Obituary for Dr Cliff Elcombe
Dr Cliff Elcombe was a well-known and accomplished British toxicologist, who spent almost his entire career investigating the mechanisms of toxicity of various industrial chemicals and agrochemicals. He had an enviable reputation for his knowledge of, and insight into, non-genotoxic mechanisms of carcinogenesis and was internationally recognized for his work in predicting whether adverse effects of chemicals seen in experimental animals were likely to be replicated in the human population. The development of the role of mechanisms of toxicity in human risk assessment analysis has greatly enhanced the science of toxicology from that of an observational science into a more rational predictive science. Cliff Elcombe was one of the leading exponents of this philosophy, which helps to avoid exaggerated concerns of toxicity of chemicals as well as establishing the identity of those compounds to which humans should not be exposed.
Clifford Roy Elcombe was born on 24th October 1950 in Dartford, Kent. He attended Dartford Grammar School (1960-1969) and then completed his BSc in Biochemistry at the University of Surrey. He remained at Surrey to complete his PhD in the laboratory of Jim Bridges and completed his thesis on the hepatic microsomal metabolism of methylenedioxyphenyl compounds. During his PhD, Cliff worked as a Royal Society Research Fellow in the laboratory of Karl Netter (University of Mainz) and collaborated with Roland Wolf on his first publication (in Xenobiotica). On completion of his PhD, Cliff moved to the College of Medicine, University of Wisconsin, where he worked with Dr John Lech on the metabolism of polybrominated biphenyls in rainbow trout (Salmo gairdneri). He and John Lech subsequently described the induction of cytochromes P450 in the rainbow trout. Cliff’s PhD and his first postdoctoral period in Wisconsin were highly productive and he was asked to lead a work group in the relatively newly-formed Biochemical Toxicology section led by Mike Rose in the Central Toxicology Laboratory (CTL) of ICI Ltd. It was in this laboratory that, during the next twenty years or so, Cliff, along with his colleagues Martin Ellis, Trevor Green, Ted Lock, Marsh Middleton, Mac Proven and Lewis Smith, established an international reputation for studying the mechanisms of toxicity of various classes of chemicals. Cliff and his colleagues determined and published the metabolism of various xenobiotics of interest to ICI Ltd., and he was amongst the first in the field to recognize the importance of chemically-induced non-genotoxic carcinogenesis. More importantly, Cliff recognized that the species differences in the response of experimental animals to treatment with the same xenobiotic, meant that the challenge was to establish how human tissue responded since this would have significant implications for the registration and use of those chemicals that produced cancer in experimental animals.
Cliff recognized early in his studies of xenobiotic mechanisms of toxicity, the role of peroxisome proliferation in the differing carcinogenic outcomes seen in various species of experimental animal. During the 1980’s and 1990’s Cliff and his colleagues worked on the metabolism, induction of peroxisomes and carcinogenicity of several chemicals of scientific interest and/or industrial importance. The conclusions from these studies provided a basis for the identification and characterization of PPAR α by Stephen Green (at CTL) and the subsequent study by scientists throughout the world on the various forms of PPAR and their role in human disease. Cliff investigated the species specificity of trichloroethylene in causing liver cancer in and this work led to the award of ‘Young Scientist of the Year’ in 1984, by the European Society of Toxicology.
In 1997 Cliff decided to move to the University of Dundee where he was reunited with Roland Wolf, who was now responsible for a successful research program within the University. It was with Roland that Cliff co-founded CXR Biosciences Ltd. in 2001 in laboratories within the University complex. Through this organization, Roland and Cliff maintained an active research program on the relevance of the metabolism of xenobiotics and the implication of this for their carcinogenic potential. CXR continued to work for various industrial organizations, including CTL as well as with other companies with an interest in mechanisms of toxicity. CXR developed an enviable reputation as a scientific resource for solving industrial toxicological problems. In 2012, Roland Wolf separated from CXR to focus on his University research group. In the reorganization that followed, Cliff played a major role in the continuing evolution of CXR into a mature and successful company, as well as in building and developing a highly skilled team of toxicologists and laboratory scientists at its Dundee base. This process culminated in CXR, by now a company of around 40 employees based in its own dedicated facilities with an international client base, being acquired by Concept Life Sciences in August 2015.
Concept Life Sciences acquired CXR as part of the formation of a larger and more broadly based CRO to service science-based companies in the pharmaceutical, agro-science and industrial sector. Cliff retained his long-standing position as Research Director and was excited and engaged in how CXR could maximize its contribution to the new organization.
There is no doubt that Cliff Elcombe, the scientist, made a significant contribution to our understanding of the mechanisms of non-genotoxic carcinogenesis. He had an enormous intellect for scientific issues. Those of us who worked closely with him, would observe him casually and almost absent-mindedly reading Nature or other scientific journals. On several occasions he would be asked ‘what’s new’ and his almost frightening detailed description of what was in the latest journal would be given. It almost seemed as if he learned by osmosis because he did not have to study the paper to establish the essence of its ‘message’.
During his career, Cliff has supervised tens of PhD students, some directly, and others he co-supervised. He was always interested to know what they had discovered and what they thought they had achieved. He could be critical and didn’t like any kind of ‘waffle’ or his more vernacular term for it. His post-docs benefitted from working with him and he was conscientious in ensuring that the best found good research opportunities, and the others employment.
No acknowledgement of the humanity of Cliff would be complete without acknowledging two striking characteristics:
First, Cliff loved to socialize with his workmates and scientific colleagues. As a younger man he could burn the candle at both ends … and then some. He was open and generous, critical and instructive, almost at the same time. He had a terrific sense of humour and was able to take as well as give. He was knowledgeable about cricket and had played for the county of Kent’s under 21s and then with local teams depending on his location.
He was knowledgeable about wine, cheese, cooking (which was his form of practical chemistry) and was always an interesting companion. Some could see no further than this terrifically social, and sometimes dominating presence. For those who worked with him there was a deep respect for what he knew and for his opinions, a kind of almost annoying acceptance that, even if he was not entirely right, he was very close to the solution of where the problem lay, and if you were going to argue with him, you needed to be well-prepared.
Second, Cliff was fiercely loyal: to his wife, children, those who worked for him and his friends. It was a brave person who tried to criticize any of the aforementioned. His love for his family was evident when he talked of them. Cliff only wanted the best for them and was a proud, inspirational father who was at his most benign and gentle when telling how they were. His death came tragically only a week before one of his sons was due to marry. He was so looking forward to the wedding.
Toxicology may be poorer today for the loss of Cliff, but it is richer for his contribution to the role of mechanisms in human risk assessment. For those who worked with, or knew Cliff, we are richer for having known the man, and it can only be our hope that he knew how much he will be missed.
Lewis Smith
