Big decisions based on small numbers: Lessons from BSE

The epidemic of bovine spongiform encephalopathy (BSE) has been the most ex pensive disaster ever to have befallen farming in the UK, It is believed to have led to a new form of spongiform encephalopathy in humans and as yet t here is no way of knowing how many people will die of this disease, In orde r to curtail the BSE epidemic major decisions had to be made, often on the basis of inadequate scientific data. These data may ha,le been derived from experiments using small sample numbers. Here we review some examples of wh ere this has happened, sometimes with a beneficial outcome and sometimes wi th a misleading outcome. The identification of BSE as a new disease depende d on precise neuropathological observation of a small number of cases rathe r than the obvious occurrence of large numbers of sick animals, Similarly, the recognition that BSE may have led to disease in humans was based on the neuropathological and clinical picture of new variant Creutzfeldt-Jakob di sease (CJD) rather than on an increase in the number of cases of CJD in the UK, Early in the BSE epidemic the possibility that disease could be matern ally transmitted from cow to calf was raised, mainly because of a belief th at such transmission occurs in scrapie disease of sheep. But, nle argue, th e evidence for maternal transmission of scrapie, collected in the 1960s, wa s based on small numbers and is inadequate. Subsequent I research has shown a, en substantial genetic component in scrapie and epidemiological data sh ow no excess risk in the offspring of affected ewes relative to the risk in the offspring of affected rams. An experiment to determine whether materna l transmission occurs in BSE was flaw ed and was unable to distinguish betw een maternal transmission and genetic susceptibility to environmental conta mination, An assessment of the risk of BSE to humans depends on determining the levels of infectivity in tissues and transmissibility across species. Data on both of these are deficient so it is not possible to predict how ma ny people in the UK or elsewhere will become affected with new variant CJD in the next fifty years. The assessment of whether BSE could be transmitted to sheep and whether sheep therefore pose a risk to humans is hampered by a serious lack of evidence about the epidemiology of scrapie in the UK and elsewhere. The UK has paid a heavy pl ice for the BSE epidemic but lessons should be learned from the experience. Every country should have a Specifie d Offals Ban even if it has no cases of BSE because, by the time it has, it will be too late. Furthermore, the occasional case of BSE should not be re garded as insignificant since it may be the harbinger of an epidemic in the making.