Yes, I think it is very clear to all of us who are engaged in the business of assessing toxicity data that, when volumes of data are proudly presented to us after a carcinogenicity study, showing that there was a tumour in this organ or that, we look at it and we scratch our heads, and we wonder what on earth we can make of it. This is especially true when huge doses are given, with nothing to suggest what would be expected at low doses. I think very often the carcinogenicity studies are a waste of everybody's time and a fearful waste of animals. They are conducted partly because we are not sure what to do instead, and partly because they are a political gesture and a very miserable one at that.
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It has been conventional practice to test potential carcinogens using highly inbred strains of rodents. The rationale was the supposed superior reproducibility of results compared with those obtained from wild-type animals. However, that assumption can be questioned. At least three examples of genetic drift of inbred strains can be cited... Lifetime expectation [in an inbred strain of mice] of developing one or another form of neoplasm ['spontaneous tumour'] had risen from 10 to 80 percent.
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For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results.
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Data from dose-response relationships are sometimes employed to estimate the expected tumour incidence at dose levels very much lower than those which could possibly be employed in conventional [animal] experiments. A number of mathematical models have been employed in such estimates and the results obtained vary considerably. Despite these uncertainties - and the possibly greater ones in extrapolating from animals to man - such models are often employed in some quarters to estimate the likely risk to man.
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For example, the control incidence of mouse liver tumour varies between 0 and 58% in 41 NTP [National Toxicology Program] bioassays where these tumours are induced by a test chemical.
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Where others have hearts, he carries a tumour of rotten principles.
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In the course of tumour progression, it has been known for many years that mice and men are totally different.
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