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Alan Battersby Obituary

We are grateful to Ted McDonald and Finian Leeper, former colleagues of Alan, for the following obituary.

Professor Sir Alan Battersby FRS died peacefully in Cambridge on 10th February, aged 92, following a short illness. Alan was one of the most eminent organic chemists of his generation and is renowned for deciphering the routes by which complex natural products are built in nature from basic chemical building blocks, such as amino acids and sugars.

Always known as ARB or 'Prof' to members of his research group, Alan was a great leader who inspired hard effort and loyalty by his own example and by his energy and enthusiasm.  The experience of working in the Battersby group provided a solid platform for launching the careers of more than 100 chemists, many of whom went on to make significant contributions in academia and industry.

His research output began in 1948 at the University of St Andrews where he was a PhD student under the supervision of Prof Harry Openshawe.  His research project culminated in the laboratory total synthesis of emetine, a complex alkaloid that is the active ingredient of tincture of ipecacuanha.  This was a significant achievement for a single chemist using the technical tools of the day, and it later became normal for similar projects to require team efforts.  In 1951-2 Alan held Fellowships at Rockefeller University and at the University of Illinois, where he gained valuable experience in new techniques (eg. chromatography) for the separation of complex mixtures derived from plant extracts.

He will be greatly missed by all who had the privilege of knowing him, but his scientific achievements will endure for as long as we remain curious about the chemistry of nature’s products.

In his next post as Lecturer at University of Bristol (1954-62), he set forth on a quest to study the biosynthesis of natural products, starting with the morphine alkaloids produced by the poppy family.  Earlier generations of chemists, notably Sir Robert Robinson, had speculated that such alkaloids might derive from amino acid building blocks via a sequence of multiple transformations but there had been no possibility of testing these ideas experimentally.  Around 1960 simple radioactive isotopes such as 14C (a radioactive isotope of carbon), became commercially available for the first time and Alan realised that these could be used to study biosynthetic pathways in plants.  For example, radioactive formaldehyde, CH2O, would be used in the laboratory to prepare a sample of an amino acid (9-12 carbon atoms) labelled with 14C at a specific site.  This chemical would be injected into the seed-head of a poppy and, after a week or so, pure morphine would be isolated from the plant and tested for radioactivity.  To clinch the result, the labelled morphine sample would be degraded to test whether the radioactivity was confined to the single expected site.  In this way the biosynthetic pathway to the morphine alkaloids was mapped out rigorously and in detail by both the Battersby group and that of Sir Derek Barton.

In 1962, Alan was appointed to a Research Chair of Chemistry at the University of Liverpool.  Here he built a substantial team of around a dozen PhD students and postdoctoral coworkers, and invited junior colleagues Jim Staunton and Bob Ramage to collaborate and assist with running his group, alongside their own research interests.  With their help, Alan continued his quest to map the pathways leading to many complex alkaloids (including colchicine, used to treat gout, and the complex indole alkaloids, used in chemotherapy for cancer) in a diverse range of plants, with the outcome that it became possible to classify the majority of newly discovered alkaloids according to their likely derivation.  Fascinating new biosynthetic reactions and their mechanisms  were revealed in these researches, as well as intricate details of the stereochemistry of the enzyme controlled reactions.  Professors Ian Scott and Duilio Arigoni were academic competitors on some of these projects but the three interacted amicably and on occasions published their results back to back in a  Journal of the Royal Society of Chemistry.  In recognition of his work, Alan was elected a Fellow of the Royal Society in 1966.

In 1969 Alan accepted an appointment to a Chair of Chemistry at University of Cambridge where he stayed for the remainder of his career.  Jim Staunton moved with him and Ted McDonald, formerly a PhD student of Alan’s, now joined him as a co-director.  Alan clearly felt that this was an opportunity, with an expanded research team, to tackle a different and potentially more important set of problems.  He therefore began work on the tetrapyrrole pigments, a class of natural products that include the oxygen-binding site of haemoglobin; the chlorophylls; and vitamin B12.  In the event, this project could not be solved by existing methods and Alan (with McDonald) became a pioneer in the use of multiple 13C labelling for studying molecular rearrangements; and later, with collaborators Chris Abell and Finian Leeper, of importing genetic approaches to solve biosynthetic problems.

 Great progress had been made on the tetrapyrrole project by the due date for Sir Alan’s retirement in 1992 but a little more effort was needed to complete the definition of the pathway to structurally-complex vitamin B12.  Fortunately Sir Alan was granted an extension of his research funding, supported by his departmental colleagues, and was able to complete the project at age 70 in 1995.  Vitamin B12 had for decades fascinated organic chemists for its complexity.  Structure determination was a major project for Lord Alexander Todd and was ultimately solved by the pioneering X-ray crystallography of Dorothy Hodgkin.  The total synthesis of vitamin B12 was the crowning achievement of a decade-long collaboration between teams led by Professors Albert Eschenmoser (ETH Zurich) and R B Woodward (Harvard). And now the Battersby group, in collaboration with scientists from the French pharmaceutical company Rhône-Poulenc (now part of Sanofi), had finished mapping out every step in the lengthy biosynthetic route to this important vitamin.

Alan’s achievements were recognised by many awards from worldwide professional bodies including Paul Karrer Medal, University of Zürich (1977); Davy Medal (1977); Roger Adams Award (1982); Royal Medal (1984) and the prestigious Copley Medal (2000) both by the Royal Society; Havinga Medal, Holland (1984); the Feltrinelli International Prize for Chemistry, Italy (1986); Robert Robinson Medal by the Royal Society of Chemistry (1986); Adolf Windaus Medal, Göttingen (1987); Wolf Prize in Chemistry (1989) and in 1992 he was knighted.

Always known as ARB or “Prof” to members of his research group, Alan was a great leader who inspired hard effort and loyalty by his own example and by his energy and enthusiasm.  The experience of working in the Battersby group provided a solid platform for launching the careers of more than 100 chemists, many of whom went on to make significant contributions in academia and industry.  His manner was always warm and friendly and he was the perfect gentleman, but he was also single minded and did not encourage idle social chatter.  It was therefore a big surprise to his co-directors when he revealed to us, around 2015, how his career had almost been derailed before it began.  Alan was a bright pupil who completed his School Certificate (the equivalent of O-levels) at Leigh Grammar School in 1941 and was destined for the sixth form.  But, inspired by Churchill’s speeches on radio he left school to join a local cables factory, British Insulated Callender's Cables, to assist the war effort, against the advice of his teachers.  Soon he became aware that he would need a university degree to achieve his scientific and career goals, and he studied alone, nightly after work, for the next 2-3 years until he passed the Higher School Certificate.  A university course would have been unaffordable without a scholarship but with great good fortune he was just in time to sit a qualifying examination and was then able to study chemistry at Manchester University, graduating with First Class honours after just two years and three months.  Thereafter he made his way safely up the academic ladder.  His work is highly regarded worldwide, and he made many friends during lecturing trips overseas especially in Switzerland, USA and Japan.  He was a highly respected consultant for several bioscience companies including Roche, ICI (now Astra Zeneca and Syngenta) and Fisons (subsequently FBC and Schering). 

Alan always worked hard but was also devoted to his family.  His wife Margaret was a botanist and she played a part in helping him acquire plants for his biosynthetic studies.  Holidays with their two sons were full of adventure, involving camping and (later) dinghy sailing, in the UK and Europe.  In 1977 Alan and Margaret acquired a small cedarwood cottage on the shores of Loch Sunart in Scotland, with no electricity or phone and with water supplied from the local ”burn” (stream).  They loved the tranquillity, isolation and majestic scenery.  Tragically, Margaret died of cancer in 1997 when Alan had barely retired and he clearly felt the loss deeply.  Throughout his time in Cambridge Sir Alan visited his college, St Catharine’s, almost daily and this continued in retirement.  He became a much-loved and respected member of the College Fellowship.  Since Margaret died, he packed-in many hiking holidays around the world, some very physically challenging, and he was a keen fly fisherman.  At the age of ninety he took up painting with water colours, with colleague Brian Johnson as tutor, and produced some impressive pieces.

Alan is survived by two sons, both themselves retired, Stephen (a physicist and R&D leader in the electronics industry) and Martin (a biochemist and agribusiness R&D leader), four grandchildren, and three great-grandchildren.  He will be greatly missed by all who had the privilege of knowing him, but his scientific achievements will endure for as long as we remain curious about the chemistry of nature’s products.