MAD COWS OR MAD SCIENTISTS?

The smoke and flames from funeral pyres for hundreds of thousands of British cows are fading into distant memory, but the fear of this disease affecting livestock or wildlife continues to circulate the globe.

Most people do not realize that there is a non-infectious explanation for Mad Cow disease and other spongiform encephalopathies and chronic wasting diseases. This is due to the reluctance of scientists, health and agriculture bureaucrats and most of the media to question a theory that affects public health once it is active policy.

One man, Mark Purdey, has turned himself from organic dairy farmer into an amateur scientist and globe-trotting epidemiologist to doggedly continue building the major alternative theory.

The infectious theory of Mad Cow disease not only resulted in the possibly unnecessary destruction of hundreds of thousands of cows, but it diverted attention from other causes of health problems facing livestock and wildlife. It created a fear of eating beef (perhaps not entirely misplaced, but for the wrong reasons) and resulted in the circulation of tons of toxic materials from the slaughtered cows into the atmosphere. It also prevented investigations into alternative solutions to the epidemic of disease, even though these might be cheaper, more constructive and far less destructive.

The dominant belief is that Mad Cow disease (also known as Bovine Spongiform Encephalopathy or BSE) and the related diseases Scrapie in Sheep and vCJD (variant Creutzfeldt Jakob Disease) in humans are caused by a prion, a mutant protein. These semi-living beings are thought to be able to withstand temperatures that would kill the hardiest bacteria, viruses and parasites. It is believed that this allowed them to be transmitted from sheep to cows through the rendering of sheep brains into MBM (Meat and Bone Meal) protein supplements for cows.

An apparently unrelated health problem in cows that existed before Mad Cow disease was warble fly infestation. These flies lay their eggs in a cow’s skin, causing health problems and reducing the value of cow hides. To combat this, in the early 1980’s the British government mandated the use of heavy doses of organophosphate insecticides. These were poured in an oil-based liquid along the spinal column of cows. It was intended that they be systemic, absorbed into the cow’s body, as it was believed that this was necessary to provide full and enduring protection from warble flies.

Mark Purdey was one of a handful of farmers who refused to use organophosphates (such as Phosmet) on their cows in 1982. He was concerned that the high doses would damage the health of his cows because the application was so close to the spinal column. He was also concerned about the health of people who drank milk from his cows. In 1984, Purdey won his court fight, and gained the right to use less toxic methods to combat warble fly.

When the first cases of neurological problems were reported in cows in 1985, Purdey felt that his avoidance of these pesticides had been vindicated. However, researchers and the British Government had a different idea, blaming the rapidly emerging disease on the recently postulated prion, based on the detection of protein plaques in the brains of sick cows.

Purdey started to publicly argue his theory that organophosphate pesticides were actually the cause of neurological problems, attracting some attention, and seriously annoying the British scientific establishment and government who were starting to act as if the infectious theory was fact.

Purdey noted many inconsistencies in the prion theory. Cows were supposedly infected by feeding on supplements containing the brains of sheep with Scrapie, yet Shetland Islanders had been eating potted sheep brains for centuries without similar diseases occurring. He also noted that British byproducts were exported around the world, yet the 170,000 British cases of BSE far outnumbered the total in the rest of the world. Cases of BSE had been found on organic farms with cows brought in from outside, but not on those raised from birth on the organic farms, even though organic farming rules allow restricted amounts of the suspect MBM feeds. Other ruminants, such as goats and sheep, were not affected by Mad Cow-like diseases in England, even though they were fed MBM supplements. Conversely, several antelopes at the London Zoo and cattle at the Liscombe experimental farm developed BSE, but had never been fed MBM supplements.

When BSE was found in other countries it was in places like Bretagne in northwest France where organophosphate pesticides were first encouraged by the French government. As in the UK, BSE cases first occurred a few years after the pesticide program was initiated. The lower number of cases may be due to the lower doses used, the use of annual treatments (as opposed to twice a year in the UK) and because the program was not mandatory.

As further evidence, the decline in BSE cases in the UK began about the same time the warble fly eradication program ended.

British cases of vCJD in humans also fit the environmental theory. The disease was found in some long-term vegetarians and in humans who had never eaten cow brains. There is no good explanation of why cows could only get BSE from eating sheep brains, but humans could get it from eating only other parts of cows.

Although there was a great deal of panic, there were actually few cases in humans. Purdey noted that about 80% of the 82 cases were in rural areas, even though more than 80% of Britons live in urban areas. One cluster in the Weald district of Kent is in a hops growing area where organophosphate pesticides are used at 100 times average levels for all crops.

Purdey lobbied for government funding to test his research. Eventually, he did get a small amount, and Dr. Stephen Whatley of the University of London was able to show in a test tube that organophosphates were found to produce 3 of the 4 protein transformations required to create the mutant prion protein. A victory, but also a major defeat. The UK BSE inquiry admitted that "the door is not yet closed on the possibility that OPs [organophosphates] played a role in rendering cattle susceptible to BSE infectivity," but the infectious theory was still cast in the primary role because of the inability of Whatley to show all four transformations.

Purdey was not about to give up. He felt that there must be a co-factor that he had missed. To find it he went on a tour of places in the world where spongiform encepalopathies had existed in animals or humans for some time, collecting samples of soil and feed. In these places, where organophosphates had little or no use, he found extremely high Manganese levels and low Copper, Selenium, Zinc and Iron. He did not find this in geographically similar areas where no illness was found. The causes of this mineral imbalance varied, including acid rain, volcanic emissions, lead-free gasoline production, emissions from steel, glass, ceramic, dye and munitions manufacturing and the take-off zones of major airports.

BSE-like diseases were found in Colorado among deer and elk in an area of the front ranges where overpopulation often forced starving animals to graze on pine needles. These showed very high levels of Manganese, perhaps due to acid rain from upwind smelters. In Iceland, Purdey found Scrapie associated with similar high Manganese/low Copper soil conditions. In Slovakia the two clusters of CJD are close to ferromanganese factories and glassworks (heavy users of Manganese). These cases may well be related to the almost eradicated occupational disease known as "Manganese Madness" which occurred among miners exposed to poorly ventilated working conditions. Its symptoms and brain pathology are similar to spongiform encephalopathies.

Purdey was not just randomly testing for mineral abnormalities. Copper is a constituent of the normal prion protein, and Manganese could be a replacement when Copper is deficient, or when Manganese is present at high levels, such as in many mineral supplements for cattle. It is at this point that Organophosphates re-enter the theory. They can remove copper from the body, leaving the door open for Manganese (or other similar metals) to replace it in the prion protein. This results in a non-functional conformation of the molecule, particularly when Manganese is from the 2+ form to the oxidative 3+ and 4+ forms.

Recently, Purdey traveled to Groote Eylandt, an island north-east of Australia where 25% of the world’s Manganese is currently produced. About one in thirty people in the largely aboriginal Agurugu village, where the fine mine dust regularly settles most heavily, have Groote Syndrome, a progressive neurological disease. Researchers supported by the mining company hypothesize a genetic defect introduced by Portuguese sailors 300 years ago, even though this theory does not explain why some white mine workers also have this syndrome, nor does it explain the emergence of this syndrome since open pit mining began in the 1960s.

Purdey’s theory was now multi-factorial. Organophosphates were a major factor, but the copper/manganese imbalance could be exacerbated by animal feeds or mineral supplements. Similar situations could occur where the soil is low in the antioxidant metals and high in Manganese.

After extending the theory, David Brown, a researcher at Cambridge University performed experiments that incorporated high Manganese and low Copper conditions and was able to reproduce all four protein changes in vitro, thus providing full laboratory confirmation that Purdey's theory is at least plausible.

At the height of the Mad Cow frenzy, the British government invited Purdey to make a detailed proposal for research funding. Predictably, after sitting on the proposal for more than a year, they rejected it, and then funded two of its reviewers for some of the studies suggested by it. A cynic might conclude that they had asked for a grant proposal solely to have Purdey reveal his arguments and thoughts in full detail, so that they could then fund some ‘reliable’ researchers to debunk them, without giving Purdey resources that might strengthen his arguments.

Interest in Purdey’s ideas is still growing in a grass roots fashion, although slowly, and usually beneath the radar of major media outlets. Purdey has a small grant from the US Fats and Protein Research Foundation, supervised by Dr. Larry Berger of the Animal Science Lab in Urbana, Illinois. Purdey recently gave 14 lectures in Japan, some Slovakian researchers are studying the influence of Manganese and Copper on familial and sporadic cases of CJD. Some British universities are also quietly investigating in this area.

Purdey is attempting to obtain brain samples from Groote Eylandt to test for manganese and copper levels, and has persuaded one local GP there to see whether a chelating drug that removes Manganese will have beneficial effects.

Purdey is now investigating whether ultra-violet light is an additional factor in the development of SE diseases, perhaps in concert with a haze of terpines from the pine trees that often grow at these elevations. He hypothesizes that the eyes could act as a trigger, because of their concentration of nerves exposed to light.

Purdey and other researchers have turned up many potential factors that could stimulate the development of spongiform encephalopathies and chronic wasting diseases.

If some or all components of this theory prove to be valid, the solutions to these devastating diseases could be incredibly simple. It may also open new avenues of research into mental illness. Supplementation of cattle feeds with minute amounts of copper and regulation of the manganese levels could work near miracles, at minimal cost. Chelation could be used to reduce the levels found in people or animals suffering from these illnesses. Yet, it is likely that governments and the scientific establishment will continue to concentrate their efforts almost exclusively on infectious agents and genetic defects, suppressing anybody brave enough to argue against them on this or other health issues.

Purdey M. Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant cofactors Cu, Se, Fe, Zn. Medical Hypotheses, 2000; 54(2), 278-306

Brown DR et al. Consequences of Manganese replacement of Copper for prion protein function and proteinase resistance. EMBO J, 2000 Mar 15; 19(6): 1180-6.

David Crowe writes on medical and telecommunications topics and is a regular contributor to redflagsweekly.com. He has a degree in biology and mathematics and has peer-reviewed papers published in the areas of biosystematics and computer science.

I know Barry, and your statement is true, the work was recognized as seminal as soon as it was released in, if I recollect, Milan. Can you fill in my recollections on several items here? Also note ProMed has voluminous reports on scrapie, CJD, BSE, and recently vCJD .

Now questions:"supplements containing the brains of sheep with Scrapie, yet Shetland Islanders had been eating potted sheep brains for centuries without similar diseases occurring."

Did these sheep have scrapie?

"After extending the theory, David Brown, a researcher at Cambridge University performed experiments that incorporated high Manganese and low Copper conditions and was able to reproduce all four protein changes in vitro, thus providing full laboratory confirmation that Purdey's theory is at least plausible"

??? Please describe " all four protein changes" ... this is too nebulous to be useful

This a notion that needs to be attended to or discarded as junk science. I admit I am intrigued by the notion. My earliest contact with prion-like diseases was in graduate virology in the early eighties. Does this notion fit the scenario of KuriKuri? ( or was it Kuru?) or the neurological wasting disease that was first recognized on a particular Pacific island associated with a cannabalistic population who ate the brains of the dead ? Interestingly, the brains were cooked over an open fire in the skull. The focal question is this; even at high temperature, the very resistant protein is not denatured, but is the protein, prion, the template that sets in motion the incorrect folding of all the other like proteins; much like a wrinkle in a bolt of cloth will perpetuate that wrinkle as long as the cloth is rolled onto a spool; or is this notion somehow confused by correlation with a Cu++ /Mn++ incorporation imbalance? It is my recollection that CJD and or BSE can be induced simply by inserting the incorrectly folded prion into an animal; then subsequent like proteins will be "mis-folded" also. Is this premise implying that the proclivity to trigger mis-folding is already in place , needing only a template to initiate the mechanism ? and that the proclivity can be rendered inoperable by appropriate Cu++ concentrations ?? or lowered Mn 3+-5+ concentration? any other literature on this?

Remember that contagious pathogens have at first been suspect in noted animal disease die offs . Note the complete destruction of the British poultry industry in the 1960s or early 1970s by TURKEY X DISEASE . This turned out to be not a pathogen, but toxin present in all peanuts, aflatoxin, which was used in feed. One batch of peanuts had an abnormally high concentration of aflatoxin but all peanuts have some toxin due to the association of the underground root nodule with Aspergillus sp. fungus and its byproduct aflatoxin. This led to massive illness in the turkey flocks and destruction of millions until the culprit was recognized as the feed.

Neither of the researchers (Barry Marshall and Robin Warren) were vilified. Their research was accepted almost immediately.

I beg to differ, but then, you may have some direct knowledge of which I am unaware. As you will see below, Barry Marshall has a slightly different recollection of the process and speed of acceptance. The following are some exerpts of the story of the discovery of Helicobacter pylori with direct quotes from Marshall (the highlights are mine):

(Melissa Sweet, Sydney Morning Herald, Saturday, August 2, 1997)

There is no doubt that Marshall, 46, has been one hell of a salesman. That helps explain why he is so well known for a discovery which stemmed from the observations of a colleague, Dr Robin Warren. In the early 1980s, Warren, a pathologist at Royal Perth Hospital, had become resigned to unkind jokes from his peers about his theory that an unusual bug he was seeing down his microscope had some role in causing stomach inflammation. No-one had taken much notice because it was such an outlandish notion. Everyone knew that bacteria couldn't survive in the stomach's acid environment. They'd been taught so at medical school. Marshall was in the final stages of training to become a physician, having dropped earlier plans to become a GP because, he explains: "When I was in medical school I was given the impression that everything had already been discovered in medicine. It must have been the way it was taught. "So I never thought that medical research would be interesting, but as I did my internship ... I realised there were a lot of people who had things wrong with them that you couldn't do anything about particularly." So Marshall, who had not been known at med school as an especially conscientious type, was casting around for a research project to complete his evolution into physician. His boss suggested he check out Warren, who "was always carrying on about seeing bacteria in [stomach] biopsies". The rest, as they say, is medical history.

The pair spent several months trying to culture the bugs, succeeding only accidentally when the culture was left longer than usual because of a lack of lab staff over an Easter break. Once able to grow the bug, they could show it was a "new" organism. It was initially thought to belong to the Campylobacter family but was later declared part of a new genus, Helicobacter, which is now known to have members also infecting animals other than humans. Most importantly, however, Marshall and Warren began to gather evidence to support their medical heresy that Helicobacter pylori were contributing to many ulcers. The establishment was difficult to persuade - everyone accepted that ulcers were caused by acid, stress, spicy foods, and should be treated by drugs blocking acid production. This led to Marshall's rather dramatic decision to swallow a solution containing the bug to prove it caused disease. About a week later, he started vomiting and suffering other painful symptoms of gastritis, or inflammation of the stomach, which is now recognised as being caused by H pylori. His wife, Adrienne, was not impressed. "That's a very Barry thing to have done," she recalls. They had four young children, Marshall was working 14-hour days, seeing patients all day and doing research at night, and now he was "dreadfully ill". "I told him he had to stop it and get some treatment." He did. But his point had been made.

Marshall studied medicine at the University of Western Australia from 1969-74 and worked on the wheat bins during holidays. He and Adrienne married while still studying (she did psychology) so they could get a Commonwealth scholarship. "We wanted to get away from our parents, basically," he laughs, "but we used to eat quite a few meals at our parents' houses because we couldn't afford food." Finances are not a problem these days, of course. Marshall doesn't spell out exactly how much the discovery has earned him - he has shares in a company which makes tests and other products related to H pylori - but notes that all his children have had expensive US college educations. It seems he is in the fortunate position of seeing patients out of choice rather than necessity, with enough funds left over to pursue his research interests. He adds that he has no inclination to be a businessman full-time but is enjoying his lab at Sir Charles Gairdner Hospital and hopes to establish a biotech industry in Perth: "I can now do what I like and I don't have to do something if I don't like it." BUT the road to this point was long and hard, which brings us back to Marshall's brashness. Associate Professor Stuart Hazell, a microbiologist at the University of NSW, recalls that many medical feathers were ruffled when Marshall first began his campaign to rewrite the textbooks. "When Barry spoke he was very brash, "... that I've discovered this and that you people are going to have to relearn all your medicine because we've now worked out what is really going on'," Hazell remembers. "The vast majority of the medical profession, not only in Australia but worldwide, considered Barry to be a quack and really were extremely dismissive for a number of years." Adrienne says her husband's aggressiveness in selling his message - unlike many doctors, he has never been media-shy - was simply a reflection of extreme frustration. "It was a tremendous struggle to get his work presented and published," she says. "It was really tough to hang in there."

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Journal of Theoretics, Editor (written 2/17/99)

H. Pylori and Ulcers, a Forgotten Discovery

The association between a certain bacteria and stomach ulcers was discovered over a hundred years ago as Dr. Kidd describes.(1)

"Indeed, the effects of acid inhibitory agents were held as gospel truth whilst the use of antibiotics or metallic ions were deemed to be quackery or at least ill judged. Nonetheless, spiral-shaped bacteria had been identified in both mucosa and gastric contents of patients as early as 1889. Elegant studies had documented the infectivity of these organisms, and suggested but not proven a causative role in gastric disease."

It was until 1983, when Drs. J. Robin Warren and Barry Marshall, rediscovered this and put forth the theory that bacteria were the cause of stomach ulcers. Even after presenting a convincing discovery, it took over 10 years for the rest of the world to know about it and begin to accept it. It challenged the thought of the time that it was excessive acid that caused ulcers, besides bacteria could not live in the stomach. Dr. Thagard summarizes it as follows.(2)

"In 1983, Dr. J. Robin Warren and Dr. Barry Marshall reported finding a new kind of bacteria in the stomachs of people with gastritis. Warren and Marshall were soon led to the hypothesis that peptic ulcers are generally caused, not by excess acidity or stress, but by a bacterial infection. Initially, this hypothesis was viewed as preposterous, and it is still somewhat controversial. In 1994, however, a U. S. National Institutes of Health Consensus Development Panel concluded that infection appears to play an important contributory role in the pathogenesis of peptic ulcers, and recommended that antibiotics be used in their treatment. Peptic ulcers are common, affecting up to 10% of the population, and evidence has mounted that many ulcers can be cured by eradicating the bacteria responsible for them."

In fact, Dr. Marshall was so frustrated by the lack of acceptance of his theory, that he drank a beaker of H. pylori and subsequently developed stomach ulcers and a lot of pain. It still did not convince many. I hope that through this journal, a rational evaluation of new theories may be accomplished in a more thoughtful and less painful process than Dr. Marshall endured.

Journal of Theoretics, Editor (written 2/17/99)

1. Kidd M, Modlin IM; Digestion 1998;59(1):1-15

2. Paul Thagard, "Discovery and Acceptance,"1997

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USNEWS.COM, "Barry Marshall, A gutsy gulp changes medical science." August 20, 2001.

By Rachel K. Sobel

I drank it down very quickly, like a tequila shot," recalls Australian physician Barry Marshall of his pivotal sip. His big swig was potentially toxic, with billions of bacteria in a brackish solution. The medical resident, then 32, consumed the bugs out of sheer frustration, to prove his controversial theory: Bacteria, not stress, cause peptic ulcers.

For months, physicians had snubbed his claims. Even medical students knew nothing could survive in the highly acidic stomach. "Everybody said you're silly," says Marshall. "It seemed too incredible an explanation for a difficult disease like ulcers." But Marshall and his collaborator, pathologist J. Robin Warren, had tantalizing evidence: Nearly all their ulcer biopsies harbored samples of a corkscrew-shaped bacterium that had burrowed into the stomach lining.

Watching patients suffer drove Marshall nuts. He believed a simple cure was at hand: antibiotics. So one July day in 1984, he drank the germ, later named Helicobacter pylori. He quickly developed flulike symptoms. On the 14th day, a colleague examined his stomach lining and found the telltale inflammation that accompanies most ulcers. Marshall's immune system soon fought off the infection.

The medical community resisted. "People didn't know what to do with him, coming out and saying, 'Look, you guys are all bloody wrong,'" says Walter Pe terson, a University of Texas professor of medicine. Pharmaceutical firms loathed his idea. They had begun profiting from acid blockers?costly pills that could control ulcers. Now this outback upstart proposed a one-time course of antibiotics to cure most cases for $35. Even his wife was angry. "It was irresponsible," she says. "He was ill, he had his job as a doctor, he was running his research, and we had four small children."

Yet his bold swallow paid off. "Barry Marshall in many ways paved the way for people to believe you can't be as fixed to ideas you once thought were true," says Julie Parsonnet, Stanford's chief of infectious diseases, who later helped link H. pylori and stomach cancer. By 1994, scientists had finally digested Marshall's theory: The National Institutes of Health endorsed antibiotics as standard treatment for stomach ulcers.

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There are many more, but the point is that, at least in Marshall's own words, it was an extremely difficult process to gain acceptance for a verifiable theory, and he was vilified, at least in my, and apparently his, opinion, by many of his alleged colleagues.

By the way, this does not in any way suggest that the theory that sparked this thread is true, but merely that open minds might speed the verification process, and help those who need help a lot sooner.

Egos should not interfere with progress, but alas, the opposite is more the norm.

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