More on BSE/vCJD
Authors: G. T Stewart
Journal: Journal of the Royal Society of Medicine (2002)

The expectations of promising treatments described in this update by Dr Beale (December 2001 JRSM1) are offset by his conclusion that ‘In the long term, unfortunately, there will probably be no shortage of patients in whom to try these treatments’. In saying this, Beale is accepting, without discussion, the conclusion reached by the BSE Inquiry2 that ‘BSE has caused a harrowing, fatal disease in humans’ because they too accept evidence from histopathology, chromatography and experiments in mice that a malfolded prion protein found in the brains of cattle with BSE as proof that it is transmissible to humans in meat and causes variant Creutzfeldt—Jakob disease (vCJD).

This evidence depends entirely upon evidence from laboratories. In the farmyard, dogs, cats and other animals are freely exposed to BSE but, except for rare cases in domestic cats, there is no evidence of comparable encephalopathy. Evidence from national and international surveillance shows no increase in vCJD except in proportion to the increased ascertainment3,4 which followed identification of cases of CJD in people in younger instead of ageing patients. But this is precisely what Creutzfeldt observed in his first case in 1920, a woman aged 23, which he described in clinical and pathological detail as a unique encephalopathy5. Such cases were uncommon because they were identified wrongly (Unter flasche Flagge) as multiple sclerosis and other neurological disorders which were symptomatically similar but did not show the neuronal degeneration characteristic of the spectrum of encephalopathies subsequently classified as CJD because, although exceedingly rare, they were observed more often in older patients, as described later by Jakob. Similar encephalopathies, occurring notably in sheep as scrapie, in captive and occasionally in various wild mammals are transmissible (TSEs) within and sometime across species barriers by intracerebral trans-inoculations of brain substance. BSE, the latest example, is transmissible by intracerebral or peritoneal inoculation in mice. If the mice are inbred and transgenic, the lesions resulting from intracerebral injection are similar to those of BSE and vCJD.

The surveillance which extended during the two years and nine months of the BSE Inquiry showed that all the patients with vCJD were homozygous for methionine, as are approximately 40% of the resident population of the UK. Although this could indicate a genetic predisposition to form or to accept malfolded PrP, it does not explain why vCJD is so rare in that part of the same population at highest risk of exposure to BSE, namely workers in farms, abattoirs, butchers shops, kitchens and veterinarians.

Among other points escaping attention in Beale's update, as in the Inquiry, is the entire absence of BSE in suckler-then-grass-fed pedigree herds of Herefords, Angus and other breeds except where there is contact with dairy cattle3. This suggests that BSE could be a metabolic PrP disease induced by unnatural forced feeding of animal protein to herbivores, with concomitant stress, or by conveyance of mutable strains of scrapie, or because artificial insemination from limited pools has created a genetic predisposition in dairy cattle to accommodate the novel mutation from scrapie in 1970 which the Inquiry favours presumptively as the origin of BSE. To say the least, these and other uncertainties cast doubt on Beale's endorsement of the scientific prognosis that, among all humans who have ever eaten beef from herds with BSE in or from the UK, there will be (within confidence limits of zero to infinity) no shortage of patients who develop a questionably new, ultimately fatal encephalopathy.