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PRIONS
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Proteins have helically coiled sections,
much like a telephone cord. They tangle
to form complex, three-dimensional
shapes that allow them to perform their
functions. When improper folding causes
certain proteins to take on the wrong
shape, as happens to prions, the
molecules can become pathogenic.
Prionsprotein molecules that can take on
a misshapen, pathogenic formare among the
strangest foodborne causes of disease yet discovered.
For many years, prions filled a highly exotic
and arcane corner of biological research, and their
uniqueness led to tremendous scientific excitement,
as well as two Nobel prizes. Despite this
attention, the curious molecules remained mostly
unknown except to specialists because they had
little relevance to the world at large.
That all changed in 1986 with the sudden
emergence of mad cow disease, or bovine spongiform
encephalopathy (BSE), first in Great Britain
and, later, in other parts of the world. Hundreds
of thousands of cows eventually became infected.
A decade afterward, health officials began seeing
a similar disease in people who had eaten infected
beef. After dwelling for so long in near-obscurity,
prions abruptly morphed into a hot topic for both
the media and politicians.
Protein molecules, the basis of prions, make up
the normal cellular machinery of living organisms.
After each long protein molecule is produced, it
undergoes a process called protein folding, in
which it kinks into a characteristic shape, or conformation,
which determines how it works. Although
the analogy is imperfect, you can think of proteins
as mechanical devices such as gears. The conformation
of the folded protein, like the type of gear,
determines what it does and how other proteins may
interact with it (see Prion Diseases, page 158).
The idea that prion proteins can cause disease
simply by shifting their normal three-dimensional
conformation to an alternative, abnormal shape
was highly controversial for many years. All other
cases of microbial infection required an information
molecule, such as DNA or RNA, to transmit
building instructions for the pathogen. Prions, on
the other hand, are more akin to a poison that
spreads; apparently, only a single protein molecule
is enough to start the chemical “infection.”
After many years of pursuing the topic and
countering critics, Stanley Prusiner of the University
of California, San Francisco, won the 1997 Nobel
Prize in Physiology or Medicine for this discovery.
His prion theory of disease is now widely accepted.
Yet many mysteries remain about the class of
prion-associated diseases known as transmissible
spongiform encephalopathies. As of this writing,
for example, no one has yet deduced the purpose
of prions in their normal conformation, although
some scientists believe the proteins may play a role
in cellular communication. Details about exactly
how and why the abnormal conformation causes
disease are also lacking.
Despite this dearth of knowledge, an ominous
pattern exists. All prion diseases known to date
affect the nervous system, primarily brain tissue,
where the misfolded proteins tend to clump
together and leave tissue damaged and sponge-like
in appearance. Normally, the brain is protected
from incoming proteins and other large molecules
by the blood–brain barrier, but the prions somehow
manage to breach that blockade. Some
researchers suspect that the brain disease may
progress (albeit slowly) because nerve cells are not
replaced the way other body cells are, although
research has yet to explain clearly why symptoms
do not appear elsewhere in the body.
In the absence of solid information, several
myths have sprung up about prions. Many people
order their beef well-done out of concern over mad
cow disease, for example. Unfortunately, that is
a pointless precaution because no reasonable
amount of heat will destroy the incredibly stable
prions. Autoclaves that operate at 121 °C / 250 °F,
typically used to sterilize scientific equipment,
seem to have little effect on the unique proteins,
even after treatment for 48 hours. Likewise, the
U.K. government cremated infected cows to
contain the disease, only to discover that their
ashes still harbored prion proteins.
Chemicals are ineffective as well, and prions
easily resist exposure to both ultraviolet and
ionizing radiation. Even acid treatments have not
worked well; the concentration required to destroy
prions also dissolves stainless steel. Researchers
recently discovered that a common soil mineral can
degrade prions and are still hoping to develop
disinfectants and, eventually, therapeutic drugs for
prion diseases, but as of mid-2010, no good method
has been developed for inactivating or destroying
prions in meat that is bound for the dinner table.
From Sheep to Beef to People
The discovery of prions emerged from research
into scrapie, a degenerative brain infection that is
inevitably fatal to sheep and goats. The disease was
formally recognized by science in 1738it has
probably been around far longerbut only
recently recognized as a prion-related illness.
Scrapie essentially dissolves the brains of
affected sheep and goats before ultimately killing
them. Scientists have not yet determined how
scrapie passes among the animals, but some
suggest that it may be transmitted when sheep
eat grass contaminated with the blood of other
sheepfor example, from the placenta remaining
after delivery of a lamb by a sick ewe.
An experiment with scrapie-infected sheep in
Iceland only deepened the mystery. Icelanders
slaughtered entire flocks to eliminate the disease,
and they left pastures that the sick sheep had
grazed fallow for several years. When healthy
sheep that the farmers knew to be scrapie-free
were introduced to those pastures, they still
contracted the diseasethough no one could say
where the prions infecting them had originated.
One of the great ironies about the intense media
attention paid to mad cow disease is that “mad
sheep” disease has been documented since the
18th century with little fanfareprobably because
physicians have never noticed any scrapie-like
illness in humans who ate lamb, mutton, or sheep
brains. This species barrier suggests that scrapie
prions in sheep cannot convert human proteins to
the disease-causing conformation. Presumably,
human proteins are too different for the scrapie
proteins to exert their twisted influence.
Humans have their own scrapie-like diseases,
however, including several forms of Creutzfeldt-
Jakob disease (CJD), which was named after the
two German neuropathologists who first reported
it in the early 1920s. These very rare diseases affect
about 200 people annually in the United States;
the prevalence worldwide is about one in a million.
An inherited version of CJD and a related
disease, fatal familial insomnia, have a clear genetic
basis, but hereditary CJD is thought to account for
only 5%–10% of cases in the U.S. By far the most
common form is “sporadic” CJD, or sCJD, whose
victims have no known risk factors. Sporadic CJD
appears to result from an accidental or spontaneous
shift in normal prion proteins, although
extensive research has not yet shown any pattern.
No treatment for CJD exists; it is always fatal.
Symptoms include dementia that progresses much
faster than what is typical for Alzheimer’s disease,
often accompanied by impaired muscular coordination,
vision, memory, and judgment, as well as
personality changes. The disease can incubate for
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MICROBIOLOGY FOR COOKS 157