##################### Bovine Spongiform Encephalopathy #####################
No sign of mad cow in 1997 cows
By Steve Mitchell
Published 4/15/2005 6:46 PM
WASHINGTON, April 15 (UPI) -- Two U.S. cows from 1997 that recent media
reports indicated might not have been properly screened for mad cow
disease were both tested multiple times and were found negative for the
deadly disease, United Press International learned in a two-year
investigation of the cases.
At the time both cases occurred, there was initial suspicion they might
be positive for mad cow disease -- also known as bovine spongiform
encephalopathy or BSE -- but the UPI investigation turned up documents
and witnesses that strongly indicated the cows were negative.
UPI decided not to publicize the cases due to documented evidence of the
negative test results and the strong opinion of several internationally
recognized BSE experts that the U.S. Department of Agriculture had
handled the cases appropriately and legitimately had ruled out mad cow
disease. Due to the attention the cases have received in recent media
reports, however, UPI is now publishing the information it has gathered.
In the first case, in May 1997, a cow with signs of a brain disorder
appeared at Oriskany Falls Packing Plant in Oriskany Falls, N.Y. At the
time, USDA inspectors, including agency veterinarian Masuo Doi, became
concerned the cow might have contracted BSE.
Subsequent tests detected no traces of the BSE pathogen, however, and
produced no indication the cow was infected, according to USDA documents
obtained by UPI via the Freedom of Information Act.
Top BSE experts reviewed the documents for UPI and all agreed the cow
looked negative and even commended the USDA's handling of the case.
In addition, a portion of the cow's brain was secretly transferred to
the National Institutes of Health, which independently tested the sample
and again found no evidence of BSE.
Another cow that appeared at the same packing plant in August 1997 was
tested using three different techniques and produced no indication it
had BSE or any similar disease, according to USDA testing records UPI
obtained via Freedom of Information Act requests.
Doi, who was involved in both cases, was not aware of the negative
results of the NIH test on the first cow until last February, when he
was informed by UPI. He then said he accepted that the animal did not
The Canadian Broadcasting Corporation, which aired television, radio and
print stories about the cases Tuesday, used clips of an interview
conducted with Doi before he was informed of the negative NIH test
results. The segment stated that Doi "says he is haunted by fears that
the right tests were not done and that his own department did not
properly investigate whether the cow had BSE."
The CBC story also referred to the Oriskany Falls plant as the
slaughterhouse that "eight years ago may have become the home of the
first American case of mad cow."
Felicia Nestor, a consultant to Public Citizen who was peripherally
involved in the two cases and featured in the CBC story, sent a letter
to CBC Producer Timothy Sawa on April 6 -- six days before the segment
went to air -- clarifying that she and Doi both had concluded it was
impossible to determine whether either cow had BSE.
Referring to "the possibility that either of the two cows had the
disease," Nestor wrote, "At this point, we think it impossible to draw
that conclusion," due to evidence to the contrary.
Nestor also expressed her concern that Sawa did not inform her during an
on-camera interview about the NIH negative test on the May cow or that a
test that came back positive on the August cow later was found to be
contaminated and invalid.
"From the evidence I am aware of at this point, it looks like these cows
were negative," Nestor told UPI. She added she is more concerned about
cows that were never tested for BSE than "anything about these cases."
Sawa and CBC Executive Producer Susanne Reber did not respond to UPI
requests for comment. From January through March 2005, a CBC crew
including Sawa collaborated with UPI on the mad cow investigation. UPI
subsequently withdrew from the collaboration.
Doi said Thursday he did not think the CBC stories accurately portrayed
his position on the cases. The context of the stories "kind of twisted"
my position, he said.
"I told Timothy (Sawa) you can't come up with presumptive conclusions
whether (the August cow) was negative or positive, you just have to
leave it as unknown," Doi added. "I don't think you have enough to say
that BSE is being covered up in the United States," he said.
The USDA rejected the assertion the cows were improperly tested for BSE.
Agency spokesman Jim Rogers told UPI he had contacted the CBC and
complained that their coverage of the cases omitted pertinent details
from the USDA documents indicating both cows had been extensively tested
and no trace of BSE was found.
"We showed them the documents ... they just chose to ignore it," Rogers
The May 1997 animal initially generated alarms internally at the USDA.
Pathologists at the agency's laboratory in Athens, Ga., observed
microscopic holes or spongiform changes in the brain tissue, which can
be an indication of mad cow. However, the Athens lab did not normally
conduct BSE tests and the holes were later determined to be in the wrong
region of the brain for BSE. The holes were in the white matter of the
brain, rather than the gray matter, where they typically occur when
caused by the mad cow pathogen.
Still, the agency rushed the brain samples to its National Veterinary
Services Laboratory in Ames, Iowa, which specializes in conducting BSE
tests. The USDA convened a panel of experts, including some from the
University of Iowa, who looked at the brain tissue and quickly concluded
it was obviously not BSE. Further tests conducted at Cornell University
indicated the cow had contracted a rare brain disease called progressive
The agency also ran two types of tests, called immunohistochemistry and
Western blot, that are used to detect prions, thought to be the pathogen
that causes mad cow. Neither test picked up any evidence of prions.
It does appear that a region of the brain known as the obex -- which is
preferred for testing for BSE because it is where prions typically
concentrate -- was missing from the tissue sample, but experts said it
still was possible to arrive at a solid conclusion the cow in this case
did not have BSE.
In addition, missing obex is not uncommon and happens probably in every
country that tests for BSE, according to Elizabeth Mumford, a
veterinarian and BSE expert at Safe Food Solutions in Bern, Switzerland,
a company that provides advice on reducing mad cow risk to industry and
Mumford said she would be more comfortable in the final diagnosis if the
obex had been tested, but added, "I still think it is likely a case of
governmental panic over an apparent something that really did turn out
to be nothing."
Doi sent the secret tissue sample to Joe Gibbs, the head of the NIH's
Laboratory for Central Nervous System Studies, a now-defunct lab that
had been conducted groundbreaking work on made cow and similar disorders
Bruce Johnson, a former NIH scientist who conducted the test on the
sample, said he remembered the case.
"That was a negative cow," Johnson told UPI, noting he tested at least
three different samples from the brain tissue using the Western blot
method. "It was clearly negative," he said.
Johnson said he did not know whether the cow's obex was included in the
samples he tested, but noted he had worked extensively with mad cow-like
diseases at the NIH in humans and a variety of animal species. Based on
the cow's advanced symptoms, he said, if the cow had been infected with
BSE, he likely would have detected prions in other regions of the brain.
Johnson also said he knew Joe Gibbs quite well and felt certain if Gibbs
had thought for a moment the cow was positive, he would have published
an urgent paper about it in a scientific journal, because it would have
been the first case of mad cow disease in the United States.
Several mad cow testing experts reviewed the records from the first case
for UPI and all agreed the USDA acted properly.
"It seems to me that USDA went above and beyond the book in dealing with
this case, and legitimately ruled out BSE," said one of the BSE experts,
who requested anonymity. The expert, who works at one of the most
respected BSE labs in the world, added, "They handled it very well."
Stephen Dealler, a medical microbiologist at Britain's Lancaster Royal
infirmary, who has been researching BSE since it first appeared in the
United Kingdom in the 1980s, told UPI, "I have had a look and what it
shows to me so far is that they (the USDA) have tried quite hard and
were extremely worried at the time ... but have got good reasons to say
that no BSE was found."
Dealler jokingly said he was embarrassed he could not find much to
criticize the agency for, because he had developed a reputation of being
a bulldog on BSE.
"I am very confident that the proper diagnosis has been made," said a
veterinary pathologist specializing in the diagnosis of neurological
diseases and transmissible spongiform encephalopathies, or TSEs, who
works at another of the premiere BSE testing labs in the world. The
source also requested confidentiality.
"I think they did enough to rule out BSE in this case," the pathologist
In the August 1997 case, another cow with neurological symptoms appeared
at Oriskany Falls. This time, Doi obtained cerebrospinal fluid from the
animal and sent it to Joe Gibbs. Gibbs tested the sample using a
patented procedure he was developing for diagnosing a disorder similar
to mad cow disease that occurs in humans. The CSF test came back
positive, but the sample contained blood, which would cause the test to
turn positive whether the animal was infected with mad cow or not.
It is unclear whether Gibbs, who is now deceased, understood the
ramifications of blood contamination or just wanted to double-check the
status of the cow, but he called Linda Detwiler, a veterinarian and head
of the USDA's BSE surveillance program at the time, and asked her to
look into the matter.
The cow's brain already had been screened using immunohistochemistry --
the normal screening method used for BSE suspects -- and it was
negative, but to make sure nothing had been overlooked, Detwiler asked
the USDA lab to run the Western blot, which also found nothing to
A report in USDA's testing records notes that a histopathological
examination -- a rudimentary test not considered reliable for excluding
mad cow cases -- was "of questionable validity because it is unknown
whether" the tissue being examined included the obex region.
The report went on to state, however, the examination "revealed no
combination of lesions, which is consistent with any transmissible
spongiform encephalopathy, including (BSE)."
Based on these examinations, the lab concluded, "No evidence of
infection by any agent which is known to cause a transmissible
spongiform encephalopathy was found."
Mumford reviewed the records of the case for UPI and said, "I think
actually they did a good job."
She said her colleagues in Switzerland also had looked at the documents
and they agreed there was nothing to indicate this cow might have been
positive. "There's no alarm bells ringing over on this side of pond,"
Detwiler, who is now retired from the USDA, but is still respected by
BSE experts and has a reputation for being forthright, told UPI, "I
didn't have any doubt then or now that it wasn't BSE."
Steve Mitchell is UPI's Medical Correspondent. E-mail: firstname.lastname@example.org
Copyright © 2001-2005 United Press International
> "That was a negative cow," Johnson told UPI, noting he tested at least
> three different samples from the brain tissue using the Western blot
> method. "It was clearly negative," he said.
just what i said, they used WB in 1997, but NOT in 2004 on those
positive, positive, inconclusives. WHY was this? WHY will USDA
not comment and not retest those brains that were so suspicious in
i will tell you why, the same damn reason they rendered that other
mad cow in Texas without testing at ALL, they simply knew what they
had and did not want to find and document it...
and for those that do not think USA is covering up mad cow
disease now and in the past, well, dream on...
Q&A Dr. Jean-Philippe Deslys 1. What is the standard regime for testing
of suspect animals in the EU? The regime is an initial screening by a
high-output test, the Bio-Rad test. If a result raises suspicion, a
confirmatory test is conducted with the Western blot test. 2. How long
has this been the case? Its a fairly recent development. Only recently
has the Western blot test become sensitive enough, with the addition of
phospohtungstic acid precipitation step. The Bio-Rad test (which Deslys
helped develop) is extremely sensitive, and the standard Western blot is
extremely reliable with high-signal test results. However, it had to be
made more sensitive for low-signal (samples with low density of
malformed prions) samples. It has been made more sensitive.
Reproducibility is the problem with the IHC test. It is not
standardized; depending on the lab and its protocols, or even on the
technician involved in the test, one can get conflicting results. 3. Is
there a way to measure the three tests in sensitivity, accuracy and
objectivity? Historically, yes. The IHC was the gold standard at one
point, but we have shifted to the Western blot. It requires less work,
it is more sensitive and its results are reproducible. IHC relies on
localization. If you have a weak signal case, you may get lucky and test
a spot with a high concentration of prions. But the opposite it true
too; you can miss an infection by testing a sample with low
concentrations. Western blot is much better for low signal situations.
4. The USDA in 2003 used the Western blot to confirm the BSE case in
Washington state, and it sent samples to the U.K. for independent
testing. In the case this November, which it announced was negative, it
instead used the IHC test and did not send samples to the U.K. Is this
good science? Its not logical. If you have two consecutive questionable
screenings, you do another test. I can only advise, its managements
duty at USDA to make the decisions. But when you have a discrepancy
between the rapid test and the IHC, it is only logical to confirm it
with another test. 5. We are hearing now about a new strain of BSE,
atypical BSE or aBSE. Or BaSE. We have heard that IHC, the so-called
gold standard, cannot detect the variant. Is this true? Yes. There have
been a few cases, one in Italy, one in Belgium, one here in France. It
seems to only affect very old animals. The distribution in the brain is
very different than we see with BSE, it looks very different. The IHC
test will come back negative. This his a very recent phenomenon. I have
no opinion on its virulence. We do not know where it comes from. It
could be a version of sporadic infection. Western blot caught them, but
we would not even know it existed if we werent running systematic
testing in the EU. BSE was around for a long time before we caught it
and by then, it was everywhere. It had become highly infectious. It
probably amplified due to low-temperature rendering. The disease was
recycled through the food chain, and was given time to amplify. By the
time it was identified, even good cooking couldnt eliminate it. I cant
stress enough that systematic testing is necessary. Withdrawing all
positives from the food chain is the best way to break the cycle. What
can happen with testing of only cattle that are clearly at risk is that
several can remain undetected. Canada has tested about 30,000 head of
cattle and has three positives. That would indicate that there are
probably undiscovered cases. And what happens then is that the disease
is allowed to amplify. You have to maintain testing. When people choose
to protect their economic interests over public health, it can have a
boomerang effect. It happened all through Europe. They always deny; its
not OUR problem, it is our neighbors problem. And then a single case is
discovered and the public reacts. The economic results are devastating.
It would be better to just assume BSE is present and use systematic
testing as protection. That way, the public is reassured that it is not
entering the food supply. By systematic testing, I mean doing as we do
in the EU, which is to test every animal over 30 months of age when it
is slaughtered. In Europe, three times as many cases of BSE have been
caught by systematic testing as by clinical testing (of clearly sick
animals). In 2004, eight clinical cases were discovered, 29 were
discovered at rendering plants, and 17 at slaughter. We should be using
these tests as a weapon to protect the public and to give them assurance
that the food supply is being protected.... snip ...END Dr.
Jean-Philippe Deslys, Head, Prions Research Group, Atomic Energy
Commission, France Q&A Prof. Adriano Aguzzi Dear Mr. Singeltary I
sympathize with your wish to have the most sensitive assay implemented.
However, the situation is not as simple as one might think. In the case
of homogeneously distributed agent, biochemical detection of PrPSc is
indeed likely to be more sensitive than immunohistochemistry. In the
case of variegated, punctate distribution of the agent, morphological
methods may indeed be an asset. There are also issues of feasibility. In
my laboratory, we routinely run phosphotungstic acid precipitation
followed by Western blotting. However, this is an extraordinarily
cumbersome procedure. The sensitivity is increased vastly, but the
amount of work needed is also amazing. There is no way I could see our
own procedure implemented for mass screening of millions of cows -
unless one would draft a veritable army of laboratory technicians. For
all these reasons, while I see all your points, I feel unable to offer a
strong public opinion in favor or against any specific methods. The
final decision needs to take into account a variety of complex factors,
and that is why I believe that it is best left to a panel of experts
rather than to a public discussion. Best regards Adriano Aguzzi
____________________________ Prof. Adriano Aguzzi (MD PhD hc FRCP
FRCPath) Institute of Neuropathology, University Hospital of Zürich
Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland Tel. ++41-1-255 2107
Tel. (direct line): 2869 Fax: ++41-1-255 4402, cellular: +41-79-320 1516
=========================================== PNAS | March 1, 2005 | vol.
102 | no. 9 | 3501-3506 NEUROSCIENCE Diagnosis of human prion disease
Jiri G. Safar *, , Michael D. Geschwind , Camille Deering *, Svetlana
Didorenko *, Mamta Sattavat Â¶, Henry Sanchez Â¶, Ana Serban *, Martin
Vey ||, Henry Baron **, Kurt Giles *, , Bruce L. Miller , Stephen J.
DeArmond *, Â¶ and Stanley B. Prusiner * *Institute for
Neurodegenerative Diseases, Memory and Aging Center, and Departments of
Neurology, Â¶Pathology, and Biochemistry and Biophysics, University of
California, San Francisco, CA 94143; ||ZLB Behring, 35041 Marburg,
Germany; and **ZLB Behring, 75601 Paris, France Contributed by Stanley
B. Prusiner, December 22, 2004 AB Abstract With the discovery of the
prion protein (PrP), immunodiagnostic procedures were applied to
diagnose Creutzfeldtâ¬Jakob disease (CJD). Before development of the
conformation-dependent immunoassay (CDI), all immunoassays for the
disease-causing PrP isoform (PrPSc) used limited proteolysis to digest
the precursor cellular PrP (PrPC). Because the CDI is the only
immunoassay that measures both the protease-resistant and
protease-sensitive forms of PrPSc, we used the CDI to diagnose human
prion disease. The CDI gave a positive signal for PrPSc in all 10â¬24
brain regions (100%) examined from 28 CJD patients. A subset of 18 brain
regions from 8 patients with sporadic CJD (sCJD) was examined by
histology, immunohistochemistry (IHC), and the CDI. Three of the 18
regions (17%) were consistently positive by histology and 4 of 18 (22%)
by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all
18 regions (100%) for all 8 sCJD patients. In both gray and white
matter, 90% of the total PrPSc was protease-sensitive and, thus, would
have been degraded by procedures using proteases to eliminate PrPC. Our
findings argue that the CDI should be used to establish or rule out the
diagnosis of prion disease when a small number of samples is available
as is the case with brain biopsy. Moreover, IHC should not be used as
the standard against which all other immunodiagnostic techniques are
compared because an immunoassay, such as the CDI, is substantially more
sensitive... snip... Discussion snip... The studies reported here are
likely to change profoundly the approach to the diagnosis of prion
disease in both humans and livestock (31 33). The superior performance
of the CDI in diagnosing prion disease compared to routine
neuropathologic examination and IHC demands that the CDI be used in
future diagnostic evaluations of prion disease. Prion disease can no
longer be ruled out by routine histology or IHC. Moreover, the use of
IHC to confirm cases of bovine spongiform encephalopathy after detection
of bovine PrPSc by the CDI (10) seems an untenable approach in the
future. Clearly, the CDI for HuPrPSc is as sensitive or more sensitive
than bioassays in Tg(MHu2M) mice (Fig. 1). Our results suggest that
using the CDI to test large numbers of samples for human prions might
alter the epidemiology of prion diseases. At present, there is limited
data on the frequency of subclinical variant CJD infections in the U.K.
population (34). Because appendixes and tonsils were evaluated only by
IHC, many cases might have escaped detection (Tables 1 and 2). Equally
important may be the use of CDI-like tests to diagnose other
neurodegenerative disorders, such as Alzheimer's disease, Parkinson's
disease, and the frontotemporal dementias. Whether IHC underestimates
the incidence of one or more of these common degenerative diseases is
unknown. Moreover, CDI-like tests may help determine the frequency with
which these disorders and the prion diseases occurs concomitantly in a
single patient (35, 36).
http://www.pnas.org/cgi/content/abstract/102/9/3501 Dr. Dehaven, this
brings me back to those other TEXAS cows, those at the Purina Gonzales
feed mill. FDA stated ; > FOR IMMEDIATE RELEASE P01-05 January 30, 2001
snip... > FDA has determined that each animal could have consumed, at
most and > in total, five-and-one-half grams - approximately a quarter
ounce -- > of prohibited material. These animals weigh approximately 600
pounds. > snip... > It is important to note that the prohibited material
was domestic in > origin (therefore not likely to contain infected
material because > there is no evidence of BSE in U.S. cattle), fed at a
very low level, > and fed only once. The potential risk of BSE to such
cattle is > therefore exceedingly low, even if the feed were
contaminated. > snip...
http://www.fda.gov/bbs/topics/NEWS/2001/NEW00752.html Subject: 1 in 2
CHANCE OF GETTING BSE AKA MAD COW BY THE ORAL ROUTE (PRIMATE STUDY)
Date: January 27, 2005 at 7:03 am PST Risk of oral infection with bovine
spongiform encephalopathy agent in primates Corinne Ida Lasmézas,
Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm
Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray,
Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The
uncertain extent of human exposure to bovine spongiform encephalopathy
(BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is
compounded by incomplete knowledge about the efficiency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to
non-human primates. We gave two macaques a 5 g oral dose of brain
homogenate from a BSE-infected cow. One macaque developed vCJD-like
neurological disease 60 months after exposure, whereas the other
remained free of disease at 76 months. On the basis of these findings
and data from other studies, we made a preliminary estimate of the food
exposure risk for man, which provides additional assurance that existing
public health measures can prevent transmission of BSE to man. Published
online January 27, 2005 http://www.thelancet.com/journal/journal.isa or
BSE/TSE .1 GRAM LETHAL NEW STUDY SAYS via W.H.O. Dr Maura Ricketts [BBC
radio 4 FARM news] (audio realplayer LISTEN)
http://www.maddeer.org/audio/BBC4farmingtoday2_1_03.ram THE ONE THAT GOT
AWAY Statement on Texas Cow With Central Nervous System Symptoms
horizonal rule FDA Statement FOR IMMEDIATE RELEASE Statement May 4, 2004
Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA Statement
on Texas Cow With Central Nervous System Symptoms On Friday, April 30 th
, the Food and Drug Administration learned that a cow with central
nervous system symptoms had been killed and shipped to a processor for
rendering into animal protein for use in animal feed. FDA, which is
responsible for the safety of animal feed, immediately began an
investigation. On Friday and throughout the weekend, FDA investigators
inspected the slaughterhouse, the rendering facility, the farm where the
animal came from, and the processor that initially received the cow from
the slaughterhouse. FDA's investigation showed that the animal in
question had already been rendered into "meat and bone meal" (a type of
protein animal feed). Over the weekend FDA was able to track down all
the implicated material. That material is being held by the firm, which
is cooperating fully with FDA. Cattle with central nervous system
symptoms are of particular interest because cattle with bovine
spongiform encephalopathy or BSE, also known as "mad cow disease," can
exhibit such symptoms. In this case, there is no way now to test for
BSE. But even if the cow had BSE, FDA's animal feed rule would prohibit
the feeding of its rendered protein to other ruminant animals (e.g.,
cows, goats, sheep, bison). snip...
http://www.fda.gov/bbs/topics/news/2004/NEW01061.html What GAO Found
United States Government Accountability Office Why GAO Did This Study
Highlights Accountability Integrity Reliability
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