What if much of the science to date, focusing on contaminated meat, has been overly simplistic or even dead wrong?

The immediate implication would be that we would have to rethink everything already done to fight the disease, both in Britain where it began, in Europe, where it has spread, and in other nations, including the United States, where concerns are mounting about its potential to be unleashed.

Last week, in order to prevent the disease from contaminating the blood supply, the American Red Cross, in accepting the view that infectious beef is to blame, barred donations from anyone who consecutively spent three months in Britain and six months in Europe since 1980.

Presumably, anyone in those countries for that long a period would have had the opportunity to contract an infection from eating contaminated beef and then possibly pass it on by donating blood.

But, of course, this prevention strategy presumed the prevailing scientific perspective on mad cow disease and its human form, variant Creutzfeldt-Jacob disease or vCJD, is correct.

Conventional View: Consumed Infectious Agent

The viewpoint held by most scientists is that an infectious agent likely moved from sheep to cows and gained enough strength in its cross-species jump to ravage the nervous system and cause the bovine brain to appear spongy and rife with holes like Swiss cheese. This brain-destroying "mad cow" infection was further transmitted, according to this interpretation, via the rendering of carcasses, to meat and bone meal in feed. That set off the epidemic in British cows in 1986.

The human form of the disease began to turn up in Britain in 1995 when, according to the conventional wisdom, the infectious agent in cows, thought to have been passed on to humans by contaminated cooked meat products, had sufficient time to incubate and become destructive to the nervous system.

So far, about 100 people have developed vCJD and died, the majority of them in Britain. Mind and body are usually destroyed within a year.

Paul Brown, a research scientist at the National Institutes of Health in Bethesda, Md., echoing the conventional view on mad cow disease and vCJD, wrote in the April 7 edition of the British Medical Journal that it is "uncontestable" that the disease in cows is the cause of vCJD.

But not according to David Brown, a biochemist at Cambridge University, who counters that "there is no conclusive proof that [mad cow disease] caused vCJD."

Next week at a scientific conference in Quebec City, he'll discuss some of his most recent research, pointing to a possible environmental explanation of both mad cow disease and vCJD.

Controversial View: Environmental Exposure

That conference is all about manganese, a heavy metal, that is essential to life and is part of the daily diet — for example, wheat, rice and tea provide the metal — but numerous studies show that environmental overexposure to it can be dangerous to the nervous system.

Manganese can affect humans via air, water and soil.

For example, workers who have been exposed to high industrial doses of manganese have suffered tremors and muscular rigidity, hallucinations, and involuntary laughing and crying. Biochemical analysis of central nervous system tissue in humans poisoned by manganese shows that the metal can cause brain cells to die.

On the basis of his published laboratory research, Cambridge's Brown believes that manganese may play an important role in a complex process that eventually destroys the brain, both in cows and humans.

David Brown agrees with the conventional view that the key agent in the disease is a protein called a "prion." These prions are thought to keep nerve cells stable. The conventional view holds that prions can somehow become malformed and that's when they become infectious and capable of damaging the brain.

The malformed prion, then, according to the conventional view, is the infectious and transmissible agent in mad cow disease and vCJD. The infection is neither a virus, nor a bacterium.

A Metal Can Change Brain Chemistry

Brown parts company here with the conventional view, altogether dismissing the notion of an "infectious" prion. He told me: "I have [published] evidence from my cell culture experiments that shows manganese can change the prion into its abnormal [and dangerous] form." This is especially the case when the supply of copper to the cell is low.

If David Brown's research is on a correct path, then scientific and public concerns about infection from beef could eventually be dwarfed by concerns about toxic effects in the environment that cause copper levels to decrease and manganese levels to rise.

Because Brown's research shows that he can change the prion from its normal to abnormal state by manipulating the only two metals that bind to it, copper and manganese, without the need for any infectious material, he believes the reigning theory about mad cow disease and vCJD is at best incomplete, and quite likely incorrect.

So, he sees it as plausible that what is seen in the test tube may also occur in humans who are environmentally exposed to excess amounts of manganese. (The metal's ancient Greek name is manganin, which means the occult, voodoo or black magic.)

In fact, Brown's research has given a boost to the controversial theories of Mark Purdey, a farmer turned amateur scientist who has been challenging the conventional view of mad cow disease and vCJD from the start.

He has provided detailed reports to the British government's hearings on mad cow disease and has published several peer-reviewed scientific papers on the subject, including data on how manganese in the environment may play a role in both mad cow disease and vCJD.

Purdey never bought into the conventional wisdom. "It never made any sense to me," he said in an interview from his farm in Taunton, England.

Pesticides May Play Role, Too

His battle goes back to 1984 when farmers in many locales were ordered by the government to use an organophosphate pesticide (Phosmet) to fight off the warble fly, a parasite that lays eggs under the skin of cattle. Purdey, who operates an organic farm, refused to do so, went to court and won.

This pesticide, a constituent of nerve gas, was applied on the back of the cow along its spinal column.

When mad cow disease erupted, Purdey noticed that the disease occurred on farms where the pesticide was used and not on those which, like his, it wasn't. He added: "Also, no home-reared cows on organic farms have developed [mad cow disease].

Purdey then focused his attention on geographic areas where there had been reported clusters of mad cow disease, similar illnesses and vCJD. "I discovered [in sampling soil, water and vegetation] that the common factor in the environment is manganese," he explained. "In some case, huge amounts of it. Also, the amounts of copper in these areas was low."

He presented his findings in his 28-page scientific paper published last year in the journal Medical Hypothesis.

For example, in Iceland, he found high levels of manganese deposits in valleys where a sheep disease, scrapie, similar to mad cow disease flourished. Valleys with normal manganese levels were scrapie-free.

In Colorado, he found deer herds with high incidence of a mad cow-like wasting disease were eating pine needles loaded with manganese. "I brought the pine needles home and had them tested and the manganese was excessively high."

Closer to home, Purdey has also investigated several cases of vCJD in the area of the village of Queniborough and discovered that soil and water samples showed high to very high levels of manganese. In the '80s and '90s a dye-works plant operated in Queniborough. Manganese is used in dyes, he said, adding that villagers remembered days when a cloud of yellow dust would settle in the area.

All his digging around has led to a highly detailed theory for mad cow disease: In short:
     The high doses of organophosphates that were poured on the cows' spines and poisoned the bodies decreased the amount of copper in cells.
     The feed given to animals in the '80s contained high amounts of manganese, some of it derived from chicken manure of chickens fed high doses of manganese to strengthen egg shells. Supplemental powders and mineral licks with manganese were sometimes added to feed troughs.
     The depletion of copper and the high manganese changes normal prions to abnormal, thus setting the stage for disease.

Purdey believes vCJD is also likely triggered by similar environmental factors.

But NIH's Paul Brown told me that this alternative theory is among those he views as "nonsense," referring me to his BMJ paper of April 7.

In it, he states that the theory that organophosphates are involved in mad cow disease fails to account for the evidence that the disease can be experimentally transmitted.

Purdey counters that the disease is not transmitted experimentally when processed beef products are used. Only when tissue directly from cows is ground up and mixed. "Humans and cattle obviously do not eat this concentrated so-called bovine homogenate," he explained. "This is not the correct way to do science."

When the homogenate is used, theorizes Purdey, its toxicity, due to changes in its arrangement of metals, may lead to a change in prions from their normal to an abnormal state.

The NIH's Brown, also writing in BMJ, raises the question of why Japan has been mad-cow free since it uses organophosphates extensively.

Purdey's response is that Britain's use of Phosmet, unlike elsewhere, was four times the maximum dose and that it was an oil-based application that entered the cows' blood stream. "You can't just simply throw around the idea that everyone uses organophosphates the same way."

More Research Necessary

So where do we stand on this issue? Obviously the mainstream infectious model of what mad cow disease is all about holds sway and is likely to continue to do so. Unless, of course, more research funding is granted to nay-sayers like Purdey and Cambridge's David Brown that makes for compelling science and headlines.

The British government has paid some lip service to Purdey's ideas — they have been discussed in the House of Commons — and has promised him some research funding. But so far, no dice.

David Brown of Cambridge, while cautious about his and Purdey's challenge to conventional thinking on mad cow disease and vCJD, said that "science should be open to these possibilities, particularly since there is still a lot of mystery surrounding these outbreaks."

David Brown also believes that ignoring the possibility that environmental factors trigger both animal and human diseases could prevent action from being taken to clean up toxic effects that may be at the root of the problem. "We obviously need much broader research in this entire area," he said.

This is a battle that will not likely go away. And it shouldn't go away until more research is done to examine the claims — on both sides.