The rise of mad
cow has caused an explosion of research into the TSEs (Want The Why Files
guide to mad-cow lingo?).
The causative agent has some remarkable properties.
tiny, able to pass through a filter that stops most viruses.
tough, able to survive thermal, radiation and chemical treatments that
kill bacteria and viruses.
not a nucleic acid. Nucleic acids are the basic component of DNA and
RNA, the chemicals that carry life's genetic code. Viruses, bacteria,
and just about every other infectious agent contain either DNA or RNA.
In 1982, Stanley Prusiner,
a biochemist at University of California at San Francisco, suggested a radical
idea: the agent was a rogue protein -- a "prion." Unlike all agents known
to cause infectious disease, this agent contained neither DNA nor RNA.
are sometimes compared to beta amyloid protein, which form brain insoluble
plaques in Alzheimer's disease.
In its normal, soluble shape, amyloid protein causes neither plaque
C. Peitsch, Glaxo Institute of
Molecular Biology, Geneva, Switzerland.
Proteins are huge,
complex molecules whose function is heavily influenced by shape. Prusiner
hypothesized that normal prions twist into a shape that both causes disease
and, chain-reaction fashion, distorts other prions into a new shape, which
has new and dangerous properties.
deemed the hypothesis heresy. Proteins are workaday molecules that reflect
genetic coding; a response to, not a carrier of, information. And since
proteins don't reproduce, how could they "multiply" and cause disease?
blame a virus
As virologists searched in vain for a viral explanation for the disease,
Prusiner and his colleagues gradually built their case. Today, although
a few scientists consider prions a marker rather than a cause of TSEs,
the prion hypothesis is well accepted. "It's becoming really clear that
the agent is this abnormal protein; it's not formally proven but almost
all the data we have supports this idea," says Judd Aiken, a TSE researcher
at the University of Wisconsin-Madison. He says most scientists "are proceeding
on the assumption that abnormal prions are the sole cause of disease"
of basic questions remain: Although normal prion sits on the surface of
cells in the nervous and immune systems, its function is unknown -- Aiken
suggests it may be involved in binding metals to cells. And exactly why
"good" proteins distort into "bad" remains to be tracked down.
Still, lots has
been learned about prions and TSEs in the past few years.
John Collinge at St. Mary's Hospital in London recently reported
that mice which received prion-infected extracts of mouse brain had
diseased prions in their brains, even though they did not appear ill.
The mice infected other mice, satisfying one of the Koch postulates
on the causation of disease. (Want to jump ahead for coverage?)
While some observers deemed it not cricket
to extrapolate from rodents to larger animals, the study did raise the
danger of "silent carriers" of TSEs (see "Experts Downplay..." in the
bibliography). Independent prion scientist
Tom Pringle likened
the situation to Typhoid Mary, an English woman who spread the disease
even though she didn't have symptoms.
veterinary pathologist Lucien van Keulen used an immune-marking technique
to map scrapie infection in sheep. After five months, prions accumulated
in lymph tissue and nerve fibers in the small intestine. After 10 months,
nerves serving other organs were affected. By 17 months, the spinal
cord was involved, and by 26 months, the animal was dying of scrapie
(see "Prions: A Lone Killer..." in the bibliography).
can change for the worse over time. Aiken, for example, passed a mink
TSE, identified by the late University of Wisconsin-Madison virologist
Richard Marsh, through hamsters, and found that the agent acted faster
in successive generations. The first hamsters to receive the mink TSE
generally outlived the disease, which took hundreds of days to incubate.
When brain material from those hamsters was injected into other hamsters,
the disease struck faster. By the third generation, there was a "tremendous
shortening -- it has adapted to the new species," Aiken says. Why did
it take two to three passages for the agent to stabilize? Because, as
Marsh had suggested years ago, two strains of prions existed in the
first passage, with the long-incubation prion predominating. After a
couple of generations, however, the faster-acting prion grew dominant
(see "Adaptation and Selection..." in the bibliography).
researchers showed that two sections of aberrant prion killed mouse
nerve cells by disturbing the cell membrane (see "Neurotoxicity of..."
in the bibliography).
research into the inherited form of CJD shows that aberrant protein
causes massive apoptosis -- programmed cell death -- in the cerebellum
(see "Accumulation of Protease..." in the bibliography).
prospects for treating TSE seem to be improving. Knowing that prions
replicate in immune cells early in the disease could allow early treatment,
according to French neurovirologist Dominique Dormont. Drugs that affect
immune cells have improved survival among rodents experimentally infected
with scrapie or BSE (see "Prions: A Lone Killer... " in the bibliography).
However, Aiken cautions that veterinary drugs that slow the onset of
TSEs only work if used before symptoms appear, and the disease cannot
be detected at that stage.
We've stressed that neither BSE nor vCJD has been detected in the United
States. Before you sign off, read the "glass is half-empty" side of the
argument. And do check this photo
essay of a CJD victim.
gaining new respect for the infectivity of aberrant prions. A recent British
report indicated that a chunk of prion-laced meat as small as a peppercorn
could infect a cow -- and that thousands of British cows were infected
simply because cow feed was contaminated by pig feed while being handled
in grain mills.
at the University of Wisconsin-Madison, diagnosed dozens of cases of TSEs
among farmed mink in Wisconsin in the 1980s. When he learned that the
mink had been fed food prepared from "downer" cows -- cows that had died
for unspecified reasons. Marsh concluded that the most likely cause of
their illness was BSE among those cows.
Tom Pringle, who runs the Official
Mad Cow Disease Home Page, sees plenty of reasons for concern. "I'd
say it's just a matter of time before cases show up" in the United States,
he says, through one of three mechanisms:
infected while living in England or Europe.
medical products made from European-derived animal products.
home-grown eruption of BSE among U.S. herds, due either to contaminated
feed, or a spontaneous appearance of BSE.
By insisting that
the diseases have never been seen in the United States, Pringle adds,
the industry and government have set a high standard that will guarantee
panic if the diseases do appear.
But spread is the
order of the day: the day before The Why Files spoke with Pringle, the
London Sunday Times published a list of 70 countries that had received
contaminated animal products from Great Britain, and the list included
the United States. "In North America," Pringle says, the reaction among
regulators and industry "has basically been denial. I feel a very powerful
group has drawn a line in the sand -- just as the tide is about to come
And while the Centers
for Disease Control and Prevention does fund an effort to detect BSE and
vCJD, the budget is only $100,000, and the center receives only 40 percent
of the nation's cases of CJD -- which could allow victims of the human
version of mad cow to slip through the cracks.
We've not seen a guide to exactly what can carry CJD and what won't. However, prions mainly or entirely affect spine and brain tissue, and so the risk of eating whole cuts of meat, like steak, are far less than for hamburger, which is more likely to contain bits of tissue from central nervous system. There is no indication to date that milk is infectious.
One more reason
to fret. What about prion disease among elk and deer?