appointed as a professor of chemistry at Liverpool University until, in 1969, he moved to a professorship at the University of Cambridge and became a Fellow of St Catharine's College.

At the time, this was the second Chair of Organic Chemistry at the University, created especially for him; Lord Todd then held the first.

He won numerous awards including the Royal Medal in 1984 and the Copley Medal in 2000.

In 1988, Professor Battersby was elected to the prestigious 1702 Chair of Chemistry in his department and held that post until his retirement in 1992 when he was granted emeritus status within his college and department, reflecting his distinguished service.

The full output of Battersby's work has been published in over 350, mainly peer-reviewed, articles.

His research, particularly at Cambridge, took a very collaborative approach which was necessary given the extended time period of the ambitious projects undertaken.

Aside from his postgraduate and post-doctoral students, who participated typically for one to three years, the Battersby group included other members of the academic staff of the department, notably Jim Staunton, Ted McDonald and Finian Leeper.

The group was funded by external grants, including those from the SERC, the EPSRC, the Leverhulme Trust, Hoffman-La Roche, the Wolfson Foundation and Zeneca.

Alkaloids are a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms.

They have a wide range of pharmacological activities which has made them of considerable interest to researchers.

He was knighted in the 1992 New Year Honours.

Battersby died in February 2018 at the age of 92.