Spiroplasma proposed as cause of Mad Cow Disease
Organophospates and BSE: Mark Purdey

Theories of Mad Cow Disease

JAMA  August 14, 1996
DC Capital Conference spring 1996
A dissenting view on the cause of mad cow disease came from Frank O. Bastian, MD, profesor of pathology at the University of South Alabama College of Medicine, Mobile, who outlined his theory that mad cow disease is caused by a conventional microorganism, a spiroplasma. Bastian spoke at a symposium held by the National Foundation for Infectious Diseases.

Bastian regards the prion theory as a red herring. The cause of transmissible spongiform encephalopathies (TSEs), he says, is a conventional microorganism--a mollicute or, more specifically, a spiroplasma. "The infection-related protein is produced by the host in response to the infection," he says. He bases his conclusion on 3 premises:

1. Twenty years of his research indicates a role for spiroplasma. The evidence includes the following: spiroplasma-like inclusions were seen in brain biopsies from patients with CJD (Arch Pathol Lab Med. 1979;103:665-669); spiroplasma internal fibril proteins are identical morphologically to those seen in TSEs; the spiroplasma proteins show immunological cross reactivity with the TSE proteins (J Clin Biol. 1987;25:2430-2431); and spiroplasma, when inoculated into rodents, produces a similar neuropathology (Amer J Pathol. 1984;114:496-514).

Spiroplasmas, discovered in 1976, do not have a cell wall; they blend with the host's cell membranes. A labeling marker would help identify them, but developing one is difficult because spiroplasmas are hard to cultivate. No more than half the known strains are culturable, says Bastian.

2. The PrP in these TSEs is a product of the infection. "It is a modified host protein and may play a role in the pathogenesis of the disease, but it is not the agent because there are numerous reports that the protein can be separated from infectivity. Also, it is found in inclusion body myositis, a condition unrelated to CJD," says Bastian.

3. The immune system is involved. The gene for the host protein is located on the chromosome in the region of the major histocompatibility complex (MHC) in the mouse. "Occasionally, you see elevation of immunoglobulins; there are morphological alterations of the leukocytes; there is leukopenia," Bastian explains, "and autoantibodies are characteristically seen in the late stages of both experimental and naturally occurring infection. There is partial MHC restriction in both human and animal disease."

The immune reaction seen in these spongiform diseases can be explained by superantigen activity, Bastian says. He notes that, normally, an antigen is presented to the cell surface in the MHC and interacts with the T-cell receptor--the antigen lying in a groove in the T-cell-MHC sets in motion the standard reaction. A superantigen, on the other hand, binds outside the groove of the T-cell and interacts with the MHC. This results in some immunoglobulin production, but only transiently. The major effect is clonal deletion of T cells, resulting in a state of immune tolerance. Autoantibodies can also form.

Bastian proposes that, in spongiform diseases, PrP presumably acts as a superantigen. The question, he says, is what is producing the superantigen. He proposes that it is a bacterium. He says he is especially excited by the fact that the mollicutes cause superantigen production, adding that it is noteworthy that inclusion body myositis, a condition in which prions are seen, is an established superantigen disease.

Bastian is concerned because of recent reports that disease has been transmitted to macaques given BSE-containing contaminated material (Nature. 1996;381:743-744). The pathology in the monkeys is identical to that seen in the recent human cases of CJD in Great Britain and appears to confirm that these cases were the result of transmission to humans of BSE, Bastian says.

He also notes that investigators have just reported transmitting scrapie to mice from hay mites gathered from farms in Iceland where scrapie is endemic (Lancet. 1996;347:1114). Bastian says he is virtually certain that these hay mites contain spiroplasma, noting that the investigators have not so far found PrP in the mites.

"Clearly, the agent has become so virulent that it can easily jump species barriers. This makes it very dangerous," says Bastian, "and shows the need to intensify research in this area."

To control CJD, Bastian said the first step is to stop feeding offal to cattle and second, "we must develop a preclinical method of detecting the causative agent."

The key to accomplishing this is looking for a conventional invasive organism, rather than a host protein, in these infected tissues, Bastian said. "Once we have developed a method of detecting the organism, we will be in a position to do surveillance studies, find out where the disease is, and deal with any potential problems that might arise." He added, "Perhaps success in this area will also allow us to eradicate scrapie, which we've known about for 200 years."


Mark Purdey: Organophosphate theory of BSE

Purdey, Mark
Med-Hypotheses. 1996 May; 46(5): 445-54

This paper elucidates the flaws in the official hypothesis that bovine spongioform encephalopathy originated from alterations in the way that scrapie-contaminated cattlefeeds were manufactured in the UK. An alternative hypothesis is proposed that cites exposure of the bovine embryo to various specific high-dose lipophilic formulations of organophosphates, such as the high-dose phthalimide containing organophosphate phosmet, (which were applied compulsorily and exclusively in the UK during the 1980s/early 1990s) as the primary trigger that initiated the deformation of prion protein and the onset of the bovine spongioform encephalopathy epidemic. The multi-site binding metabolites of these organophosphates penetrate the fetus, covalently phosphorylaing various active sites on fetal prion protein.

The extra charged phosphate groups left on aged prion protein blocks both proteases and chaperones from accessing their catalytic/bonding sites, creating the undergradable, misfolded isoform of prion protein, PrPsc. The resulting abnormally phosphorylated PrPsc aggregates to freshly synthesized PrPc, transforming it into same; due to a system of positive feedback invoked by the organophosphate-induced blockage of a prion protein-specific protein kinase. Both the timing, distribution and dynamics of usage of these specific organophosphates correlates with the epidemiology of bovine spongioform encephalopathy as well as accounting for the 23,000 cattle that have developed the disease, yet were born after the 1988 ban on scrapie-contaminated cattlefeed.