CABI Blogs: hand picked... and carefully sorted: BSE: Twenty years old

Twenty years ago, a paper appeared in the Veterinary Record recording a new disease in dairy cattle. The syndrome had been seen in cattle in England for a couple of years but with the publication of the paper by Wells and others, the disease was described and named, and the new term bovine spongiform encephalopathy (BSE) entered the English language. This official name soon gave way, in the media, to the more catchy term mad cow disease.

Few people reading that original paper back in October 1987 could have imagined the full consequences of the outbreak as it grew to a peak of more than 30,000 cases in cattle in 1992. Public distrust of the government and scientists also grew, as original claims for the safety of beef were shaken by the arrival of a new form of Creutzfeldt-Jakob disease (v-CJD) in humans. The prospect of an epidemic of v-CDJ in humans on the scale of the BSE outbreak in cattle was truly terrifying to consider. The annual number of v-CJD cases in the UK rose to a peak of 28 in the year 2000, after which it has gradually decreased. Thankfully the epidemic of new-variant CJD did not reach the levels of BSE in cattle, although this was of little consolation to the families of the victims of that terrible disease. To restore public confidence in British beef and to recapture export markets, which had been closed, cattle over 30 months old were excluded from the food chain and stringent regulations on ruminant protein in cattle feed were enacted. The epidemic in the UK became the most expensive peace-time crisis for the Government.

The arrival of BSE and v-CJD prompted an upsurge of research on the causes and pathogenesis of these diseases, and their relationship to other similar diseases such as scrapie and chronic wasting disease of deer. The theory most widely accepted is that the disease is caused by an abnormal form of a protein, the prion protein, which is resistant to both heat and protease enzymes. The abnormal prion accumulates in the cells of the nervous system, causing nervous symptoms and finally death. The affected brain tissue takes on a spongy appearance. The abnormal prion protein appears to act like an organism, being able to replicate itself. The disease appears to be transmitted to cattle (and other species) from the practice of including ruminant protein in feed.

Although there is a substantial body of evidence to support this theory (not least the decline of the UK epidemic following the removal of ruminant protein from cattle feed) there have been several other possible causes suggested, including viruses, bacteria, and chemicals. For example, one suggested cause of the disease was organophosphates, as UK farmers were obliged to use these pesticides to combat warble fly. Although the organophosphate theory sounded plausible, attempts to create BSE experimentally using the pesticides failed in tests on cattle, so there has been no clear experimental evidence to support that theory. Another theory suggested that the infectious protein originated from human remains (rendered protein imported from India) included in cattle feed.

Other theories have included infectious agents as the cause. One such theory is that the disease is caused by bacteria and that prions are involved in the pathogenesis but are not the cause. A paper recently published in the Journal of Medical Microbiology (DOI 10.1099/jmm.0.47159-0) claims that Spiroplasma, small wall-less bacteria, can induce spongiform encephalopathy in ruminants.
The paper reports on experimental work carried out in Baton Rouge, Louisiana, where Spiroplasma mirum isolated from rabbit tick was inoculated into the brains of deer, sheep and goats. The deer developed nervous system symptoms and showed post-mortem signs of spongiform encephalopathy. Sheep and goats did not show nervous symptoms but post-mortem examination of their brains showed clear signs of progressive spongiform encephalopathy. Spongiform encephalopathy was also induced in deer and sheep inoculated with Spiroplasma isolated from brains of sheep and goats with the disease.

The idea that bacteria are behind transmissible spongiform encephalopathies (tSE) is also suggested in another recent paper, by another author. H. Peter Schmitt of Heidelberg University (Germany). He suggests that rather than the bacteria themselves, it is the bacterial toxic proteins (BTPs) that cause tSEs and diseases such as Alzheimer’s disease. His theory is that BTPs can meet the key-proteins of Alzheimer’s disease (AD) and tSEs in the lipid-rich domains of the plasma membrane called rafts. This then could enable them to start a large variety of unfavourable molecular events, eventually resulting in pathogenic cascades as in AD and the tSEs. The reasoning involves some pretty complicated biochemistry which would be out of place in a blog like this, but the reference is listed below for those who are not deterred by biochemical detail.

So are tSEs caused by prions, bacteria, bacterial proteins, organophosphates or some combination of these? Even looking through the published evidence (there are nearly 5000 references on BSE, scrapie and the other tSEs on the CAB Abstracts Database) one is always left with the feeling that there is some vital part of the story missing. The 20 years of research has certainly increased the understanding of these strange and terrifying diseases, but there is still much more to learn about them. I suspect that in 20 years time (unless the BTPs have got me) I will still be seeing new theories trying to explain BSE, CJD and the other tSEs.

Wells, G. A.; Scott, A. C.; Johnson, C. T.; Gunning, R. f.; Hancock, R. D.; Jeffrey, M; Dawson, M.; Bradley, R., 1987. A novel progressive spongiform encephalopathy in cattle. Veterinary Record, Oct 1987; 121(18), 419 - 420.

Schmitt, H. P. 2007. Profiling the culprit in Alzheimer’s disease (AD): Bacterial toxic proteins – Will they be significant for the aetio-pathogenesis of AD and the transmissible spongiform encephalopathies? Medical Hypotheses 69 (3), 596-609. DOI:10.1016/j.mehy.2007.01.022

Bastian, F.O.Sanders, D. E.; Forbes, W. A.; Hagius, S.; Walker, J. V.; Henk, W. G.; Enright, F. M.; Elzer, P. H. Sproplasma spp. 2007. From transmissible spongiform encephalopathy brains or ticks induce spongiform encephalopathy in ruminants. Journal of Medical Microbiology, 56, 1235-1242. DOI 10.1099/jmm.0.47159-0