More than a century ago, the German pathologist Alois Alzheimer observed that people who died with dementia had deposits of an insoluble material in their brains, later known as amyloid plaques. Amyloid turned out to be made of protein, but in a form unlike the thousands of proteins our cells turn out every minute of our lives to carry out all our essential functions.
Chris Dobson, who has died aged 69 of pancreatic cancer, devoted his life to explaining the chemical processes that disrupt the production of healthy proteins and instead trigger their aggregation into toxic clumps. He focused on the mechanisms that direct long protein chains to fold up into the three-dimensional shapes that allow them to engage in essential biochemical interactions, and exhaustively researched the question of how they “misfold” when these mechanisms fail, instead adopting forms that stick tightly to one another as toxic amyloid fibrils.
Dobson pursued the question out of scientific interest, but came to realise that his discoveries were of enormous potential benefit to patients: the range of misfolding diseases now includes diabetes and Parkinson’s disease as well as Alzheimer’s, and many others that are less well known. He was knighted in 2018 for his work, among a host of international awards.
A key discovery came about by chance. In the early 1990s one of Dobson’s graduate students left a solution of the protein lysozyme (derived from egg white) inside a laboratory instrument over the weekend, and found on his return that it had set like a jelly. On closer inspection it proved to contain amyloid fibrils, structures that until that moment Dobson had known only from descriptions of disease.
Using the latest advances in nuclear magnetic resonance spectroscopy and mass spectrometry, techniques that had only recently begun to be applied to molecules as large as proteins, Dobson and his colleagues systematically set about understanding the dynamics of protein folding and misfolding, applying insights from chemistry to this biological problem.
He went on to provide a strong theoretical underpinning by writing a mathematical description of the way fibrils form, and of how they can set off a chain reaction by “seeding” the production of new fibrils, as happens in prion diseases such as bovine spongiform encephalopathy.
More recently he turned to drug discovery, screening a variety of agents for their ability to prevent fibrils forming. Encouraging laboratory results suggest this approach could transform the prevention and treatment of the diseases of ageing, which emerge as the body’s natural repair mechanisms begin to fail.
Born in Rinteln, in Lower Saxony, Germany, Dobson’s roots were in Yorkshire. His parents, Arthur and Mabel (nee Pollard), grew up in Bradford, and both left school without qualifications. Arthur worked in the wool exchange before joining the army on the outbreak of war. He rose through the ranks and had been commissioned as an officer by the time Chris was born, the third of three children after his siblings, Graham and Gillian. The family followed their father from one posting to another, including a spell in Nigeria. Dobson’s education became more stable when he went to the Cathedral preparatory school for boys in Hereford and then to Abingdon school in Oxfordshire, where he enjoyed excellent science teaching.
He entered Keble College, Oxford, to read chemistry in 1967, graduated with a first, and then moved to Merton College, Oxford, for a doctorate. As a graduate student with the physicist Iain Campbell, he was one of the first to demonstrate dynamic change in the structure of a protein molecule (lysozyme) using nuclear magnetic resonance.
After a spell at Harvard University he returned to Oxford as a lecturer in chemistry and fellow of Lady Margaret Hall in 1980, and subsequently became founding director of the Oxford Centre for Molecular Sciences.
Dobson moved to Cambridge University in 2001 as John Humphrey Plummer professor of chemical and structural biology. Thereafter his research group began to apply their new understanding of protein folding more directly to diseases such as Alzheimer’s and Parkinson’s, and in 2012 he founded the Cambridge Centre for Misfolding Diseases. In 2016 he completed the journey from basic science to medical application when he co-founded Wren Therapeutics, a company specialising in drug discovery and development for such diseases.
He always insisted his discoveries owed everything to the bright young people he attracted to work with him, and paid particular attention to promoting the careers of women in his lab – for example he appointed Carol Robinson, now president of the Royal Society of Chemistry, to a post-doctoral position at Oxford after she had taken an eight-year career break to raise her family.
In 2007 Dobson accepted the post of master of St John’s College, Cambridge. He threw himself into the life of the college and was reputed to know the name of every student and staff member. He took particular interest in making St John’s more accessible to students from non-traditional backgrounds, introducing a grant scheme for those from low-income families and initiatives for students with disabilities.
In 1977 he married Mary Schove, a historian of medicine. She survives him, as do their sons, Richard and William.
• Christopher Martin Dobson, chemist, born 8 October 1949; died 8 September 2019
