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One fibre or many; what causes mesothelioma?
  1. A Seaton
  1. Department of Environmental and Occupational Medicine, Aberdeen University Medical School, Foresterhill, Aberdeen AB25 2ZP, UK; a.seaton{at}abdn.ac.uk

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In a recent case (00/TLQ/1284) in the Queen's Bench Division of the High Court in England, a widow sued on behalf of her husband who had died at the age of 60 of mesothelioma. Unusually for such cases, Mr Justice Curtis found for the defendants, and the grounds for his judgement were sufficiently curious to be of general interest and worthy of debate.

It was not disputed that the deceased had been exposed to substantial quantities of asbestos during two periods of employment, nor that there had been a breach of statutory duty by his employers at that time. The judgement was based, however, on the expert and agreed opinion of “two most highly qualified medical men”. In their joint report and oral evidence, the judge believed these doctors to have stated that mesothelioma is the consequence of malignant transformation in a single cell, the result of a hit by either one or several fibres. This led the judge to reason that, although a fibre or fibres inhaled during one or other period of employment may well have led to the fatal cellular transformation, it was not possible to say which, and he was therefore unable to find either responsible.

In coming to his judgement, Mr Justice Curtis made a distinction between causation and risk factors. In his words “the only relevance of the number of fibres is in connection with the risk of contracting the disease”. He was thus dissuaded from being influenced by any evidence that might have shown a relationship between risk of mesothelioma and dose of asbestos, although there is much such evidence from studies both of human lungs and of animals.

I have heard the view expressed before that one fibre causes mesothelioma. It depends what you mean by “cause”. It is in one sense obvious nonsense. We all have millions of asbestos fibres in our lungs and the likelihood of us developing mesothelioma depends on how many millions. This means that the disease is dose related. The problem in this case arose from confusing the disease mesothelioma with transformation in a cell, which may be a factor in the development of the disease. Take the case of the butterfly flapping its wings in the Amazon rain forest. It may be possible for an ingenious QC to prove that the hurricane that hit the coast of west Africa was caused by that insect's action, but the other side would surely point to other risk factors that, taken with the action of the butterfly, contributed significantly to the disaster.

Is it really possible to say that the only and necessary cause of mesothelioma is transformation in a cell? Are we sure that the milieu in which that cell lives and divides is not influential? Are we sure that inflammation in the tissue involved is not an important precondition for the development of the disease? Are we sure that the action of asbestos on other cells does not interfere with the natural defences that would otherwise eliminate the transformed cell? Are we sure that genetic factors and viruses do not also determine whether the transformation occurs or succeeds in overcoming the body's defences? Or looked at another way, experimentally, how many rats would have to be used to produce one mesothelioma after injection of one fibre into the peritoneum? Of course, no one has ever shown that one fibre causes mesothelioma. All that has been conjectured is that the malignant cells that form part of the tumour may be the genetic offspring of one transformed cell.

The judge appears in this case to have been persuaded to accept a naïve view of causation—that disease has one ultimate cause. Most who have studied the causation of disease would argue that the likelihood of disease occurring in any individual is influenced by multiple factors, the outcome of inherited and acquired susceptibility and environmental precipitants. In the case of mesothelioma, a very heavily asbestos exposed individual may have a one in 10 lifetime risk of the disease. Most of us, with very small incidental exposures, have about a one in 1 million annual risk. The risk varies with the length and intensity of exposure, as assessed by the individual's occupational history. We know from animal studies that asbestos fibres do indeed cause mesothelioma, so this evidence of a dose related association strongly suggests that factors other than transformation of one cell are also, and critically, responsible for the disease. Among these is likely to be inflammation in the pleura initiated by the presence of many fibres. Such inflammation may not only result in malignant transformation of many cells, but may also inhibit the natural mechanisms whereby such cells are eliminated. If this is true, and it is certainly more plausible than the one fibre theory, then mesothelioma is caused by the access of large numbers of fibres to the mesothelial tissue. Since it is a dose related disease, it may be argued that all exposures to asbestos before a critical time would be expected to have contributed to the causation of the disease. Thus, attribution of blame should be on the basis of relative intensity and duration of exposure in different trades.

The moral of this story is that lawyers are clever people and part of their business is the meaning of words. The word “cause” is one that requires a bit of thought. My Shorter Oxford Dictionary devotes a column to it.

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