From Sheep to Humans: Scrapie and Creutzfeldt-Jakob Disease
by Rolf George
Professor of Philosophy, University of Waterloo
Creutzfeldt-Jakob Disease, first described in 1920, is an always fatal degenerative disease of the central nervous system and belongs to the class of transmissible spongiform encephalopathies (TSE). "Classical" CJD can run in families (15%), while other infections have followed surgical procedures and transplants of cornea or brain tissue (dura), and administration of growth hormone (5%). The remaining cases are sporadic, that is, without explanation. They are widely and irregularly distributed, with the incidence rarely higher than, and usually below, one case in a million population per year. In several countries women are infected more often, sometimes twice as often, as men are.
TSE's in other species are the bovine form (BSE), or mad cow disease, scrapie in sheep, and chronic wasting disease (CWD) in deer and elk. TSE's cross species barriers and are now found, or have been induced in, mice, cats, bisons, cheetahs, pumas, tigers, ocelots, kudus, apes and other mammals and birds. As well, BSE has crossed to humans, forming a "variant" of Creutzfeldt Jakob (vCJD)1.
Scrapie was first identified in the 18th century. It was widely thought to be hereditary until in March 1935 18,000 sheep were injected with a scrapie contaminated vaccine aimed at controlling another disease (louping-ill). A surprising aspect of the case was that the infective agent had survived weeklong storage in formaldehyde. A controlled experiment using 788 animals confirmed the transmissible nature of the disease. After four and a half years 60% of intracerebrally, and 30% of subcutaneously inoculated were clinically affected2.
Prions. There is overwhelming evidence that the agent transmitting TSE's is a rogue protein, or prion, (proteinaceous infectious particle), first described by Stanley Prusiner in 19813. It has been shown to retain its infectivity under most adverse conditions, like storage in formaldehyde, autoclaving up to 120C and years of frost and sun in abandoned pastures. Prions differ in shape from normal proteins and are not susceptible to enzymes (proteases) that normally break down proteins. They increase their number in the brain by converting normal prions, and can do so even in other species. It was shown by in-vitro experiments that the probability of infection becomes smaller as the receiving species is more remote from the donor. "This suggests that after exposure of humans to scrapie, BSE or CWD, potentially pathogenic conversion to human PrP-res [protease resistant prions] might follow, if only rarely or inefficiently... Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure..."4
Epidemiology. Thorough epidemiological studies have shown that case to case transmission of CJD is extremely unlikely. Neither could an environmental source of infection be discovered5. A route of infection from endemic scrapie via cattle to vCJD has been demonstrated, but there appears to be no epidemiological evidence for a direct route of infection from scrapie in sheep to CJD in humans. CJD occurs in Australia and New Zealand, but there is no scrapie on that continent. Occupational exposure (shepherding, abattoir work) seems to have no effect, and life long vegetarians have died from CJD6. R.G. Will notes that the incidence of CJD is independent of both the sheep population and the incidence of scrapie. "This suggests that scrapie is unlikely to be causally related to CJD, but also that any putative risk factor must be ubiquitous and independent of climatic, cultural or economic differences between countries... This has led to the proposition of spontaneous generation7 of a self-replicating protein."8 But it is also possible, as will be shown, that scrapie is transmitted through contaminated fleece and wool products from countries where the disease is endemic. If this is so, then scarcity of contamination, inefficiency of transmission to the human species, and the global reach of the wool trade will lead to a scattering of cases over the globe. Rare diseases are the result of rare exposure, minimal infectivity and inefficient transmission.
![[sheep image]](/images/2002/2/george_1.jpg)
Contaminated Fleece. The contamination of pastures has repeatedly been documented. Pastures that had housed infected animals but had not been grazed for several years have infected clean herds9. Race et al observe:
"Because scrapie agent is extraordinarily resistant to inactivation, it is likely scrapie agent derived from infected placenta would accumulate in lambing areas over a period of years, giving ewes and lambs a high probability of contact... Sheep might also be exposed to scrapie agent under natural situations when they graze pasture or rangeland contaminated by tissues of sheep that have died and decayed."10
Four classes of tissue have been ranked according to infectivity, with brain and spinal cord the most infectious and wool and hair having no detectable infectivity at all.11 It is, however, not the wool as such that is likely to transmit the disease, but contamination in the fleece, picked up from the pasture. Whatever dirt is found in the pasture is sure to end up in the fleece. Sheep are like mops (see illustration).
Wool Processing and Trade. In preparing woollen products, yarn, cloth, etc. fleece is washed at only 60C, not hot enough to destroy prions. Hypochloride, the common bleach, is effective against prions, but is not used in bleaching wool, and some wool is not bleached at all. Compare this with the recommendation by the European Commission for TSE safety of bone meal for gelatine production. This involves crushing and degreasing, a two day treatment with 4% hypochloric acid of pH <1.5, then 20 to 50 days of alkaline treatment with pH>12.5 and a sterilising step of 138-140C12. If this were done to wool, no useful product would be left. One may conclude that some of the agent is left in wool and wool products if the fleece was contaminated. Australia and New Zealand, major suppliers of clean fleece to the world market, are also importers of wool products from England, which has an estimated 5,000 to 10,000 cases of scrapie in sheep per year13, and from Italy and other countries. This would seem to explain the presence of CJD in these, and other developed countries.
But People don't Eat Wool! Until recently most researchers have concentrated on the oral route of transmission. For example, it is said of the life-long vegetarian "The only possible contact with sheep products was 20 years previously when she occasionally cut up lambs liver for her pet dog."14 Evidently, only comestible parts of sheep were considered; we do not know if she was given to knitting or wearing woollen garments. Lately the application of infectious agent to broken skin has caught more attention, with surprising results. The scrapie agent, when thus administered to mice, has about the same efficiency as inoculation by intravenous and perivenous injections: "Scarification of the skin is a possible rout of entry for scrapie infectivity in sheep, and for Creutzfeldt-Jakob disease agent in humans."15 The BSE Inquiry warns against the use of cosmetics possibly derived from BSE contaminated tallow and other ingredients.16 It is now generally acknowledged that the parenteral route of infection is more efficient than the oral,17 which would seem to be confirmed by the increased risk of CJD through frequent exposure to leather products and fertiliser consisting of hoofs and horns.18 Plainly, since the use of wool is ubiquitous in Europe, no epidemiological pattern could emerge from exposure to it.
What Next? Further epidemiological studies seem indicated. Are there countries in which the use of wool is less common, or where it is not obtained from countries with endemic scrapie? Only thirty cases of CJD were reported for all of India in the twenty years from 1971 to 1990.19 This number is startlingly small, even allowing for a very large number of undetected cases. As well, an investigation of the infectivity of wool after standard processing seems in order.
In sum, while a connection between scrapie and Creutzfeldt Jakob Disease (CJD) has occasionally been suggested,20 it is generally thought unlikely. An important argument against the disease having crossed the species barrier from sheep to humans is that there is CJD in Australia and New Zealand, but no scrapie. But the infective agent could have been imported into these countries through wool products. This would explain the world-wide occurrence of CJD, the absence of geographic patterns, and the higher incidence among women, who were more occupied than men with spinning, weaving and knitting.