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Hard on the heals of the first U.S. “mad cow” discovery
comes a reassuring British report that cases of the human version
appear to have peaked and may fall dramatically short of early
projections. Tucked away in the verbiage is a tantalizing fact that
suggests the whole issue may prove to have been wildly overblown.
Initial projections from British scientists when the first
human cases surfaced in the mid-1990s indicated that literally
thousands of Brits would be dying of “variant” Creutzfeldt-Jakob
disease by now and that as many as half a million cases would
eventually develop, all because of widespread exposure to tainted
tissues from cattle with bovine spongiform encephalitis, so-called
“mad cow” disease. Statistics
published recently by the U.K. Department of Health, however, show
that only 139 deaths have occurred so far and that new cases are on
the decline. Deaths last year totaled 18, down from 28 as recently as
2000, and the most current figures project no more than 40 additional
cases over the next three-quarters of a century. As
tragic as any death is, far more people die each year of peanut
allergies. The
new numbers represent quite a statistical correction in such a short
timespan, especially given that the first researcher to propose a link
between vCJD and “mad cow” was still warning as recently as 2000
that “thousands of people” soon would be “going slowly and
painfully mad before dying.” What
happened? The
British government took quick steps to counter what was assumed to be
the mode of transmission, for one thing. The U.K. slaughtered tens of
thousands of cattle infected by or thought to have been exposed to BSE.
It also imposed a ban on all bovine brain and spinal cord material in
the human food chain, as well as any part of cattle more than 30
months of age. In addition, in an effort to stem further bovine
infections, the U.K. banned ruminant-derived products from feed, the
suspected vector between diseased animals and healthy ones. Other
factors may have been at work as well, however. The Department of
Health report notes — almost in passing — that every human victim
of vCJD so far shares a pre-existing, inherited genetic trait common
to only a little more than a third of the general population. The
trait is a mutation of a gene relating to “prions,” one form of
which is the infectious agent for BSE and other “spongiform
encephalopathies.” All vCJD victims to date have been found to
possess dual copies of the gene, meaning they inherited the mutation
from both parents. Scientists
by nature and training are loathe to issue statements without
equivocating baggage, so most studies and analyses of the vCJD-gene
link include a caveat warning that the trait in question may only
hasten incubation and that victims without the mutated gene may appear
in future years. That, of course, is pure speculation, whereas the
positive link is documented. The
mutation in question is also associated with the “sporadic” or
pre-BSE version of CJD, as well as similar rare prion-based diseases
such as kuru, and has even been linked to Alzheimers. No other
condition, however, has been found to occur exclusively among patients with dual copies of the gene. Such
exclusivity, in fact, is almost unheard-of in any medical condition
aside, perhaps, from the fact that no man has ever contracted ovarian
cancer or woman prostate cancer. Studies
in recent years have also shown that the overall infectivity of BSE is
much less than originally feared. Simply stated, it takes much more
infected material than originally assumed to transmit the infection to
another victim — “the dose makes the poison.” That means a few
stray prions lurking in a packing plant or tucked away in the bowels
of a feed mill that processed ruminant-derived meal at some point pose
a negligible threat. And
some researchers are even questioning the core assumption that “mad
cow” disease has anything whatsoever to do with vCJD. A
paper published in the British
Medical Journal edition of October 2001 evaluates the assumption
based on long-respected epidemiological criteria for establishing
cause and effect. It finds the BSE-vCJD “connection” lacking —
or nonexistent — in virtually every specific. The
paper is the work of Scottish surgeon Dr. George A. Venters, former Chairman of the British Medical Association's Public
Health Committee. Venters outlines the criteria that epidemiologists
use to evaluate evidence linking a given disease to its supposed
cause, then applies each of those criteria to the case of BSE and vCJD. In
some instances, he finds the evidence entirely lacking or notes that
it may not be available for years. “Strength of association” is
one example; there is no way to measure “details of individuals’
exposures” to infectious prions, for instance. Likewise, the
“dose-response relation” for humans is unknown.
“Reversibility” is another criterion, and Venters points out that
the assumed BSE-vCJD link “will be falsified” only “as and when
the disease occurs in people born after the bovine spongiform
encephalopathy prion has been eliminated from the human food
chain…” In
other words, if people continue to contract the disease after the
supposed cause no longer exists, the link will definitely be broken
— but that will take time. Meanwhile,
he assesses the other criteria, beginning with “biological
plausibility.” Venters points out that there is “no direct
evidence” that the BSE prion is infectious to humans, whereas
“there is evidence for a robust species barrier between humans and
prions from ungulate species.” For one thing, he notes, “Prions
produced in ungulates and humans have different sequences of amino
acids.” He adds that ingestion, the assumed mode of transmission, is
“an inefficient route” for prions aside from cannibalism — where
there is, obviously, no species barrier to overcome. Venter
thus concludes that “Infection of humans from eating the (BSE) prion
is therefore unlikely.” Another
criterion is “specificity.” Venter explains that “prion
infection differs from the conventional understanding of the
infectious process” in that “cells can only produce prion specific
to the species they belong to.” A
human E.coli infection, for instance, can be traced to contaminated
food because the same bacteria can be found in both the victim and the
tainted source. However, Venter points out, the BSE prion itself
“can never be detected in human brains or in any species other than
cattle.” Researchers
instead have attempted to link the bovine and human diseases through
similar damage to brain tissues, though that, too, is of limited value
because brain tissues themselves differ between species. Venter says
those who argue the connection are reduced at best to pointing out
“similarities” in “physico-chemical properties and strain typing
in laboratory experiments.” For
that reason, he concludes, “the specificity of the link between the
prion and the disease can only be inferred and remains an open
question. “Given
that it is impossible to prove that the (BSE) prion is infectious to
humans,” Venter continues, “evidence for the case has to be
indirect,” and this is where proponents of the theory may have
fallen victim from the beginning to wishful thinking or vested
interests. “The
evidence that has been amassed” so far, Venter chides, “is
directed towards confirming the hypothesis rather than testing it.”
In other words, those who promote the idea of such a link concentrate
their efforts on shoring up their position rather than challenging it
to see if it can stand on its own. Most
damning from an objective scientific perspective is Venter’s flat
assertion that “salient contrary information has been either played
down or ignored.” What
supposedly sets “new variant” CJD apart from the traditional
disease, for example, is the fact that it tends to strike young
victims whereas the conventional wisdom holds that the original
version strikes only in middle age or later. Venter points out,
however, that the first case of “traditional” CJD, described by
German researcher Creutzfeldt himself more than 80 years ago, was in a
23 year-old victim. So much for a “new” variant. The
idea that CJD is limited to older patients, in fact, didn’t become
popular until proposed decades later by the disease’s second
namesake, Jakob. To support his position, Jakob had to virtually
ignore Creutzfeldt’s pioneer case. Venter
adds — pointedly — that the paper claiming the existence of a
“new” disease and linking it to BSE also ignored Creutzfeldt’s
case and likewise ignored similarities between the “new variant”
of CJD and the South Pacific disease kuru, spread within a primitive
tribe by cannibalism. It cited kuru as a prion disease spread by
ingestion, Venter notes, but only as a way to support the idea that
“variant” CJD could be spread through food. Kuru
was thus cited where it was useful to the hypothesis, but “the
possibility of them being the same disease was not raised,” he says,
one example of “contrary information” being “either played down
or ignored.” He
cites several other examples in which “quality of evidence,” a key
criterion, is suspect, and concludes that evidence overall “is of
variable quality” and “seems to have been selectively developed”
along the lines of a fallacious “belief that multiple pieces of
suspect or weak evidence provide strong evidence when bundled
together.” So
why is BSE linked to vCJD? For
that, Venter turns to the “temporality” criterion, which
essentially ties the two diseases together by virtue of their timing. The
“new variant” was discovered shortly after the epidemic of BSE in
British cattle, Venter explains, so researchers attempted to link
them. Unfortunately,
he continues, “To prove that a disease is new, it is necessary to
review and legitimately reject other possibilities,” and this the
linkage proponents failed to do. Specifically,
he charges, they failed to rule out kuru and/or Creutzfeldt’s
original encephalopathy case. Venter notes “clinical and
neuropathological features” common to vCJD and kuru as well as to
the Creutzfeldt case. There are differences as well, he concedes, but
these “may be more of degree than of kind, in that survival of
patients with new variant Creutzfeldt-Jakob disease is likely to be
longer because they will generally have received better health care
than was available to people with kuru.” A
second element of “temporality” is what Venter terms the
“pattern of infection relative to exposure,” and he finds the link
weak here, as well. Venter
notes that all food-borne illnesses follow a common pattern or
“curve” in their distribution. “The shape of this curve holds
true for foodborne infections no matter whether the incubation period
is days,” as for E. coli, “or years, as is the case for prions,”
he insists. That curve would have followed the BSE infection rate in
cattle, he contends, if that were the source of vCJD. But
it doesn’t. Venter
notes that vCJD cases “have been appearing since 1994,” but that
“their rate of increase since then falls far short of what would be
expected if this was a foodborne infection.” Given
its weaknesses, he terms the “temporality” connection “at best
uncertain.” Venter
concludes with the observation that scientists have been trying to
draw boundaries around traditional or “sporadic” CJD ever since
Creutzfeldt’s first report more than eight decades ago, and those
boundaries have been repeatedly adjusted. He
accepts the idea that “variant” CJD is “a different disease”
from “sporadic” CJD, but questions “whether it is different from
kuru or from Creutzfeldt’s original case.” This, he says, remains
to be determined and will only be “clarified with the passage of
time.” Meanwhile,
Venter says, “I believe the evidence now casts serious doubt on the
case for a causal link between bovine spongiform encephalopathy and
‘new’ variant Creutzfeldt-Jakob disease,” adding that “The
medical profession should, at least, be publicly debating this as an
issue.” |
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