Research carried out by Professor Chris Marshall to identify the genes that potentially trigger cancer and analyse the signalling faults that cause them to proliferate, paved the way for four new classes of cancer drugs, two of which are now widely used in the treatment of the disease.
Yet in its early stages the research was almost abandoned. Marshall was recruited as a team leader at the Institute of Cancer Research (ICR) in London in 1980 to begin studies to identify human oncogenes, the term for these potential triggers. It had already been established that faulty genes were present in cancerous cells and the ICR had pinpointed the possibility of disrupting these genes as a new avenue for treatment.
Marshall, who had long been fascinated with the behaviour of cells, formed a team with his late colleague Alan Hall, whose expertise was in the study of DNA — deoxyribonucleic acid — which stores genetic information. The two men sought to isolate the genes by transplanting segments of tissue from tumours into healthy cells.
Yet for more than a year, they were unable to identify any specific oncogenes. They agreed to try the technique on 20 more samples before giving up and looking for a new direction in their research. Fortunately, their persistence was rewarded and they found evidence of an oncogene in two of the last batch of samples and were able to show that it was probably the same gene from two different tumours. They named it NRAS.
The publication of their findings in Nature in 1983 was regarded as a landmark in the scientific understanding of the genetic triggers in cancer development. Around 12 per cent of all human cancers contain an oncogenic version of NRAS or of two closely related genes that were identified in the United States at about the same time.
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Marshall continued his research at the Institute for 35 years, making several more important discoveries that have furthered the knowledge of how cancer cells communicate. He was working there until shortly before his death — from liver failure as a result of colorectal cancer — at the age of 66.
Christopher John Marshall was born in Birmingham in 1949, the only child of parents who were both from the northeast of England, where his grandfather had been a coalminer. His father was the works manager at the Massey Ferguson tractor plant. The young Marshall first acquired his interest in science at King Henry VIII School in Coventry and went on to take a degree in natural sciences at Churchill College, Cambridge.
He moved on to Lincoln College, Oxford, where he took a DPhil in cell biology at the Sir William Dunn School of Pathology, which set him on the path to becoming a specialist in cancer research. He joined the Imperial Cancer Research Fund (now Cancer Research UK) to work at its laboratories in Lincoln’s Inn Fields in London, and was later recruited by the Dana-Farber Cancer Institute in Boston in the United States.
However, it was his appointment to the Institute of Cancer Research in London at a time when scientists were beginning to devote much more study to the mutations that are found in tumour cells that gave him the opportunity to work with one of the most renowned teams in the field. Not content with simply discovering the NRAS oncogene, he was determined to understand how it could be triggered to cause the disease. With a rigour that colleagues regarded as his trademark approach, he analysed how certain proteins transmitted signals from the fringe of the cell to the nucleus and how this pathway became disrupted in cancer.
His careful analysis of the complex route by which these signals were transmitted established the role of certain proteins within the cell in malignant tumours and opened the way for the development of drugs that specifically target these proteins. Recently approved drugs of this kind are now being used to benefit patients worldwide. He became professor of cell biology and then director of research for the ICR, developing a strategy that was based on his belief that the findings of cancer research should be translated into treatments as quickly as possible.
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Outside of his work, he took up cycling with an equal passion, joining the Norwood Paragon, a south London road club, where he established a reputation as a fierce and determined racer. Over four seasons from 1987 onwards, he was a member of many victorious teams in time trials ranging from ten-mile sprints to 12-hour marathons, once completing a remarkable 256 miles in the alloted time. He held several club records.
Fellow members of the club had little idea about who the unassuming scientist was until one of the youngsters, who had ridden alongside him in a recent event. took his advice to apply for a course in science. He went for a college interview and mentioned that he had been training with Chris Marshall the previous week. That, said the student, was the end of the interview. “I was in.”
Marshall gave up competitive cycling when he discovered that he had brittle bones, suffering a broken hip and elbow in various crashes, but he continued to ride, training regularly in Richmond Park. He also made long rides around the Mediterranean island of Majorca, where he had a holiday home with his second wife, the former Lesley Ford, who was a charity worker. He told colleagues that he often thought about experiments as he was cycling.
His first marriage to Viviene Morrell, whom he had met at Oxford, ended in divorce. They had three children: Joseph, who is an opinion pollster; Lucy, who is a head teacher at a special needs school; and Francis, who took a science degree and works for Cancer Research UK. A keen, if somewhat chaotic cook, he liked to try out new recipes on his family, which also gave him a chance to exercise his taste for fine wines.
Marshall was elected a Fellow of the Royal Society and the European Academy of Cancer Sciences and was a founding member of the Academy of Medical Sciences. He was awarded the 1999 Novartis Medal of the Biochemical Society, and the 2008 Buchanan Medal of the Royal Society, for his distinguished contribution to medical sciences. He received the Biochemical Society Centenary Award this year.
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Almost to the end, he was still working on the cell signalling mechanisms that promote the spread of cancer. The work will continue in the hands of younger scientists who benefited from his advice as a mentor.
Christopher Marshall, cancer researcher, was born on January 19, 1949. He died of cancer on August 8, 2015, aged 66