Abstract
Dr. Francis John Caldwell Roe was for over 50 years active as an experimental pathologist. He had a wide range of research interests, which included the general toxicology and potential carcinogenicity of foods, food additives and contaminants, drugs, tobacco, pollutants and industrial chemicals, as well as mechanisms of carcinogenesis, cancer epidemiology, cancer prevention, and the pathology of laboratory animals. This resulted in over 800 publications, including 8 books and many leading articles in the British Medical Journal and Lancet. His encyclopaedic knowledge, coupled with his ability to present his findings in an extremely clear and logical way, made his advice highly sought after. He served with distinction for many years on the UK DHSS Committees on Carcinogenicity and on Toxicity and on the WHO Expert Advisory Panel on Food Safety. He was also a member of numerous other national and international expert committees as well as of various scientific journal editorial boards, and was a highly valued consultant to a wide range of companies.
He obtained from Oxford his B.A. in 1945, B.M. and B.Ch. in 1948, M.A. in 1950, and D.M. in 1957. He took up a house appointment at the London Hospital in 1948, continuing his pathology experience at the Royal Army Medical College from 1949 to 1951 before returning for 10 years to the London Hospital to be lecturer, then senior lecturer, in the Department of Cancer Research. During this period he had a year at the McArdle Memorial Laboratories in Madison as an Exchange Fellow. In 1961 he moved to the Chester Beatty Research Institute and was there until 1971, during which he obtained his D.Sc. (London) in 1965 and his F.R.C.Path in 1967. He was also associate pathologist and honorary consultant to the Royal Marsden Hospital in this period. By this time he had already published very widely and his advice was sought by various industries. In 1971 he joined the Tobacco Research Council as their research coordinator, but in 1973 he decided to set up as an independent consultant in toxicology, experimental pathology, and cancer research. This proved highly successful and his advice continued to be sought over a long period of time by a widening range of food, drug, chemical, and tobacco companies.
Roe’s early work was concerned with mechanisms of carcinogenesis and in particular demonstrating the profound effect on tumor incidence rates of the order in which chemicals were applied. These experimental initiation/promotion studies on the skin, many published with his colleague Myer Salaman, underlined the complexities of the cancer process. His writings emphasized this, pointing out that cancer is a group of diseases, each with multiple causes.
In the mid 1970s he was involved in thought-provoking studies on cancer and aging. It was held by many that the much higher risk of most cancers in the old was due to a decrease in the body’s resistance to cancer with advancing age. Based on studies in which the age at start of exposure to chemical carcinogens varied, Roe and his colleagues showed that, at least under some conditions, cancer incidence rates depended wholly on the duration of exposure and not at all on the age at the start of treatment. This observation was of profound importance to the understanding of mechanisms of cancer.
Roe’s career began when the use of rodents to test new chemicals for carcinogenicity was in its infancy. While the assay’s fundamentals have barely changed over several decades, he was well aware of its strengths and limitations and took a keen interest in contentious issues relating to it, in particular the optimum diet to use for the laboratory animals. He planned and executed the huge Biosure study, which showed that restricting the dietary intake of untreated rats to 80% of their usual ad lib. intake dramatically reduced the incidence of cancers of various types. He pointed out that laboratory animals were typically overfed and obese, and that variations in cancer incidence between untreated and chemically treated rodents may arise not because the chemical had any true carcinogenic effect but because it happened to affect the appetite of the animal. He coined the term “pseudocarcinogenicity” to describe the enhancement of tumour risk by a nongeno-toxic mechanism (such as endocrine disturbance secondary to overfeeding) in physiologically abnormal animals.
Roe was conscious of many important ways in which inadequate use of statistics could produce misleading results, and was one of the first to be keenly aware that analysis of tumor incidences without adjustment for survival differences can lead to erroneous conclusions as to whether a chemical is deemed carcinogenic or not. He worked closely with statisticians such as Malcolm Pike, Richard Peto and, during his period of independent consultancy, Peter Lee. In the late 1970s, Roe and Lee collaborated in ideas for the development of a computer system for pathology data which would allow relevant data to be collected and statistically analysed in an unbiased way. With the major contribution of the statistician John Fry, this ROELEE system has continued development to this day.
In recognition of 50 years of scientific endeavour, a fitting tribute was paid to him in 2002 when a special issue of Food and Chemical Toxicology was published in his honour. He had been closely associated with this scientific journal since its inception in 1964. Leading scientists, from the UK, other European countries, and the United States who knew him well, submitted papers to this special issue as a tribute to a man who had engendered so much respect in the pathology, cancer research, and toxicology communities. He will be sorely missed by his colleagues in the British Society of Toxicological Pathologists and by all who knew him or who were touched by his contribution to pathology, over the last 50 years.
These notes were prepared largely by Peter N. Lee, with contributions from BSTP members.