Mad cows, cannibalism and the shaking death

I made a brief appearance on
HuffPostLive on Wednesday, to talk
about kuru, a human form of mad
cow disease' that is transmitted by
eating infected nervous tissue. It was
for a segment of the broadcast
featuring cast members of We Are
What We Are , a new film about a
family of cannibals, one of whom
succumbs to the disease.
Kuru and other human forms of mad
cow disease are extremely rare
neurodegenerative conditions, but
they occasionally make the headlines
when new cases are found. The latest
case was reported earlier this month -
that of a New Hampshire man who
contracted variant Creutzfeldt-Jakob
disease (vCJD) via contaminated
neurosurgical instruments. The same
disease claimed the lives of 156
British people during the late 1990s,
all of whom had eaten infected beef.
Consequently, the European
Commission imposed a worldwide
ban on British beef, and the British
government ordered the culling of
hundreds of thousands of cows in
order to contain the disease.
Since then, no cases have arisen from
the consumption of infected beef.
Nevertheless, research suggests that
kuru, vCJD and other related diseases
could have incubation periods of at
least several decades, and perhaps up
to 50 years. Some researchers
therefore argue that many more
people may have been exposed to
infected beef in the UK during the 90s,
and that there may be a looming
epidemic of vCJD.
Read all about kuru, cannibalism and
vCJD in this article I wrote back in
Cannibalism and the shaking
death: A new form of the
disease and a possible epidemic
The film clip above shows several
victims of a disease called kuru. They
are – or rather were – members of
the South Fore, a tribe of
approximately 8,000 people who
inhabit the Okapa subdistrict of the
Eastern Highlands Province of Papua
New Guinea. In the 1950s and '60s, a
kuru epidemic swept through the
South Fore, claiming the lives of more
than 1,000 members of the tribe.
Later it was established that the
disease was transmitted by the tribe's
practice of ritualistic mortuary
The word kuru means "shaking
death" in the Fore language, and
describes the characteristic symptoms
of the disease. Because it affects
mainly the cerebellum, a part of the
brain involved in the co-ordination
of movement, the first symptoms to
manifest themselves in those infected
with the disease would typically be an
unsteady gait and tremors. As the
disease progresses, victims become
unable to stand or eat, and eventually
die between 6-12 months after the
symptoms first appear.
Kuru belongs to a class of progressive
neurodegenerative diseases called the
transmissible spongiform
encephalopathies (TSEs), which also
includes variant Creutzfeldt-Jakob
disease (vCJD) and bovine spongiform
encephalopathy (BSE, more popularly
known as mad cow disease). TSEs are
fatal and infectious; in humans, they
are relatively rare, and can arise
sporadically, by infection, or because
of genetic mutations. They are
unusual in that the infectious agent
which transmits the diseases is
believed to a misfolded protein.
(Hence, the TSEs are also referred to
as the prion diseases, "prion" being a
shortened form of the term
"proteinaceous infectious particle").
BSE first appeared in the UK in 1986.
A decade later, a young man from
Wiltshire who had eaten
contaminated beef became the first
victim of vCJD. Health officials
realized that the disease was
spreading among livestock because of
the practice of feeding them offal.
They warned that tens of thousands of
people could be at risk and
subsequently more than 200,000
cattle were culled in order to prevent
this, at a huge expense to the British
To date, though, only 156 people in
the UK, and a much smaller number
in other countries, have died from
vCJD. However, a longitudinal study
of the Fore people, published 2 years
ago, suggests that kuru and related
diseases may have an incubation
period of up to 50 years, leading
some researchers to argue that we
may yet face an epidemic of vCJD.
And last month, neurologists reported
a previously unidentified prion
disease which has killed 10 people in
the U.S. and infected 6 others.
The prion hypothesis was proposed by
Stanley Prusiner in 1982. It states
that TSEs are transmitted by an
abnormally folded form of the prion
protein. The normal form of this
protein is present in all cells, but its
function remains unknown. The
abnormal prion protein is insoluble
and prone to accumulate in clumps
which give the brain tissue a
characteristic sponge-like appearance
(spongiform encephalopathy means
"sponge-like brain disease"). The
clumps cause the shaking and
abnormal gait, because they make
cerebellar cells unable to properly
conduct nervous impulses.
It is now known that the clumps of
abnormally folded prion protein can
break down into smaller fragments.
Thus, if infected tissue is consumed,
these fragments act as " seeds ," which
cause the normal protein in the host
cells to adopt the abnormal
configuration and begin to
accumulate, in a process called a
nucleation-polymerization reaction.
The proposed structures of both forms
of prion proteins are shown in this
figure. The abnormal, pathogenic
form of the prion protein has a
higher proportion of structures called
beta-pleated sheets, and a lower
proportion of alpha-helices, than the
normal cellular form. The normal
form of the protein is thought to be
converted to the abnormal one by a
series of point mutations. Recent
evidence suggests that the abnormal
prion protein is not itself toxic
neurons, but rather that its
propagation generates a toxic by-
Experiments in yeast have implicated
heat shock proteins in the
propagation of the prion seed. Heat
shock proteins are a large family of
molecules present in all cells and in
all organisms. Their concentrations
are increased in response to elevated
temperatures, but they also act as
"chaperones" which assist newly-
synthesized proteins in assuming
their correct three-dimensional
structure, and prevent them from
clumping together. Thus heat shock
proteins are also involved in
disassembling the clumps of
abnormally folded prion proteins. In
yeast cells with a mutated form a
specific heat shock protein, the
clumps of prion protein are not
fragmented, and so are not passed on
during cell division.
Following the outbreak of kuru
among the Fore in the 1950s, cultural
anthropologists quickly established
that the disease was transmitted by
the practice of mortuary
cannibalism. When an individual
died, the female relatives were
responsible for dismembering the
body. They would remove the brain,
arms and feet, strip the muscle from
the limbs and open the chest and
abdomen to remove the internal
organs. Those that died of kuru were
highly regarded as sources of food,
because they had layers of fat which
resembled pork. It was primarily the
Fore women who took part in this
ritual. Often they would feed morsels
of brain to young children and
elderly relatives. Among the tribe, it
was, therefore, women, children and
the elderly who most often became
Although the Fore's cannibalism was
outlawed by Australian authorities in
the late 1950s, cases of kuru contined
to appear among members of the
tribe. This led John Collinge, head of
UCL's Department of
Neurodegenerative Disease , to travel
to Papua New Guinea to investigate.
Between 1996 and 2004, Collinge and
his team collected information about
the life histories of Fore tribesmen
and women, and during that time,
they identified 11 new cases of kuru.
Writing in The Lancet , Collinge
concluded that "the minimum
estimated incubation periods ranged
from 34 to 41 years… [but]
incubation periods of infection with
human prions can exceed 50 years,"
and subsequently reiterated the
possibility of a vCJD epidemic :
We must not forget that almost every
person in the UK was exposed to the
agent that causes variant CJD. It went
through the entire food chain, not just
in burgers but in cakes containing
gelatins made from meat products.
Even cosmetics contained beef-
derived chemicals then.
It is, however, possible that some
members of the Fore tribe continued
to practice cannibalism after it was
outlawed. This could explain the
cases that emerged during Collinge's
study, but does not necessarily
preclude a long incubation period for
kuru. It would, however, be very
difficult to determine how effectively
the law against cannibalism was
enforced by the Australians. It is
prudent to continue research into the
prion diseases, because it is possible
that we may face an epidemic of
vCJD. (A study published in 2007, also
led by Collinge, showed that prion
disease symptoms and pathology are
During their time with the Fore tribe,
Collinge and his colleagues collected
DNA samples from 10 of the 11 new
cases of kuru that had emerged.
Analysis of the samples showed that
the 10 individuals were all
homozygous for (i.e. had two
identical copies of) one particular
allele, or version, of the prion gene,
which may have made them
susceptible to infection. Similarly, the
156 British victims of vCJD could,
Collinge says, "represent a distinct
genetic subpopulation with unusually
short incubation periods for BSE."
The newly identified prion disease,
which has been named protease-
sensitive prionopathy (PSPr), was
reported by American physicians in
the Annals of Neurology. In the 11
cases, the average age of onset of the
disease was 62, and its duration, from
the appearance of symptoms to time
of death, ranged from 10 months and
5 years. Unlike most human prion
diseases, the loss of motor function
had been accompanied by cognitive
decline, and the post-mortems showed
a distinctive neuropathology.
Lead author Pierluigi Gambetti, head
of the National Prion Disease
Pathology Surveillance Center in
Ohio, believes that the disease has
probably "been around for many
years, unnoticed." PSPr differs from
other prion diseases in several ways.
The disease gets its name because the
prion protein isolated from the
victims, unlike that from other prion
diseases, was susceptible to
degradation by enzymes called
proteases. The abnormal prion
protein was also detected at
concentrations 16 times lower than
in other prion diseases.
Gambetti insists that the disease is
likely to caused by genetic and not
environmental factors, and that there
is no need for alarm. Significantly,
none of the 10 victims had mutations
in the prion gene, but several of them
had close relatives who had been
diagnosed with dementia. Thus, it
seems that a mutation or mutations
outside of the prion gene can
generate prion-like pathology. This is
the case in Alzheimer's disease, in
which there are mutations outside of
the gene encoding the amyloid
precursor protein. The new study
should lead to a better understanding
of the genetics of prion diseases, and
Gambetti is now carrying out
experiments in mice to determine
how the new disease is transmitted