Prion disease: May 99 News
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Official USDA estimate of BSE in downer cows
The USDA's secret scrapie non-survey
Hunkering down in the APHIS BSE Situation Room
FDA Warns About Dialysis Blood
Tainted hormone-free beef dispute heats up
Eugene, Oregon CJD cluster
CWD in Oregon: worried hunters
CWD trophies -- a worry for taxidermists?
CWD in Arkansas?: no IHC testing
Nonsensical bacteria proposal funded
EU's Fischler asks US to analyse science in beef row
20 cases of BSE on organic farms: chicken manure?

Official USDA estimate of BSE in downer cows

18 May 99  USDA reports, listserve correspondence, webmaster opinion
[East Coast groups petitioning the federal government for more of a ban on animal to animal offal feeding acquired a 7.5 kilogram stack of USDA internal documents under the Freedom of Information Act. The webmaster agreed to review these for science and policy news on the condition that documents of interest could be retained and posted to the Internet.

Perhaps half a pound of these document contained newsworthy items. Most of the documents are mind-numbing reminders of the ability of civil service to generate insipid vapidity. The worst offenders are at the embassies and the Foreign Agricultural Service. The petitions themselves and web links for the groups are posted on this site.

The secret documents reviewed here are not found on the USDA or APHIS web pages. They should be: these publications represent the best available official USDA data on the incidence of BSE in downer dairy cows in the United States. Comments by agency scientists during the week of 12 May 99 have been incorporated in the final account below.

Downer cows are described in agency jargon as "nonambulatory" animals. These animals have a wide variety of underlying medical problems not attributable to BSE, resulting in the cow not being able to stand. -- webmaster]

Dr. Mark M. Robinson, in the mid 90's a laboratory scientist at ARS, USDA, Animal Disease Research Unit, Pullman, Washington, investigated the Stetsonville mink episode. Robinson had published several papers on experimental transmission to cattle and sheep, concluding like everyone else that the data best fit Marsh's inference of a very low level of a non-UK strain of bovine spongiform encephalopathy in Wisconsin dairy cattle in the mid-80's.

In the FOIA documents summarized here (obtained by the Center for Food Safety), Robinson focused on quantitative estimates of the incidence of US-BSE under various assumptions (eg, all the US mink outbreaks were cattle-based, mink always acquired TME upon exposure to a single BSE cow, that TME was always reported to authorities, mink operations use of downer cows were constant over time), based on interviews about practices with local mink farmers, slaughterhouse operators and renderers, and state agricultural statistics about the number of mink farms and downer dairy cattle. This was published in the Proceedings of the Sixth International Workshop on BSE, Kingsmill Resort, Williamsburg, Virginia, 27 Feb 95, a year before nvCJD was announced.

Robinson concluded that "at most 1 out of every 27,500 nonambulatory adult cattle [downers] was affected with the transmissible encephalopathy, and 1 out of 975,000 of all adult cattle was affected with the transmissible encephalopathy per year in in Wisconsin."

The first number says the USDA testing program to date is woefully inadequate: what is learned from testing 7,500 downer cows if the agency own scientists think the incidence is 1 in 27,500?

The second number agrees well with the one in a million figure for familial BSE based on independent molecular biology considerations (Gibbs' Principle). A Swiss cow was recently found with 7 repeats in its prion gene, partly validating this argument. The annual slaughter in the US is roughly 36,000,000 cattle; using the USDA number of 1 in 975,000 gives an agency estimate of 36.9 infectious animals a year entering the food chain. TME outbreaks have occured all over the world -- it would not be surprising if other countries had similar incidence statistics; Robinson is thus not singling out US agricultural practices for criticism.

Quotes and methodological considerations from this paper:

"Similar studies [oral inoculation of mink and cattle with sheep scrapie] over more than 20 years have been uniformly unsuccessful, suggesting that the scrapie agent does not cause TME."

Tables 1-4 describe various transmission experiments completed or in progress. Table 1 describes 3 strains of mink TME tested in cattle, Table 2 describes 6 isolates of scrapie tested in cattle; Table 3 describes 7 isolates of scrapie tested in mink; Table 4 describes 3 isolates of UK-BSE tested in mink.

An import certificate signed by GAH Wells of Britain's Central Veterinary Office establishes that this was genuine BSE imported from the Central Veterinary Laboratory to Pullman, Washington. What might be called bovine spongiform encephalopathy has thus been observed in experimental US cattle inoculated with US scrapie strains at several facilities and what is commonly taken to be a mink-passaged US strain of BSE (Table 1). The mink in table 3 and lab mice elsewhere represent US animals infected with UK-BSE. These experimental animals did not enter the food chain no escape to the wild; there are no reports of horizontal transmission to animals that subsequently used the facilities and pastures, as is seen in scrapie and CWD but not TME.

"The survey of mink feeding practices revealed that the use of nonambulatory cattle in mink feed has been a constant feature of some mink operations in Wisconsin for many years. Specifically, 18% of the survey respondents reported current and/or historical use of adult nonambulatory cattle in their mink rations over a period of 223 ranch-years without incidence of TME. Also, the survey results indicated that mink ranchers used an historical average of approximately 5% or the nonambulatory cattle available each year."

Related documents: page 15 from the recent Foreign Animal Disease Report, Number 22-5, Fall 1995. This provides a map showing state-by-state origins of the 2,291 submissions for BSE testing (all reported negative, methods not described, IHC probably with weak rabbit polyclonal antibody) 1986-June, 1995. Cattle brains numbered 551 from Texas, 305 from California, 229 from Pennsylvannia, 161 from Wisconsin, 118 from North Dakota, ...

An earlier team-written document entitled, "Bovine Spongiform Encephalopathy in the United States, July 1993", published by USDA APHIS VS CEAH Ft. Collins contains an even more detailed account on pages 21-25. The abstract states, "the survey suggested that almost 5,000 nonambulatory cows suspected of having a transmissible spongiform encephalopathy (TSE) could have been fed to mink in the surveyed States in 1992."

Figure 1 shows the disposition of culled downer cows: on-farm disposal, custom slaughter, sale to mink farm, state or federal slaughter plant, or direct to renderer. "The greatest number of nonambulatory cows are believed to go to rendering. Rendering facilities do not maintain records on numbers and causes of nonambulatory cows... acquisitions are made by drivers who are not trained nor charged with responsibility to assess reasons for moribundity."

"The annual incidence of nonabulatory cows was 21.4 per 1000 cow-years at risk, in dairy herds participating in the Dairy Herd Improvement Association in Minnesota in 1983....A prospective study of 34 dairy herds in New York revealed that 28 nonambulatory cow cases occurred out of 7,763 lactations (4,092 animals) during a 4-year period, or 3.6 per 1000 cow-years at risk."

"The only available data on nonambulatory cows from State [slaguhter] plants came from Wisconsin, which has the largest number of milk cows in the US [California is now larger -- webmaster] and has four State-inspected plants specifically for nonambulatory cows. In 1992, these four plants slaughtered a total of about 10,000 nonambulatory cows."

The 7 states surveyed were Wisconsin, New York, Pennsylvania, Minnesota, Idaho, Utah, and Washington, with 81% response rate (18 of 21, 51 herds). "Responding veterinarians reported 363 nonambulatory cows out of 13, 429 cows on the 51 premises for 1990-92, for an incidence of 27 per 1000 cow-years at -risk.

Table 1 shows 52.5% of the downer cows going direct to a local renderer (average distance 25 miles) and 6.3% going to mink producers (there are 2,000 in the US).

"Because mink producers pay a premium for nonambulatory cows, it appears reasonabble that the practice of feeding nonambulatory cows could occur wherever both large numbers of dairy cows and mink are found. As mainy as 2,157 nonambulatory cows [excludes slaughter plants] per million milk cows, or a total of 8=9,482 nonambulatory cows, could have been fed to mink in the 7 surveyed States in 1992. Based on the sample response, only half of those cows would have had an idenfiiable reason [one that excluded TSE] for being nonambulatory. This equates to an estimated 4,741 nonambulatory cows that were, hypothetically, a potential source of TSE in the surveyed States."

The 5 reported outbreaks of TME; during the last 50 years give one outbreak per 20,000 mink farm-years; extrapolating from this study, a number of 66,374 downer cows were fed to mink from the 7 surveyed states since the last acknowledged TME outbreak in 1985. Half of them had no conventional medical explanation for being downers. "Given this large number of nonambnulatory cows fed to mink, the historic and current mink population, and the infrequent occurrence of TME, if TSE exists in cattle in the US, it must be very rare or transmissible to mink only under very unusual conditions."

The USDA should be credited for publishing Robinson's paper and the CEAH study in a timely manner. There is no coverup here, just a need to have the documents more accessible on their web site. Educational outreach is an acknowledged agency mission.

These are apparently their best available in-house studies of the incidence of non-UK BSE in the United States. Both studies include many properly cautionary statements and draw only provisional conclusions because of necessary assumptions and incomplete data underlying the studies.

Robinson dropped out of TSE research shortly after this report, resurfacing at a seemingly unrelated desk job in Vienna, Austria with the International Atomic Energy Agency, an odd move for a career-track TSE experimentalist that fueled a great deal of speculation in view of the orchestrated harassment of University of Wisconsin researcher RF Marsh.

However, Mark Robinson responded promptly to a webmaster email query on 18 May 99 to add clarifying comments (assimilated into the final account above) on his research. Robinson states that his move from the USDA-Agricultural Research Service to the FAO/IAEA Food and Agriculture Program at the International Atomic Energy Agency was associated with personal interests and a one-year sabbatical by the USAD-ARS to work with the IAEA, which he then extended. However, he is returning shortly to the USDA-ARS by prearrangement.

Robinson made two important comments: First, the CEAH paper cited above was an group effort from USDA-APHIS that he had no hand in writing. Second he says that working with scrapie/BSE/TME/CWD had become a political chore that was devoid of science and that he chose to leave the arena when nvCJD was announced publicly in March 1996.

His current position is as the head of a laboratory group concerned with animal disease diagnostic technologies that are useful for veterinary laboratories in developing countries. (Atomic Energy somehow takes in FAO, see below) He is of the opinion that the animal and public health concern over BSE pales in comparison to the disease problems of rinderpest, trypanosomosis, brucellosis, foot-and-mouth disease, african swine fever, rift valley fever, tick-borne diseases, etc. He may return to TSEs in the future, but there are "many other approachable animal disease problems that need attention as well."

Mark M. Robinson, PhD, DVM  
Head, Animal Production Unit
FAO/IAEA Central Laboratory for ELISA and Molecular Techniques
FAO/IAEA Agriculture and Biotechnology Laboratory
P.O. Box 100
A-1400 Vienna Austria

Experimental infection of cattle with the agents of transmissible mink encephalopathy and scrapie.

Robinson MM, Hadlow WJ, Knowles DP, Huff TP, Lacy PA, Marsh RF, Gorham JR
J Comp Pathol 1995 Oct;113(3):241-51 
USDA-ARS Animal Disease Research Unit, Washington State University, Pullman , USA. 
Cattle are susceptible to experimental infection with the Stetsonville isolate of the transmissible mink encephalopathy (TME) agent. To determine if they are susceptible to other TME isolates, two groups of calves were inoculated intracerebrally with homogenate of mink brain containing the Hayward isolate or the Blackfoot isolate. For comparison, a third group was inoculated with a brain homogenate from a steer infected with the Stetsonville isolate in its primary cattle passage and a fourth group was inoculated with a pool of brain homogenate from three cattle experimentally infected with a sheep and goat scrapie agent in its primary cattle passage.

Clinical signs of neurological disease appeared in each steer of every group between 15 and 25 months after inoculation. An encephalopathy characterized by severe spongiform change and pronounced astrocytosis occurred in the three groups inoculated with the TME agent. In contrast, the neurohistological changes in the steers inoculated with the cattle-passaged scrapie agent were slight and subtle. Analysis of the octapeptide repeat region of the bovine protease-resistant protein (PrP) gene showed that variations in incubation period, clinical signs, and neurohistological changes were unrelated to the homozygous or heterozygous condition of six or six/five octapeptide repeats.

Experimental infection of mink with bovine spongiform encephalopathy.

Robinson MM, Hadlow WJ, Huff TP, Wells GA, Dawson M, Marsh RF, Gorham JR
J Gen Virol 1994 Sep;75 ( Pt 9):2151-5 
USDA-ARS Animal Disease Research Unit, Pullman, Washington 99164-7030. 
To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME).

Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.

Intracerebral transmission of scrapie to cattle.

J Infect Dis 1994 Apr;169(4):814-20 
Cutlip RC, Miller JM, Race RE, Jenny AL, Katz JB, Lehmkuhl HD, DeBey BM, Robinson MM
USDA, Agriculture Research Service, National Animal Disease Center, Ames, IA 50010. 
To determine if sheep scrapie agent(s) in the United States would induce a disease in cattle resembling bovine spongiform encephalopathy, 18 newborn calves were inoculated intracerebrally with a pooled suspension of brain from 9 sheep with scrapie. Half of the calves were euthanatized 1 year after inoculation. All calves kept longer than 1 year became severely lethargic and demonstrated clinical signs of motor neuron dysfunction that were manifest as progressive stiffness, posterior paresis, general weakness, and permanent recumbency. The incubation period was 14-18 months, and the clinical course was 1-5 months.

The brain from each calf was examined for lesions and for protease-resistant prion protein. Lesions were subtle, but a disease-specific isoform of the prion protein was present in the brain of all calves. Neither signs nor lesions were characteristic of those for bovine spongiform encephalopathy.

CWD trophies-- a worry for taxidermists?

18 May 99 Listserve discussion
Question: Are trophy deer and elk heads an ongoing hazard in people's dens? Could not dermal shedding of agent present a risk?

Answers: "Taxidermists actually take the hide off and tan it. Take off the horns, usually with part of the skull to keep it all intact and do some clean-up on the bone. Then re-apply all to and over a styrofoam model. There is no other bone or brain or soft tissue used."

"When trophy deer, elk, moose, etc heads are mounted the actual skull of the animal is not used. Either the hunter or the taxidermist skins the head and the skin is mounted on a fibreglass mold that is made and purchased specifically for this. The molds come in a variety of sizes. In states or provinces with a surveillance system on place for CWD these very same skulls/skinned heads would likley be submitted for the surveillance program."

Comment (webmaster): While appreciative for information about what is actually done in the process of creating a trophy from a CWD infected head, it sounds like most of the risk is taken on by the taxidermist, though the nose, eye area, and skin might still present risks despite tanning.

The chemistry of the tanning process might or might not affect dermal shedding of agent. Raw brain lipid itself is used as the tanning agent in survival/Indian arts courses taught in eastern Oregon today. I recall horrific problems from chromate and sulphuric acid used in the Chicago leather industry. Can anyone furnish a description of the chemistry likely to be used today by a small taxidermist?

Like morticians, one might assume that sensible precautions are taken within the profession. However, it turned out that American morticians are just this year becoming aware of possible risks from preparing CJD victims for burial. Perhaps someone from CJD Voice could contact Taxidermy Today to build awareness.

The CJD Foundation Message Board carries this message:

In my profession of funeral service, CJD seems to often be overlooked as a potentional hazard. with things like aids and hepatitis, the focus is quite clear. but CJD is more of a hazard than them combined. CJD has no know disinfecting agents available to us. Plus, with no abrupt symptoms of the disease, an embalming taken place years ago may have contaminated instruments used and still be contaminating everything it comes in contact with. This problem must be communicated to has many in my proffession as possible. Many people overlook funeral directors as potential contracters, but have to be amongst the highest of threats. Feedback please. Tom Rossi

Guidelines for CWD in Captive Elk

A Model Program for Surveillance, Control, and Eradication of Chronic Wasting Disease (CWD) in Domestic Elk was developed at the October 1998 meeting of the United States Animal Health Association (USAHA). This Model, which was developed through the initiative of the North American Elk Breeders Association, will be published in the USAHA Proceedings as a joint recommendation of the Committee on Wildlife Diseases and the Committee on Captive Wildlife and Alternative Livestock.

This Model sets minimum standards for herd surveillance and monitoring by calling for voluntary CWD testing of all elk 16 months or older that die in a herd. An annual herd inventory with verification by a state or federal animal health officer would be made, and elk herds would obtain a graded status depending upon the number of years monitored without evidence of CWD. Animals could be transferred among herds of equal or lesser status.

In the event of a diagnosis of CWD in a captive elk herd, the Model outlines mandatory steps for herd disposition. The length of the quarantine period depends upon whether the state veterinarian believes there is evidence of spread of CWD within the herd as opposed to a single case. The minimum quarantine for high risk animals (those that were in contact with a CWD-positive elk) is 4 years. Herd surveillance, which includes mandatory death reporting and CWD testing on all dead animals, must be done for 5 years after the last CWD case is diagnosed. There are provisions for sacrificing and testing the high-risk animals in the herd. High risk animals are elk that were pen-mates of an affected elk for any time up to 1 year prior to the death of the affected animal. Trace-back and trace-forward elk herds must be monitored for 3 years from the date of exposure to the affected animal.

The Model has been distributed to all state veterinarians. Although the surveillance aspect in the Model is intended to be voluntary among elk farmers, it is likely that many state veterinarians will make it mandatory.

A program to deal with CWD is greatly hindered by the lack of a proven test for live animals. Given this circumstance, the Model is a compromise that gives elk farmers a chance to prove that their herds are clean by long-term vigilance. Hopefully, a much-needed diagnostic test will surface soon so that the extent of the problem can be more clearly defined. Persons interested in a copy of the Model can contact SCWDS; the Model is published in the USAHA Proceedings as a 1998 recommendation of the Alternate Livestock Committee.. (Prepared by Victor Nettles)

Arkansas Elk Hunt

Elk were once found in much of the Southeast, and there has been considerable interest in restoration of elk to their historic range. The Arkansas Game and Fish Commission, in cooperation with private citizens, began an elk restoration project in the Ozark Mountains of northwest Arkansas in 1981. From 1981 to 1985, 112 Rocky Mountain elk from Colorado and Nebraska were introduced at sites near the Buffalo National River. Since that time, the Arkansas Game and Fish Commission and the National Park Service have conducted extensive habitat improvement projects, and the population has grown to about 450 animals.

In the fall of 1998, Arkansas held its first modern-day elk hunt as part of its elk management program. SCWDS has prepared a Model Health Protocol for Importation of Wild Elk for Restoration (see SCWDS BRIEFS Vol. 13, No. 3 and Vol. 14, No. 2). The Arkansas elk hunt was an excellent opportunity to evaluate the health status of a recently established population consisting of translocated elk.

SCWDS staff members examined and obtained samples from 17 elk. All elk examined appeared to be in good to excellent condition, and tests for diseases of major concern, i.e., chronic wasting disease, bovine tuberculosis, brucellosis, Johne's disease, and Pasteurella pneumonia, were negative. {Unfortunately, these animals were tested by histology alone, pers. comm Dr. Nettles 25 May 99] Serologic evidence of exposure to bluetongue, epizootic hemorrhagic disease, and leptospirosis was detected in some animals, but clinical signs or lesions resulting from these diseases were not evident. Parasitism due to lungworms, Sarcocystis, and ectoparasites was subclinical, and there was no evidence of blood parasites such as Anaplasma. However, there was histologic evidence suggestive of previous exposure to the deer meningeal worm, Parelaphostrongylus tenuis, which suggests that many elk can overcome infection with this parasite....

Immunohistochemistry: a superior diagnostic method

Listserve. Dr.Janice Miller 28 Apr 99
"Veterinary Record returned the manuscript in December with reviewer comments wanting a more detailed description of the neuroanatomical PrPSc localizations. Unfortunately, we were not able to meet such a requirement because the brain samples that had been collected were not appropriate. We withdraw the paper and the senior author is now rewriting the paper for submission to a different journal."

"With regard to specific information presented in the paper, it should be noted that the 17 animals examined were a selected group taken from a very large herd and the selection process was not intended to provide a valid assessment of overall CWD prevalence."

"The ability to detect positive brains in elk that had not yet developed clinical signs or lesions was reported several years ago using laboratory animal models of scrapie. In our 1993 and 1994 papers on the use of IHC for scrapie diagnosis in sheep, we reported finding many IHC positive brains that had been designated as only suggestive or inconclusive for scrapie by histopathological criteria. Since that time the APHIS National Veterinary Services Laboratory has been using IHC for diagnosis of TSEs."

"According to Drs. Linda Detwiler and Al Jenny, all brains from sheep, goats, cattle, deer, and elk with neurological disease are examined histologically and by IHC. Brains from the *downer cow* surveillance program are also examined by both tests. APHIS, with the assistance of state animal health and wildlife officials, has tested over 2,000 brain samples from free-ranging cervids in Nebraska, South Dakota, Kansas, Michigan, and New Jersey. All brains were negative for PrPSc by IHC."

"State diagnostic laboratories know about the availability of IHC testing at the NVSL and tissue samples from suspect cases are sent to that laboratory on a referral basis. IHC has been used routinely in the diagnostic laboratories of Colorado and Wyoming for several years so undoubtedly the 1998 prevalence report was based on that type of testing procedure."

Clarifications on immunohistochemical detection of preclinical CWD in captive elk

Listserve. Dr.Janice Miller 13 May 99
The number of positive animals found (10 of 17) should not be extrapolated to represent the whole herd because it was a selected group. The full text of the article states:

"Seventeen elk from a large captive herd in South Dakota were slaughtered in April, 1998. Individual members of the original herd were diagnosed with CWD in December, 1997. The owners reduced the herd in hopes of salvaging some of the animals for meat. Slaughtered elk were chosen based on young age and the likelihood that they were not yet infected. The slaughtered elk were all male, ranging in age from two to five years (9=2 years, 7=3 years, 1=5 years)."

"The five year old and one of the three year old elk exhibited clinical signs consistent with CWD as seen by the herdsman of the ranch. Three of the 17 elk, including the two elk with clinical signs, had histologic lesions consistent with CWD, including spongiform change of the gray matter neuropil, vacuolated neurons, and mild gliosis."

"Separately, a three year old aclinical animal displayed histologic lesions suggestive of CWD, including mild spongiform change in the gray matter of the medulla oblongata and cerebrum, a few vacuolated neurons, and mild gliosis in the brain stem and spinal cord. Medulla oblongata at the obex from each of the 17 elk were immunohistochemically examined for PrP-Sc according to the method of Miller and others, 1994. Tissues from 10 of the 17 elk (58.8 %) were positive."

This work strongly validates concerns about horizontal transmission in elk. I have heard Drs. Mike Miller and Elizabeth Williams speak many times and they always stress that the epidemiology of CWD indicates it is laterally transmitted. Dr. Williams spoke just last week here in Ames and her handout about CWD states:

"The mode of transmission of CWD is not known. Epidemiologic evidence strongly suggests lateral transmission occurs among deer and elk and probably from mule deer to elk and white-tailed deer. Maternal transmission may occur but does not explain many cases of CWD. Concentration of animals in captivity may facilitate transmission; however, CWD is maintained in populations of deer even at moderate to low populations densities."

Dr. Mike Miller's most recent publication (Epidemiology of Chronic Wasting Disease in Captive Rocky Mountain Elk, Journal of Wildlife Diseases 34:532-538, 1998), states the following:

"Our observations provide compelling circumstantial evidence for lateral transmission of CWD among elk. We believe the most plausible explanation for the epidemic pattern observed in this captive elk herd is animal-to-animal transmission of CWD."

Preclinical detection of scrapie and BSE: Papers describing detection of PrP-res in tissues without histopathologically detectable lesions: in addition to our 1993 and 1994 papers that describe this situation in sheep scrapie, there are other similar reports in the literature. One of the most thorough studies was by Bruce, et al., published in 1994 (PrP in Pathology and Pathogenesis in Scrapie-Infected Mice, Molecular Neurobiology 8:105-112). The following statement summarized the work on serial examinations of PrP accumulation:

"PrP changes were first seen relatively early, between a fifth and a quarter of the way through the intracerebral incubation period, depending on the model, and many weeks before the development of vacuolar degeneration. Abnormal distributions of PrP appeared at about the time that relatively protease-resistant PrP became detectable by Western blotting."

An earlier report by Lantos et al. also described the greater sensitivity afforded by immunohistochemistry in human prion diseases (Prion protein immunocytochemistry helps to establish the true incidence of prion diseases, Neuroscience Letters 147:67-71, 1992). The summary states:

"It has been reported that prion diseases may occur without the histological hallmarks of spongiform encephalopathies: vacuolation of the cerebral grey matter, neuronal loss and astrocytosis. These cases without characteristic neuropathology may go undiagnosed and consequently the true incidence of transmissible dementias is likely to have been under-estimated. Immunocytochemistry using antibodies to prion protein gives positive staining of these cases, albeit the pattern of immunostaining differs from that seen in typical forms. Accumulation of prion protein is a molecular hallmark of prion diseases, and thus a reproducible, speedy and cost-efficient immunocytochemical screening of unusual dementias may help to establish the true incidence of prion diseases."

A paper published last year by Wells et al. (Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update, Veterinary Record 142:103-106, 1998) describes an experiment done in the UK in which cattle were experimentally exposed orally to BSE and necropsies were conducted at periodic intervals for examination of tissues by histopathology, immunohistochemistry, and mouse bioassay. After a discussion of similar studies done earlier in sheep scrapie, the paper reports the following relative to immunohistochemistry results: "

Table 2 also shows the IHC and BSE fibril results from 32 months after inoculation, the time after which abnormal PrP was detected in the CNS. This change preceded the pathognomonic histopathological changes in the brain, and the onset of clinical signs, and was most consistently detected in the lumbar spinal cord." (Note: 3 cattle killed 36 months after exposure were positive by immunohistochemistry but only 1 had histopathologic lesions of BSE.)

On the use of immunohistochemistry by APHIS for its BSE surveillance: All *downer cow* brains collected in the collaborative study conducted by APHIS and FSIS (Food Safety and Inspection Service) are examined with this technique at the APHIS lab in Ames [note rabbit polyclonal antibody must have been used early on -- a weaker reagent] . Bovine brains from rabies suspects are submitted to state public health or animal health diagnostic laboratories and tissues from non-rabid animals are sent to Ames for the BSE examinations.

All veterinary pathologists should now be well aware of CWD and the need for immunohistochemistry testing. In fact, that is how the cases in captive elk in South Dakota, Nebraska, and Oklahoma were found. The last annual meeting of the American Association of Veterinary Laboratory Diagnosticians (October, 1998) featured 3 talks on CWD. Dr. Beth Williams gave an overview of the disease, Dr. D.H. Zeman described the identification of CWD in South Dakota commercial elk facilities, and Dr. Al Jenny presented results from the APHIS survey for CWD in deer (that information although it has not yet been submitted to a journal).

Dr. Jenny will be presenting results of the current year's survey at the next AAVLD meeting (October, 1999). These meetings are attended by representatives from every animal health diagnostic laboratory in the country, so I think it is very likely that any current and future suspect CWD cases will be referred to APHIS for immunohistochemical testing.

With regard to the question about whether immunohistochemistry was used in CWD surveys done in endemic areas (Colorado and Wyoming) prior to 1998, the technique has been used since 1995 (see remarks of Dr. Mike Miller in the attached USAHA report). In January of this year all of the people involved in CWD research attended a meeting in Fort Collins and Dr. Mike Miller reported on their survey results to that point in time. Everything I heard him say indicated that both the targeted and hunter-kill surveillance efforts are continuing annually in both deer and elk. The histopathology and immunohistochemistry work for these surveys is not done by Colorado Fish and Game but by Dr. Terry Spraker at the Colorado State Veterinary Diagnostic Laboratory.

It is true that my comments about results of the APHIS survey on wild cervids involved only deer. That is not surprising because the states where those studies were conducted do not have many (or any) elk. Dr. Jenny told me that there were a few elk brains in this year's collections from South Dakota and Nebraska and they were all negative. That data has not been tabulated and is not included in the information I cited earlier.

Could the immunohistochemical test to brain tissue be applied to the 12-year old cow that was in contact with CWD deer and elk at the Foothills Research Station? That would certainly be possible if paraffin blocks of the animal's brain are available. However, unless the animal showed clinical signs of a CNS problem (which apparently it didn*t) it is unlikely that brain tissue would have been collected for histopathologic examination. If such material exists, however, it could certainly be examined by Dr. Spraker at the Colorado Veterinary Diagnostic Laboratory since he is very experienced with both the histopathology of CWD and the immunohistochemistry procedure for detection of PrP.

Should tonsil tissue from hunters in the Fort Collins area be subjected to PrP immunohistochemical examination? Personally, I hope that clinically healthy people are not encouraged to subject themselves to a surgical procedure of that nature, because there is always a certain degree of risk involved. However, even if hunters are willing to participate in such a study, or if archived tonsillectomy samples are available, I feel it would be totally inappropriate for me to do an immunohistochemical test on a tissue and species with which I have no experience. Although I have many years of experience in applying the test to brains of ruminants, only in recent months have I begun to investigate its use on lymphoid tissues of sheep (which I find presents a much more difficult challenge with respect to interpretion of staining reactions).

Furthermore, we don't even know if our reagents would work on human tissue (many PrP antibodies are species specific). A laboratory that has used immunohistochemistry to detect PrP in lymphoid tissues from CJD and nvCJD patients would be more suitable.

TSE discussion highlights sheep and goal disease committee meeting

Oct. 5, 1998 United States Animal Health Association press release
MINNEAPOLIS, Minn-- There is an ever-increasing focus on transmissible spongiform encephalopathies (TSEs) throughout the world -- expecially in reference to sheep and goats.

Dr. Linda Detwiler with the U.S. Department of Agriculture's Animal and Plant Health Inspection Service told the USAHA committee on sheep and goats, which met here today, that one of the biggest concerns of the international sheep and goat industry is the possibility that bovine spongiform encephalopathy (BSE) exists in the native sheep and goat populations of the United Kingdom and other European countries because of exposure to BSE-contaminated meat and bone meal. BSE has been expermentally transmitted via feed to sheep, but no natural disease has been identified to date. Surveillance studies are underway in the UK to look for BSE in the sheep and goat populations there.

Dr. Detwiler said that because of this possibility, importation of sheep and goats into the United States has been prohibited except from Canada, Mexico, Australia and New Zealand.

She also said that the Organization International des Epizooties (OIE) is establishing international guidelines and standards for declaring a country free of sheep scrapie and for trade in live animals, germplasm and products with respect to this disease.

Dr. Diane Sutton, also with USDA-APHIS, provided the committee with an update on the scrapie program. APHIS currently addresses scrapie through two approaches: (1) a regulatory program to prevent the interstate movement of infected and high-risk animals and (2) the Voluntary Scrapie Flock Certification Program, which is designed to identify scrapie-free and reduced-risk animals. APHIS is currently drafting a proposed rule in response to a 1996 USAHA resolution and a Jan. 26, 1998, advanced notice of proposed rulemaking regarding the interstate movement of sheep and goats from states that do not quarantine scrapie-infected and source flocks.

APHIS is also developing a new generic data base, which is year 2000 compliant, to improve the accuracy and timeliness of information provided on the APHIS flock status web pages (www.aphis.usda.gov/vs/scrapie/).

Dr. Katherine O'Rourke with USDA's Agricultural Research Service told the committee that a live animal test for scrapie, described last spring, has been revised twice to improve sensitivity and specificity. She anticipates a two-year validation test involving U.S. sheep.

Dr. Nora Wineland with USDA-APHIS reported on a possible National Animal Health Monitoring Service national study for sheep in the year 2000. This means that a needs assessment to find the largest "information gaps" must be completed by the spring of 1999.

CWD in Arkansas? -- no IHC testing

SCWDS Briefs newsletter. Arkansas Game & Fish Commission Little Rock, AR 72205 tel 501-223-6300
JASPER - Saturday, Aug. 1,1998 is when the 18 remaining elk hunting permits for 1998 will be drawn. More than 16,000 persons applied for the free elk-hunting permits.

Return of the Elk

by Michael E. Cartwright, Deer/Elk Program Coordinator, Arkansas Game and Fish Commission
Elk once numbered in the millions and occupied habitats spanning most of North America. Unfortunately, shrinking habitat and overhunting reduced populations to a few persistent herds in the mountainous West. Had the elk not been remarkably adaptable, it might now be extinct.

The eastern elk (Cerrus elaphus canadensis) lived in eastern boreal and hardwood forests. This was the subspecies native to Arkansas, though historical records indicate it persisted no later than the 1840s. It is now extinct. The U.S. Forest Service introduced Rocky Mountain elk (Cersus elaphus nelsoni) in Franklin County's Black Mountain Refuge in 1933. Three bulls and eight cows from Wichita National Wildlife Refuge in Oklahoma were released. The population grew to 125 by 1948, but by then, wildlife biologists were concerned about the herd's future.

The herd increased to an estimated 200 by the mid 1950s and then vanished. No one knows for sure what caused these elk to disappear. Some speculate that illegal hunting, natural mortality and shrinkage of suitable range through natural ecological succession eventually resulted in their extermination.

In 1981, the Game & Fish Commission, in cooperation with private citizens and the National Park Service, initiated another elk restoration project in the Ozark Mountains of northwest Arkansas. Between 1981 and 1985, 112 elk from Colorado and Nebraska were released at five sites near Pruitt in Newton County.

All release sites were on or adjacent Buffalo National River lands. Some elk were ear-tagged and tested for diseases such as brucellosis and leptospirosis prior to release. The Game & Fish Commission and Park Service monitor elk using field observations, helicopter counts and, in recent years, thermal infrared sensing equipment. Elk have been reported in Washington, Carroll, Boone, Marion, Newton, Searcy, Stone, Conway, Pope, Van Buren and Faulkner counties, but most of the approximately 350 elk in the Arkansas herd occur along 67 miles of the upper and middle Buffalo National River corridor in Newton and Searcy counties, primarily on National Park Service land.

Fifty-five elk deaths were documented between 1981 and 1993. Poaching (32 percent) and disease (31 percent) are primary factors in these losses. Without suitable habitat, elk would soon disappear from Arkansas. Realizing this, state, federal and private interests have worked together to expand and improve elk habitat along the Buffalo River. Arkansas's First Elk Season Set By Game and Fish Commission

Arkansas Elk Hunt

"Elk were once found in much of the Southeast, and there has been considerable interest in restoration of elk to their historic range. The Arkansas Game and Fish Commission, in cooperation with private citizens, began an elk restoration project in the Ozark Mountains of northwest Arkansas in 1981. From 1981 to 1985, 112 Rocky Mountain elk from Colorado and Nebraska were introduced at sites near the Buffalo National River. Since that time, the Arkansas Game and Fish Commission and the National Park Service have conducted extensive habitat improvement projects, and the population has grown to about 450 animals." "In the fall of 1998, Arkansas held its first modern-day elk hunt as part of its elk management program. SCWDS has prepared a Model Health Protocol for Importation of Wild Elk for Restoration (see SCWDS BRIEFS Vol. 13, No. 3 and Vol. 14, No. 2). The Arkansas elk hunt was an excellent opportunity to evaluate the health status of a recently established population consisting of translocated elk. "

"SCWDS staff members examined and obtained samples from 17 elk. All elk examined appeared to be in good to excellent condition, and tests for diseases of major concern, i.e., chronic wasting disease, bovine tuberculosis, brucellosis, Johne's disease, and Pasteurella pneumonia, were negative. [Unfortunately, these animals were tested by histology alone, no immunohistochemistry, pers. comm Dr. Nettles 25 May 99 to webmaster]

Serologic evidence of exposure to bluetongue, epizootic hemorrhagic disease, and leptospirosis was detected in some animals, but clinical signs or lesions resulting from these diseases were not evident. Parasitism due to lungworms, Sarcocystis, and ectoparasites was subclinical, and there was no evidence of blood parasites such as Anaplasma. However, there was histologic evidence suggestive of previous exposure to the deer meningeal worm, Parelaphostrongylus tenuis, which suggests that many elk can overcome infection with this parasite.... "

Arkansas elk re-introduction: animals from high-risk states used

Comment (webmaster): These elk came from high risk states at a time when CWD was first getting established in wild elk and research facilities. The state fish and game site does not disclose whether these were wild or captive elk, nor what subsequently transpired at those facilites.. The investigative pattern, as in many states, is to bow to hunters' concerns and take a look for CWD, but use the worst methods possible. In the last 6 months, Oregon and Arkansas have both opted to used methodologies from the 1970's. Yet prion monoclonals have been around for 13 years:
Barry RA, Prusiner SB l. Monoclonal antibodies to the cellular and scrapie prion proteins. 
J Infect Dis. 1986 Sep;154(3):518-21

Prusiner SB  et al. Acta Neuropathol (Berl) 1987;72(4):299-314  
"Monoclonal antibodies to PrP 27-30, as well as antisera to PrP synthetic peptides, specifically react
with both PrPC and PrPSc, establishing their relatedness."

Kascsak RJ, et al.  
Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. 
J Virol. 1987 Dec;61(12):3688-93. 
Affinity BioReagents in Colorado now offers:

PA1-750, Polyclonal (Rabbit) Anti-Cellular Prion Protein.

PA1-750 was produced by immunizing New Zealand White rabbits with a synthetic peptide (Cat. # PEP-034) corresponding to amino acid residues 90-102 of human PrP. Peptide sequence: G90 Q G G G T H N Q W N K P102 G G C. This product is for in vitro experimental use only, and is not intended for use in humans or clinical diagnosis.

MA1-750, Monoclonal (Mouse) Anti-Prion Protein

Monoclonal antibody F89/160.1.5 directed at ruminant prion has been licensed from USDA and is currently in the ascites production phase. They expect to have this material in IgG purification/testing by the middle of June 1999. If an evaluation at Pullman is satisfactory, it will be available at that time. At this time they are taking people's numbers so they can let them know about the antibody as soon as it's ready. {Contact: Phillip E. Schwartz, Director of Scientific Development, Affinity BioReagents, Inc.

The 1999 USAHA/AAVLD Annual Meeting meeting

Preregistration (Non-Members) $200.00
Thursday - October 7, 1999.   AAVLD BSE Workshop - 9:00am-12:00noon, California Room.
Sunday - October 10, 1999  AAVLD-USDA Emergency Disease Liaison Committee - 4:00-5:00pm; Esquire Room.
Monday - October 11, 1999 . Foreign Animal Diseases Committee - 12:30-5:30pm; San Diego Room.*
...National Cattlemen's Beef Association - 8:30am-12:00noon; De Anza Room.
...National Scrapie Oversight Committee Meeting - 9:00am-12:noon; Cabinet Room.
Tuesday, October 12, 1999. Captive Wildlife and Alternative Livestock Committee - 7:00am-12:00noon;  Chamber Room.
Wednesday, October 13, 1999.  Wildlife Diseases Committee - 7:00am-12:00noon; Senate/Committee Room.

*The 1998 Grey Book of Foreign Animal Diseases can be ordered for $25.

The USDA's secret scrapie non-survey

24 May 99 transcript of USDA FOIA documents
Commentary (webmaster):

Recently, K. O'Rourke's new ruminant monoclonal enabled for the first time a good survey of preclinical scrapie in the US. She sensibly concluded one paper on successful preclinical detection of scrapie with:

"Until we have a better understanding of intraspecies and interspecies transmission of TSEs, it would be prudent to remove all prion postive sheep from breeking flocks and from the food chain."

J. Miller determined the costs of a 3,000 sheep slaughterhouse survey to be a pittance, $27,500 in an agency with an 11 digit budget. That's $9 per sheep.

But there was one itty-bitty problem for USDA. ARS didn't want to expend all this effort only to have it buried without at least an internal document being produced. And so the survey never got done. Or it got done without a paper trail being created. Or a paper trail was created but they held it back from the FOIA requestors. Perhaps too many of the sheep would be found infected.

The US had about 8.5 million sheep. The ones with preclinical scrapie presumbably entered the human food chain.

Now which sheep parts are infected? Thirty months earlier, on 8 July 1994 John Gorham [USDA, ARS, Pullman] had written to Tom Walton discusson the occasion of the 30 June 1994 MAFF announcement of BSE infectivity of calf ileum:

"Here is where the real cruncher comes. Sheep offal from lambs less than one year of age is currently legally rendered in most US plants. If it is found that scrapie infectivity is in the intestine of lambs and all rendering of sheep is prohibitied, it will be a severe economic hardship on those producers raising lambs. It is not economically favorable to raise lambs for the meat alone. They need a market for the offal (dog food, fertilizer, bone meal, etc.) and an economical way of disposing of the carcasses. Katherine [O'Rourke] is currently investigating the infectivity of tissues from preclinical sheep. We'll have a chance to discuss this is September [1994]."

But there was another itty-bitty problem for USDA. ARS didn't want to expend all this effort only to have it buried without at least an internal document being produced. And so the tissue survey never got done. Or it got done without a paper trail being created. Or a paper trail was created but they held it back from the FOIA requestors. Perhaps too much of the sheep would be found infected.

And here we are in May, 1999. The US still has millions upon millions of sheep. We still have not the slightest idea what fraction of US sheep have scrapie nor which tissues consumed by humans are affected. The ones with preclinical scrapie presumbably still enter the human food chain.

How many scrapie sheep were eaten by people in the years since the scrapie survey became feasible? Why not test _all_ the sheep at slaughter if it is just it is only a dollar or two per sheep?

Then there is the matter of the never-published strain-typing of US scrapie [below]. This had potential for undermining confidence in sheep-to-cow passage studies of scrapie in US cows not resembling UK BSE. All in all, USDA is shirking its duty . Whered is the accountability here to the taxpayers providing that 11 digit annual budget?

18 Dec 96 memo from Janice Miller to Linda Detwiler:

"After our discussion last week concerning the possibilities for an APHIS/ARS collaboration to do a scrapie survey using immunohistochemistry, I talked with Randall Cutlip regarding the extent to which NADC could become involved. We investiggated the direct costs associated with such a venture and decided that enough resources will be available during FY97 to examine 3,000 specimens (1 slide per animal). This commitment requires a financial outlay of $27,500:
-- $7.50 per specimen to embed and prepare 1 unstained section: $22,500
-- labor for IHC (10 weeks): 3,000
-- staining reagents: $2,000.
"...We plan to hire a college student to do the staining procedure during the summer vacation months.... Our histopathology laboratory can handle about 200 extra specimens per week (in addition to their routine activities)..."

"...the monoclonal antibody reagent developed by O'Rourke is a better quality reagent than the arabbit antibody we currently use, in terms of both staining quality (low background) and its anti-PrP titre. "

"I'm sure you understand that an ARS commitment to a project of this size carries with it the expecgation that some kind of documentation (preferable a paper in a refereed journal) will be forthcoming. That's one thing that certainly will need discussion..."

"My understanding of the resolution passed by the Sheep and Goat Committtee at the recent USAHA meeting it taht it requests a survery to establish the prevalence rate of scrapie in the US. Al [Jenny] pointed out to me that since some adult sheep are sent to Mexico for slaughter, we may not be able to acquire the type of samples needed to address the [sampling protocol] issue. If so, do we still want to attempt the work anyway? Would it be useful to do a survey that would just dertermine the incidence of scrapie in sheep that are slaughtered in the US?

Comment (Dr. Janice M. Miller on 24 May 1999 ): "I see some clarification is again needed regarding an ARS activity, i.e. our involvement in the planning for a U.S. sheep scrapie survey. The original offer we made to APHIS for a test of 3,000 brains was never carried out because we determined that a prevalence estimate (obtained through producer surveys) indicated the need for a much larger sample number (10 to 11 thousand) than we were prepared to undertake with our resources."

"Furthermore, to have any kind of statistically valid data it will be necessary to collect material from representative plants at particular times of the year (because of the seasonality of lambing) and that requires extensive long-range planning and preparation. At this point in time APHIS is still planning to do a survey, although the exact timing has not been determined. A training session for field people was held here in Ames just last month to assure that samples would be taken and submitted correctly. Contacts are currently being made to secure the cooperation of FSIS and appropriate slaughter plant owners (remember that the federal government has no authority to demand their participation). "

"It is expected that the survey would be completed within a year from the time it is begun (at least the collection phase). That will create a very heavy drain on the resources available to APHIS field personnel and they can not take that on without considerable time to plan for accomodating the requirements of that effort. Remember that they have many responsibilities to ongoing programs for other diseases (tuberculosis, brucellosis, etc.) as well as the unexpected emergencies that invariably arise (e.g. avian influenza outbreaks)."

"The collection of thousands of sheep brains at specific times in specific locations and getting them processed at the NVSL laboratory is a huge project. Besides the time needed to plan for implementation of the survey itself, there is another important consideration that impacts when the survey would begin. A rule has been proposed to require some kind of identification on sheep that are going to slaughter that would indicate the state of origin. Having such a rule in place before doing the survey would be a tremendous bonus because APHIS could get good information about regional scrapie prevalences. Knowing where the sheep are slaughtered doesn't do any good because they can, and frequently do, cross the country (in both directions) when going from the farm to a slaughter plant and some may go through several different buyers in the meantime so it isn't feasible to try to trace their movements."
"As I said, a rule has been proposed to require a tag that will show state of origin but I don't know what the status of that is. To my knowledge it has not yet appeared in the Federal Register and I believe that after that occurs a certain comment period is required before anything else can happen. Another problem to be solved before going ahead with the survey is to decide what can be done about the sheep going to Mexico. The numbers that go there can fluctuate wildly, depending on market conditions in the 2 countries. APHIS is doing a lot of investigation to see if there is some way to accurately access what that missing information will do to the validity of the final data."

"Finally, I would like to make some points about the cost involved in the kind of work being planned. As my memo indicated, we felt it would cost us (ARS) at least $9 per sheep to get the tissues processed and to pay for the student labor and reagents to do the staining procedure. Furthermore, because I was going to do it as a research project, I didn't include any cost for a pathologist's time to cut in the tissues and examine the slides. I certainly don't see how APHIS could run the test for a lesser cost because they surely would have to hire some extra technical, and perhaps professional, staff. I think it would be impossible for them to conduct a project of that magnitude with just their current personnel, who already have a full-time commitment to other programs (e.g., right now they are being overwhelmed with tuberculosis samples because of recent unexpected problems involving that disease).

"I think it is also important to understand that there are other costs involved in the proposed survey besides just the laboratory testing. Kits for sample collection and shipment would not be cheap (materials and labor for assembly) and the costs for shipment of samples will be substantial. I think when all these things are considered the scrapie survey will be quite an expensive undertaking and since Congress has made no special appropriation for it, the costs will have to be absorbed through the regular APHIS budget, which I'm sure is not an insignificant problem for them."

K. O'Rourke et al: manuscripts, submitted, in progress, or in preparation.

[These are not scandalous in any way, simply scientific papers at various stages of preparation that USDA determined were public documents.]

1. Codon 129 is polymorphic in elk. [Presumbably leucine seen in 3 German zoo elk is also a moderately common allele in wild elk].

2. Validation of nictitating membrane-associated lymphoid tissue IHC assay as a diagnostic test for CWD in cervids.

3. Analysis of prion genes from Rocky Mtn elk, mule deer and white-tailed deer with CWD.

4. Characterization of the cell types and receptors associated with PrP-scrapie in the peripheral lymphoid tissue and peripheral blood.

5. Preclinical detection of PrP-scrapie in nictitating membrane-associated lymphoid tissue of sheep.

"Although susceptibility to scrapie has been defined genetically, a large percentage of US suffolk sheep carrying ths susceptible genotypy 136AA, 171Q do not develop scrapie, even in heavily infected flocks. Thus, in the US, maternal exposure is a better parameter than PrP genotype when selecting high risk sheep." Seven positive sheep were found in 4 flocks; four were born to clinically affected ewes. One positive sheep (#5), still healthy at age 3, was born 2 years before her dam developed scrapie. Twin offspring of sheep 5 were both positive at age 1 year."

"Until we have a better understanding of intraspecies and interspecies transmission of TSEs, it would be prudent to remove all prion postive sheep from breeking flocks and from the food chain." [The US has about 8.5 million sheep.]

Recall that these researchers earlier tested 88 sheep from 11 flocks with a history of scrapie. 25 healthy seeming sheep tested positive and 15 have gone on to develop signs of disease so far. [12 May 1998 USDA memo to Wool Growers citing a draft press release from WSU.]

On July 1995, 110 flocks were in the Voluntary Scrapie Program, 65 that are infected, and 6 source flocks [two positives under 54 months in last 5 years]. The scrapie indemnity program ended 8 July 1993.

6. Are sheep with the low susceptibility genotype silent carriers of scrapie infectivity? 5 year experiment initiated in 1996.

7. [Appeared but not indexed by Medline until vol 9]: Allelic frequencies of an ovine scrapie susceptibility gene. Animal Biotechnology 7. 155-162 1996.

8. Monoclonal F89/160.1.5 recognizes a conserved epitope on Prp-Sc in formalin fixed, paraffin-embedded brain tissue of sheep, cattle, goats, mule deer, and elk after hydrated autoclaving. J Clin Microbiol. 1998 Jun;36(6):1750-5. "...cocktails of MAbs to multiple variable epitopes would provide specific, reliable, and flecible toos for the accurate diagnosis of TSE in mammals."

Positive prion immunostaining detected in: -- healthy offspring of scrapie-affected ewes, -- healthy sheep in infected flocks

No staining detected in:
-- sheep from 4 flocks with no reports of scrapie.

8 July 1994 USDA memo from John Gorham [USDA, ARS, Pullman] to Tom Walton.

The 30 June 1994 MAFF announcement of BSE infectivity of calf ileum is discussed.
"Here is where the real cruncher comes. Sheep offal from lambs less than one year of age is currently legally rendered in most US plants. If it is found that scrapie infectivity is in the intestine of lambs and all rendering of sheep is prohibitied, it will be a severe economic hardship on those producers raising lambs."

"It is not economically favorable to raise lambs for the meat alone. They need a market for the offal (dog food, fertilizer, bone meal, etc.) and an economical way of disposing of the carcasses."

"Katherine [O'Rourke] is currently investigating the infectivity of tissues from preclinical sheep. We'll have a chance to discuss this is September."

The HyClone bibliograpby of smuggled fetal bovine serum articles is posted elsewhere.

Preliminary evidence of multiple strains of scrapie in the US.

Cutlip, RC,. Miller, JM, Jenny AL
Manuscript in review 1994-95.  Never published.
Isolates from 15 scrapie sheep (from 8 states -- Colorado, Iowa, Illinois, Kansas, Michigan, Virginia, Wisconsin, and South Carolina) were inoculated into C57/B6 inbred mice. 9 of the sheep brains gave rise to scrapie in the mice but without significant differences in extent or distribution of lesions or prion protein. Of 114 mice, 89 had both lesions and prion protein, 24 only prion protein, and 1 only lesions.

The length of incubation period varied greatly from 281-484 days with major breaks at 53, 63, and 79 days, supporting the idea of at least 4 scrapie strains in the US. However, some of the differences in length of incubation period could have been due to varying doses of agent. The genotypes of the donor sheep were not determined nor was there serial passage.

Multiple scrapie strains complicates testing of US scrapie in cattle. The experiments done so far do create US mad cows but not ones similar to UK mad cows. Just as with the origin of BSE in the UK, there is always the question of what would have happened if only some further strain had been tested.

The next lab to visit was Caughey-Cheesbro but this got left off the group's FOIA as it is under NIH not USDA.

Hunkering down in the APHIS BSE Situation Room

15 May 99 USDA FOIA response document, listserve discussion, webmaster opinion
A bizarre internal USDA publication dated October 1998 describes a James bond-type US effort to control media should the long-anticipated first case of BSE in the US be admitted. The document has become available as pdfat APHIS, making it invisible to Internet search engines.

Players on the 27 member BSE Response Team are to be flown in from all over the country to a BSE Headquarters 'situation room, ' apparently an underground bunker (Unilt 41) in Riverdale, Maryland under the command of the Assistant Secretary of Marketing and Regulation, one of many "line officers" on the Team.

Authentic-looking press releases are already prepared and ready to go out after a few specifics have been filled in such as the name of the cow. They are spelled out in a separate document, the BSE Red Book, aka BSE Emergency Disease Guidelines, which is not available online.

Aphis' National Veterinary Services Laboratories (NVSL) is given the mission of activating team assembly. From the time a bovine brain sample is submitted, it takes 14-18 days to confirm a diagnosis of BSE. In the first 10-13 days, NVSL have enough information to determine the need for additional tests. If a provisional BSE diagnosis is made, the sample is 'hand-carried' (are they going to tell the airline and customs?) to the Central Veterinary Laboratory in England for confirmation, where they are expecting a 24 to 96 hour turn-around.

Does this mean we can get the white tiger brain analyzed by Friday despite the 22 year delay to date. Maybe we could throw in a few cougar brains from NE Colorado too.

A Team Member is designated to silently monitor the Internet -- for what, it doesn't say. The Freedom of Information Act request from the East Coast consumer group turned up numerous "top-secret" USDA downloads from this site and Dr. Dealler's.

After 24 hours of secret briefings for 'select industry and trading partners' (to allow them to take positions on the commodities markets opposite the 'non-select' industry and trading partners?), a press conference will be held the following day.

There are plans to trace the cow, its lineage, its herdmates, the renderer, traceout of product, buyout of herd, farm of origin, to get the state involved to quarantine the herd (pre-arranged for all 50 states), expectations for trade bans, notification of OIE within 24 hours, media 800 numbers, spokespersons and backups, notify CDC, FDA, NIH, and many other commendable activities. In short, that cow is going to be toast by the time the public first hears about it.

The Flow Chart is a sight to behold:

The Plan does not speak to the scenario in which the CVL says, yes, this is bovine spongiform encephalopathy all right but it is one of your strains, not ours. There may be no perceived need for public disclosure in this case.

USDA is caught completely unprepared if BSE first turns up in a US zoo animal. These animals could easily be diagnosed outside the "system" and be the subject of a publicity-seeking lab press release. This is a more likely scenario because the US has likely imported many thousands of zoo animals with advanced infections from Britain and France and there has been no monitoring. Unlike with downer cows, anyone with the right friends can get brain samples from a fallen zoo animal. Zoo animals enter the food chain in some cases after being rendered.

Another scenario would be some stock market speculator obtaining the Red Book and issuing a flurry of bogus but authentic-looking press releases that included phony 800 and hacked USDA web links. The press here is so lazy and so accustomed to putting out public relation handouts as news that the objectives would be accomplished for a few hour (or days, depending on the Response Team's paralysis vis-a-vis off-flow chart events). Some people think a practice run for this happened in the Indiana case a year or two back.

The first case of nvCJD in an American will also be a public relations fiasco. In the dim bulb of the public mind, any American with mad cow disease would have gotten it from eating meat in the US.. USDA has no way to prove that the victim acquired it on a three week trip to England in 1987. This will sound lame even to the press. All CJD is synonymous with mad cow disease in the public perception; the more often the different kinds are explained, the more their suspicions are aroused. The first case of nvCJD in an American will simply validate what they already know and just be viewed as an overdue admission from the government.

USDA responds:

"The updated BSE Response Plan has been posted on the APHIS website for months. It was also distributed to the contact list which includes other government agencies, industry and consumer groups [but not to the BSE-L listserve which most people professionally involved with TSE read]. The USDA BSE website will keep this site up to date on an almost hourly basis, there is no intention of monitoring the sites of others. If anyone has questions about the document I can be reached as follows:

Linda A. Detwiler
Senior Staff Veterinarian
USDA, APHIS, Veterinary Services
609-259-5825"

Comment (webmaster): Yes, I have five questions please:

1. Could you please post the contact list of industry and consumer groups? My concern is that these are not bona fide consumer groups but simply industry-funded shells. It is important as a tax-supported public agency for USDA to promote a level playing field.

2. How do I go about getting my name added to this contact list to receive future secret messages? Could these not be posted more simply to the professional listserve?

3. Could you please post here a list of the "select industry and trading partners" that get the one-day advance warning that mad cow disease has been confirmed in the US? There are many stakeholders in this issue including public health and consumer interests -- I am hoping this list will demonstrate balance.

4. Please add my stockbroker to this list (my select trading parter). Billions of dollars will change hands -- I want to be among those getting the 24 hour advance notice. Could not the USDA provide an online sign-up opportunity for every trader?

5. Could you please post here copies of the press releases that have been made up in advance of this hypothetical event? The facts are not even in, how it is possible to issue reassurances to the consumer already? Maybe the actual event won't be all that reassuring.

EU's Fischler asks US to analyse science in beef row

Reuters World Report Wed, May 19, 1999
DUBLIN - European Farm Commissioner Franz Fischler said on Wednesday a transatlantic trade war over hormone-treated beef was in no-one's interest and urged the United States to examine the EU's new science on the issue. Referring to the EU's decade-old ban on imports of beef treated with growth hormones, which has plunged the bloc into another trade row with the United States, Fischler said delicate consumer confidence in the safety of beef was at stake.

"In the case of hormones we have believed for a long time that the use of these products in beef production does threaten human health," he said in a speech prepared for delivery to the World Meat Congress in Dublin. U.S. Agriculture Secretary Dan Glickman was also due to address the conference and the two have a breakfast meeting planned for Thursday.

But with entrenched positions on both sides, there still seems no easy solution. "Let me stress there is no ulterior motive to this measure but the protection of human health...and I would urge the authorities concerned to accept our invitation for discussion between scientists from different countries," Fischler said. "It is in no-one's interest to enter into confrontation on this issue."

The United States has applied to the World Trade Organisation for authorisation for $202 million in punitive duties on as yet unspecified EU goods in retaliation to the EU's ban, which it says hits its cattle industry hard and sets a damaging precedent in international trade. But Fischler said the U.S. cattle industry itself could be damaged by an escalation in the dispute, which has followed quickly on the heels of a transatlantic battle over bananas.

"I fail to see how beef producers using hormones in their production system can benefit from confrontation. It is quite clear they can only lose if consumer confidence is undermined." He called on the WTO, which following an intended challenge from the EU, is likely to rule on an appropriate level of U.S. sanctions, to work on solving the row in a non-punitive way.

"I hope that over the next weeks in discussions with our trading partners we can find a WTO-compatible solution which is mutually beneficial and trade expanding rather than trade contracting as the application of sanctions would lead to."

The EU is pushing to offer Washington compensation for its lost beef trade in the form of increased market access for other goods. However, the United States has so far refused to consider compensation without a firm commitment from the EU to lift the hormone ban at some future point.

EU-US Hormone Beef Dispute: No Deal But Talks To Continue

Thu, May 20, 1999 Dow Jones By Myles Neligan DUBLIN --U.S. Agriculture Secretary Dan Glickman and his European Union counterpart Franz Fischler ended a meeting Thursday without settling the E.U.-U.S. trade dispute over hormone-treated beef, but said the talks were "useful" and pledged to continue the search for a compromise. The two are due to meet again in Vancouver on July 16-18 at the annual meeting of the "Quint" group of trading nations, comprising the U.S., the E.U., Australia, Canada, and Japan.

Glickman said that in the meantime, "intensive" talks will take place "over the next 30 days" between E.U. and U.S. trade officials. He stressed that the U.S. Department of Trade has the lead role in the negotiations over hormone-treated beef. The U.S. plans to impose 100% import tariffs on a range of E.U. exports worth $900 million a year from Aug. 2 in retaliation against the E.U.'s 10-year old ban on imports of hormone-treated beef. The U.S. beef industry claims the ban has deprived it of $250 million a year in export revenues.

The E.U. refuses to lift the ban on the grounds that, according to E.U. scientific committee findings, hormone-treated beef increases the risk of cancer in humans, and has ignored three separate rulings from the World Trade Organization instructing it to repeal the embargo. Before Glickman and Fischler's meeting Thursday, both sides signaled that they were willing to discuss a settlement under which the E.U. would make agricultural trade concessions to the U.S. in return for being allowed to maintain its ban.

In the event, no such settlement emerged. "We didn't go into specifics. No formal compensation proposal was presented," Glickman told reporters. "We need signals over what form of compensation the E.U. is considering." He added that the U.S. will proceed with its plans to impose punitive import tariffs on E.U. goods, while stressing that the search for an amicable solution will continue. "We agreed to continue discussions while recognizing that the U.S. will continue to protect its interests," he said. "But it is also in our interests to defuse the dispute. We want peace, but not at any price."

He wouldn't say whether the U.S. will continue to press the E.U. to set a date for the lifting of the ban, a demand that Fischler rejected Wednesday, saying, "We can't negotiate under that condition." After the talks Thursday, Fischler also committed himself to finding a compromise solution to the dispute, and hinted that compensatory trade concessions by the E.U. offer the best chance of a deal. "We will try to get a solution before the U.S. imposes import tariffs. It's not in our interests to end up in a trade war. Beef is not a large part of E.U.-U.S. trade as a whole," he said.

He added that "various options" for E.U. compensatory trade concessions were discussed, but stressed that the talks were "not a negotiating round." "We are neither closer nor further away from a solution," he said.

Fischler told reporters Thursday that Glickman agreed to bring inspection procedures at U.S. slaughterhouses handling exports of hormone-free beef to the E.U. into line with E.U. norms. "The U.S. will take appropriate steps before 15 June," he said. The E.U. last month said it would withdraw the approved status of a handful of U.S. abattoirs handling exports of U.S. hormone-free beef, worth some $20 million a year, from June 15 unless they agree to tighten up their carcass inspection procedures.

The move came after E.U. inspectors found high levels of antibiotic and hormone residues in a shipment of supposedly hormone-free beef.

Welsh Assembly could lift beef ban next week

PA News Thu, May 20, 1999 By Brendan Berr
The Welsh Assembly is likely to vote next week on whether to lift the beef-on-the-bone ban. If approved, the move could lead to the controversial regulation being scrapped in Wales from July, when the Assembly officially takes over power from the Welsh Office. Liberal Democrats today won a ballot among members which allowed them to set up the first Assembly debate on the issue on Tuesday.

Kirsty Williams, Lib Dem AM for Brecon and Radnor, said she expected a vote to be won overwhelmingly. Conservatives and Plaid Cymru are both on record as favouring a lifting of the ban as soon as possible. Labour is three members short of a majority in the 60-seat chamber and, according to the Lib Dems, a few Labour members could decide to vote with opposition parties to show their support for struggling farming communities.

"By lifting the ban, the Assembly will be demonstrating its confidence in the Welsh livestock industry," said Ms Williams. "It will also be returning trust to the people of Wales who are more than capable of making their own informed choices about what they should eat." An Assembly vote to lift the ban could put pressure on Agriculture Minister Nick Brown to cancel the measure in England at the same time.

Welsh Labour leader Alun Michael has declared himself in favour of an early lifting of the ban - but he has warned the Assembly that it must consider carefully all the latest scientific evidence on BSE before doing so.

20 cases of BSE on organic farms: chicken manure?

Inquiry statement of Harash Narang
"1. 20 BSE cases have appeared on some organic farms where the animals have not been fed with MBM including the farm owned by Jeff Nichols. This led to the belief that organophosphates might be responsible for BSE. However, I have discussed this phenomenon with three organic farmers and I visited several organic farms during 1994. I established that the cows on the farm had been exposed to and had eaten poultry manure, which is widely used on organic farms. I have personally witnessed cows eating poultry manure from a heap of manure waiting to be spread on an organic farm. It is also an established practice to add bird droppings into some cattle feed. Since MAFF allowed poultry to be fed on meat and bone meal until 1996, the poultry droppings would contain large amounts of the undigested agent.

2.16 If random testing had been started when I suggested it we would have been able to discover the true extent of the disease and it could have been eradicated. In a study undertaken for "World in Action" in 1995 World in Action obtained 30 cattle heads from abattoirs in the Midlands. I tested 28 brains and established that 8 of the cattle tested which must have appeared healthy at slaughter, actually had BSE. This BSE would be detected by my test even though they were sub-clinical, symptom free cases. To date, MAFF has no such test of its own and vacuoles are not seen in sub-clinical cases until they develop the clinical symptoms.

2.30 I explained to Mr Ray Bradley at MAFF (MAFF's BSE research co-ordinator) that the touch test which I had developed in the USA would not only help to remove affected cattle from the human food chain, but would also show the percentage of animals affected and which farms they came from. If BSE affected farms could be identified, these animals and those affected farms could be isolated. Cattle from those farms should not be used for breeding purposes and this would help in eradicating the disease.

2.31 However MAFF did not want to know. Mr Bradley told me in January 1990 that BSE was like scrapie in sheep. He said that there was no risk to humans. It was a dead-end disease as far as cattle were concerned. He told me that my test was very sensitive and that the Minister was fully aware that affected cattle were going through the abattoirs. He told me that my test was too sensitive and that the Minister did not want my rubber stamp merely to prove that they were affected. When I suggested that we might do the study privately for our own knowledge to find out what percentage of animals were infected if any, he told me that results eventually would become public knowledge and this would cause a big headache for MAFF and the Government.

2.60 The PHLS also discovered during the investigations (but took no further) the following:-

i. That one of the interviewees who had died from CJD had during his life often chopped bulls heads to feed his dogs.

ii. That the husband of a woman who died of CJD had told me that he worked in a cattle auction and that he had regularly witnessed cattle with clinical symptoms of BSE being sold in auction.

iii. That a butcher whose wife had died of CJD had told me that his wife had helped to kill animals with BSE symptoms in his back yard and that these animals had been sold for consumption.

2.70 At about this time at a meeting with Mr Amman a farmer in Kent I was informed when discussing how BSE had affected his herd that he had regularly found large bones buried in feed grain supplied to him. On enquiry he discovered that the same container lorries were being used to transport both feed grain and bones. He also told me that he frequently identified progeny of BSE cattle to MAFF vets, but MAFF were not prepared to accept his evidence of vertical transmission. He is very critical of his dealings with MAFF and their reluctance on one occasion to accept that one of his cows had BSE.

4.20 Since the emergence of BSE, similar SE's have been diagnosed in domestic cats and captive wild animals at several zoological collections in the British Isles (BSE in Great Britain, a Progress Report, May 1996)."

FDA Warns About Dialysis Blood

Wed, May 12, 1999 By Arthur H. Rotstein  Associated Press Writer
TUCSON -- The Food and Drug Administration has issued a safety alert over dialysis equipment that may have exposed patients to each others' blood and their blood-borne diseases. Small amounts of blood that leaked inside dialysis machines have been found at treatment centers in Arizona, Florida, New Jersey and Pennsylvania, the FDA said Tuesday.

The risk that patients were exposed to others' blood and thus to blood-borne diseases such as hepatitis or HIV, the virus that causes AIDS, is "extremely remote," said Steven Niedelman, an enforcement director for the FDA's Center for Medical Devices and Radiological Health. [Why is risk remote? -- webmaster]

The machines are used to cleanse the blood of deadly toxins when the kidneys fail. But Niedelman said there is concern because traces of blood were found in tubing inside the machines. Filters are supposed to prevent that from happening. "We don't really know the extent of the problem or what's causing the problem, so it's really a concern to us," he said.

The manufacturer of the tubing, Miami-based Nissho Nipro Corp. Ltd., told the FDA on Friday it is voluntarily recalling 154,000 sets as a precaution. The company has distributed 2.1 million tubing sets in the United States during the past year. Last month, officials at St. Mary's Hospital in Tucson said that 121 kidney dialysis patients faced months of blood tests to determine whether they were exposed to blood of other patients.

Since December, there also have been incidents of blood contamination of dialysis equipment at Total Renal Care, a dialysis center in Miami Lakes, Fla.; Lee Regional Hospital in Johnstown, Pa., and Bayonne Hospital in Bayonne, N.J., the FDA said. The alert advises facilities to inspect their machines, and if contamination is found, to disinfect them.

BSE - The Untold Story

BBC Radio: Thu, May 20, 1999, 11:36 AM
There have been no cases of BSE - bovine spongiform encephalopathy, or "mad cow disease" - in North America. But a BBC programme says some experts fear a new kind of Creutzfeld-Jakob Disease (CJD), the human equivalent of BSE, is killing young Americans. The programme, "BSE - The Untold Story", was broadcast on Radio 4.

CJD is normally a disease of elderly people, but the type linked to eating the meat of BSE cattle - new variant CJD - attacks young patients. CJD is not a notifiable disease in the USA, so there are no accurate figures on the number of cases or the ages of patients. A Washington lawyer, Andrew Kimbrell, told the programme: " We've seen explosions of cases. We're facing what the UK faced a few years ago". "Is it a time bomb? Is it just something that a few people seem susceptible to?"

US supplies thought safe

Mr Kimbrell wants an investigation into the possibility that the country's blood supply may be infected with CJD. Britain started importing blood plasma from the US last week, because of "the theoretical risk" that CJD could be spread by infected British blood supplies. The programme says there is a serious body of scientific opinion which believes that BSE infected people, in its CJD form, not through the stomach but through the bloodstream.

A zoologist, June Goodfield, says that if eating meat caused infection by CJD, there would have been many more cases by now. The programme cites earlier studies of the Fore tribe in Papua New Guinea, who suffered from a similar brain disease called kuru. These studies suggested the disease was spread when people handled the flesh of kuru victims, rather than when they ate it. They suggested the infectious agent could enter the bloodstream through cuts and bites, or through mucous membranes.

Professor Sir John Pattison, who chairs the Spongiform Encephalopathy Advisory Committee, told the programme he had no evidence of a new CJD strain in the USA. The programme also says it has seen estimates of the likely number of British CJD victims, which were prepared for the Royal Society. These say there could be as few as a dozen more deaths, or as many as thirteen million.

The U.S.-European Beef Dispute Heats Up

Mon, May 17, 1999 Reuters Online Service By David Evans
BRUSSELS - European Union farm ministers Monday backed the European Commission's stance in its dispute with the United States over hormone-treated beef but warned against any escalation into a full-blown trade war.

"There is a clear indication there is a health risk. We can only avoid an escalation in the dispute if we discuss the findings of the scientific opinion," German Farm Minister Karl-Heinz Funke told a press conference. Ministers wrapped up their meeting well ahead of schedule, with landmark reforms to the $50 billion a year Common Agricultural Policy agreed in March formally adopted without discussion.

The row over the EU's import block on beef from cattle treated with hormones has brought a U.S. threat of punitive duties of $202 million on goods as diverse as mineral water and motorcycles. Ministers, finding themselves on the brink of another trade dispute so soon after the battle over bananas, called for more dialogue and for transatlantic trade friction to ease.

"It is my very strong view the decision should be based on science and we should be talking it through with the Americans," Britain's Nick Brown told reporters. "No one wants another trade war." Europe's acting Farm Commissioner Franz Fischler has vowed to challenge the threat at the World Trade Organization and will take an EU offer of interim compensation for the United States to a meeting with U.S. Agriculture Secretary Dan Glickman in Dublin Wednesday and Thursday.

Fischler Monday defended a decision not to lift the ban by last Thursday's WTO-inspired deadline because of fresh scientific evidence which pinpointed possible health risks. "We are considering compensation to avoid the United States and Canada taking retaliatory measures," he said. "We should not talk about a trade war nor wage one." "But there is new scientific evidence available...both sides must realize there are serious concerns and we have a new basis for discussion."

The original WTO deadline of May 13 was interpreted differently by both sides. The United States demanded the embargo be lifted by then, but the EU said the rule only required it to produce an assessment of the health risks.

The hotly contested EU scientific report, which said a hormone used by the U.S. cattle industry could be carcinogenic, prompted the Commission to rule out lifting the ban. Fischler also ruled out allowing U.S. beef into EU markets under a strict labeling scheme as a potential compromise. "If there is clear risk to human health then labeling cannot be considered," he said.

That would leave the EU offering Washington compensation through greater market access for other U.S. goods, possibly including hormone-free beef. But it believes the United States has overestimated the damage done to its cattle industry by the decade-old ban.

Fischler's spokesman Gerry Kiely told journalists Monday that when the EU first applied the embargo in 1989, Washington imposed $100 million dollars in unilateral sanctions. However since then U.S. exports of hormone-free beef had increased.

Scientists to test if beef is the cause of CJD

May 18 1999 by Valerie Elliott, Consumer Editor  L. Times
Two scientists who believe that BSE is caused by a common microbe found in muddy water, sewage, soil and human skin have been given L216,000 by the Ministry of Agriculture to prove that beef is safe to eat.

If their theory is right, more than 3.5 billion pounds has been wasted in measures to protect public health from contaminated beef and herds of cattle have been slaughtered pointlessly.

Alan Ebringer, Professor of Immunology at King's College, London, and Professor John Pirt, an expert on the role of bacteria in diseases, believe that the microbe acinetobacter is the link between BSE and the new-variant Creutzfeldt-Jakob disease and that it is not spread by eating beef. Dr Ebringer said that acinetobacter was so common that it might explain CJD in farmers and vegetarians.

The scientists have been given permission to conduct two more years of research. The ministry said that the sum was a tiny proportion of the L13 million spent on BSE research. "Awarding the grant does not mean we are convinced by the arguments, but we are keen to consider alternative theories," a spokesman said.

The theory is controversial because it challenges the scientific establishment in Britain, which believes that BSE is caused by a a rogue prion protein. First advanced by Professor Stanley Prusiner, of the University of California, it is now almost widely accepted.

Burning cattle believed to be the cause of CJD

Daily News 18 May 99 Michael Hanlon 
THE human form of mad cow disease is probably curable and has nothing to do with infected beef, according to one of Britain's leading scientists. ...

Forty-five people have contracted so-called new-variant CJD in Britain and 39 of these have died. Current medical practice is to treat the symptoms with antidepressants and other drugs, but the disease is assumed to be incurable. ...

In 1997, Stanley Prusiner, an American scientist, won the Nobel Prize in medicine for his work on prions - proteins which he said caused both BSE in cattle and the brain-wasting disease CJD in humans - a theory that Prof Ebringer rejects as "totally implausible". ...

Prof Ebringer says that the symptoms of multiple sclerosis, which include psychiatric disturbances, memory loss and "spongy" brain degeneration, are so similar to CJD that the two conditions are probably the same "autoimmune" disease. ...

HE said that CJD patients should be treated with large doses of antibiotics, plus drainage of body cavities like the sinuses where the bacteria are likely to be concentrated ...

"I never stopped eating beef because I knew it was nonsense from the beginning," said Ebringer. "There's going to be no plague of CJD."

Comment (webmaster): The original press release claims fantastic results for a study not even begun. This is a good example of a squeeky wheel proposal that gets funded while many sounder proposals go begging. For example, the sequence of the promoter region of the prion gene in sporadic CJD or the nature of the covalent arginines on the prion protein could be determined for a fraction of this grant. While there is no great harm in allocating a small sum for a study unless it is to the exclusion of better proposals, the authors have demonstratred in their Inquiry statement a profound unfamiliarity with the 6,000 paper scientific literature. The thesis advocated here has few prospects for making any contribution to our understanding of these diseases.

Comment (Herbert Budka, M.D.):

"I normally keep out of such discussions, but here my anger gets that great that I must pull the plug. I cannot agree that they should get their grant "on the principle of leave no stone unturned". This is, in my understanding, still a scientific grant. I have seen a lot of much more reasonable projects left unfunded because of simple lack of money. My conclusion is, and it is corroborated by your comment, that the grant was awarded not for scientific but for political reasons. Shame on the (probably scientific) body which awarded it."
Professor of Clinical Neuropathology
Institute of Neurology, University of Vienna,
AKH 04J, POB 48, A-1097 Wien, Austria.
Phone: +43-1-40400-5504, -5501, -5573;
FAX: +43-1-40400-5511, -5573.
 

Comment (J Ralph Blanchfield, MBE):

"I am sceptical about the validity of the case they put forward; unimpressed by the way in which they put it forward; and critical of the way that they appear to ignore or dismiss established facts and published research findings with which their conjecture is incompatible, some of which Roland has already pointed out, and the way in which they _know_ the outcome of their project before having carried it out. ['Prof Ebringer said yesterday: "If our theory is right, and we are confident it is...." ' (press report of 17 May). 'The autoimmune theory cannot be overthrown. The prion establishment, of course, is reluctant to admit the validity of the autoimmune theory. However, we take comfort in the fact that the truth will out.' (Pirt, letter 30 March 1999) ]."
Food Science, Food Technology & Food Law Consultant
Chair, IFST External Affairs
Web Editor, Institute of Food Science & Technology

CWD in Oregon: worried hunters

15 May 1999 Eugene Register Guard sports page, webmastor letter to newspaper
"Dear Mike Stahlberg, tel 541-338-2332

In your Register Guard column of 13 May 99, you wrote that "last year a deer with similar symptoms [patches of missing hair and poor condition in Tillamook, south Willamette valley, and Washington State] was evaluated at Oregon State University's Veterinary Laboratory. Tests ruled out the presence of CWD but indicated the deer carried several internal parasites plus large numbers of lice on its skin...." according to a 12 April 99 ODFW press release.

Could you possibly provide me with the name and contact information for the veterinary pathologist who performed the study? I would like to examine the neuropathology slides myself under the state public records law if need be.

ODFW's public information officer in Corvallis, Pat Wray, says the tests were performed by :

Pathologist Report:
Amir N. Hamir, BVSc, PhD
Associate Professor and Pathologist Phone: (541) 737-6963 
Final Report Date 2/11/98
Accession Number D98-07003 [off-line]

[Dr. Hamir  moved from OSU to NADC, Ames, IA in August 1998 and does not recall details of the case in question. However, he is sure that the negative test for CWD was based on histopathology only. The post mortem report, H&E glass slides, blocks of tissues, (and in some cases the formalin-fixed tissues) would normally be available  at the OSU facility (Veterinary Diagnostic Laboratory, Magruder Hall, Corvallis, OR 97331). The Acting Director, Dr. Jerry R. Heidel (541-737-3261) would be the person to contact for obtaining them.]
 
Virology Report
Rocky Baker Phone: 541-737-2172
2/5/98
 
Microbiology Report
Robert Sonn Phone: 541-737-6823
2/5/98
 
Be aware that a single black-tailed deer from Oregon was in fact confirmed as positive for CWD some years back. However, this animal was quartered for nutritional studies at the DoW's Foothills Research Station in Ft. Collins, Colorado (the global epicenter of CWD) and may (or may not) have acquired the disease in Colorado. I have not been able to learn the age of the deer at the time of its export to Colorado or its age at death. You might give the Colorado guy a call, Mike Miller, (970) 472-4348. [He will otherwise put a happy face on CWD for you -- 51% of their budget is elk and deer tags, predominantly out of state, according to their web site.]

There would be no credibility whatsoever to the report from Oregon State University's Veterinary Laboratory unless the most sensitive modern methods were used. While certainly well-intentioned, the veterinary pathologists there have likely never seen a case. The best method is to take the obex of the medulla oblongata from the deer and stain with a cocktial of monoclonal prion antibodies (called immunohistochemistry). Simply looking for spongiform plaque would miss a large proportion of the cases, especially those in early and middle stages. Most states are doing samples of 300-400 deer, not single individuals. This is not a disease that ag schools are eager to find because of the implications for their support from sheep producers.

I am strongly opposed to local testing for CWD because of unavoidable conflicts or perception of conflicts in states where fish and game derives a large proportion of its operating budget from game tag sales etc. for the ag schools. Properly collected samples are better sent (by prior arrangement) Dr. J Miller at the federal facility in Iowa or to Dr. E. Williams at UW in Laramie, Wyoming.

The main risk factors for CWD in Oregon would be:

(1) horizontal transmission from sheep infected with scrapie, another prion disease. This disease has been endemic in the Willamette Valley for decades; the percent infected is not known due to resistance from growers to systematic surveys [Oregon scrapie update: Dr. K O'Rourke, WSU]. Deer at the Colorado facility were co-housed with sheep and put on former sheep pasture -- this is by far the most plausible scenario for the original crossing of the species barrier. Indeed Dr. Stone told me that he and coworkers assumed the first cases were scrapie back in 1967. Sheep pasture here in Oregon is not fenced to exclude deer.

Because there appear to be four or more strains of scrapie in the US based on incubation period clusters found by Cutlipp et al., the symptoms of CWD might vary considerably from what is seen in Colorado, depending on what strains are prevalent in Willamette Valley sheep. Hair loss is not unusual in TSE generally and could arise from animals scraping themselves to relieve a neurologically based itch. Ataxia and gait disturbances might not be seen if the deer are simply dying off fairly rapidly in the woods by this stage in disease progression.

(2) Importation of animals from endemic areas. Typically, this has meant elk game farms (which Oregon may still lack) or other captive game facilities. These facilities swap animals around like baseball cards. Colorado took surplus research animals and sold them to zoos and game farms where they later exhibited disease. In one case, animals were shipped to South Dakota where they subsequently infected wild deer across a fence line according to state vet Dr. Sam Holland. Colorado also released infected animals into the wild. The level in wild deer in Larimer County reached 6% in 1998; a number that is limited on the low side by the ability to detect infection early on.

(3) Horizontal transfer of BSE from infected zoo animals. It now seems that a very significant proportion of zoo animals in Britain and France may be incubating bovine spongiform encephalopathy. These animals were fed dairy cow rations during the height of the BSE epidemic (or split spinal cords from cattle to the large felids). Thousands of exposed animals were imported to facilities in the US during the 1980-1999 period. As a purely speculative example, an infected cheetah is imported by the safari park in Winston, Oregon from the Marwell Zoo in the UK. This animal then infects others at the facility and eventually wild animals adjacent to the facility.

(4) TSE may arise in any species of mammal from mutations in their prion gene. In humans, 20 different mutations are known for the chromosome 20 gene. The rate is usually taken as one per million. Without knowing the deer population in Oregon, I would guess this means a few deer per decade. In this scenario, the genetically infected deer passes it on horizontally to normal deer and the epidemic sustains itself in this way. Crowding on wintering grounds is suspected in Colorado of fostering transmission.

I would not be too quick to pooh-pooh the possibility of CWD in Oregon and its potential risks to hunters. A human-interest columnist of your newspaper wrote an awful column this week, saying CJD was not an infectious disease. Actually, it is extremely infectious, untreatable, and invariably fatal. There is no information whatsoever available on the risk of CWD to humans (few people volunteer for lethal dementia trials) though an "experiment" is now underway on humans in NE Colorado. The main route of exposure of humans is probably deer or elk spinal cord. Animals are pooled at the game processor and infectious material may show up in sausage, if not from your deer, then from the other guy's. Nebraska fish and game provides a neck roast recipe on their web site.

The main two games people in the business play on reporters is to say, 'hey I hunt there myself and I feel great' or 'there is no evidence that CWD transmits to humans.' True enough, but there is equally no evidence that it doesn't: no studies have ever been published (or even started). Absence of evidence is not evidence of absence. This disease can kick in after a 40 year incubation period.

What I do is simply bring a pepperoni sausage to scientific meetings, tell colleagues that it is elk sausage made from a confirmed CWD case, and ask the fish and game guys if they will eat (or touch) a slice in front of me. I have learned a lot more from this than from their press packets.

http://www.mad-cow.org/99feb_cwd_special.html is a resource on CWD that I put together last year as part of a much larger ongoing spongiform encephalopathy project.

As noted, I have no opinion on whether CWD is present or not in symptomatic deer in Oregon and Washington. A much larger study using the best available methods is needed given likely exposure to scrapie sheep."

CEAH Meeting Minutes 11 July 1995

FOIA documents obtained in May 1999
"Mike Miller, Tom Thorne, and Beth Williams also commented on the rendering of Cervidae. A small amount (10-25% of hunted animals) of rendering of free-ranging cervidae is conducted. Rendering is performed by 'game Processors.' Game processors will take meat trimmings, blood-shot meat and bone from the hunters, but will not take heads,hides or hooves. The heads and gut pile are normally left by the hunters at the site of the shooting, but if offal is submitted it is taken to a landfill. Heads are occasionally taken to the taxidermist or to game authorities to establishe the species, size, and sex of the animals. The brains are not rendered and are placed in a landfill. Along the Front Range of the Rocky Mountains where CWD does not exist [sic], about 15,000 pounds per week are submitted to game processors."

"Regarding rendering of Cervidae in wildlife facilitiess, prior to 1985, dead Cervidae were taken away by private workers, but were not rendered as far as is known [who employed the private workers?]. From `1985 to the present, when Mke Miller began his position with the Colorado Division of Wildlife, all dead Cervidae (with or withouth CWD) are taken to landfills or incinerated by facility personnel only. There is no rendering of Cervidae carcases from Colorado and Wyoing research and diagnostic facilities." [Why bother with these precautions if Miller really believes CWD presents no risk to humans or livestock?]

"Regarding movement controls in Colorado and Wyoming, no movement of live Cervidae is permitted from affected counties [sic], and there is no release of wildlife facility animals into the wild or to zoos. Rendering of free-ranging Cervidae from Wyoming counties (affected or non-affected with CWD) does not occur [sic] due to the lack of renderers in Wyoming."

Eugene, Oregon cluster

16 May 99 webmaster
Eugene, Oregon is awash in rumors about unexplained cases of CJD. A45 year old blood donor died of CJD on Saturday [Judith Willig case, [Dr. Haleigh Warner]. There was no recall or notification on the blood which her sister said had been donated in fall, 1998. Biohazard bags were put in the hallway and another patient moved in to share the room for the last few days. Brain tissue was saved but probably not tonsil or GI tract; the victim has already been cremated. Histopathology at UW was excellent and included GFAP, H&E, and congo red. The brain was sent to the Gambetti lab for further studies.

A British woman, age unreported, is also said to have been diagnosed with CJD in the same hospital (Sacred Heart). This could be the first case of nvCJD in the US. It is not known whether she was a blood donor. This follows the death of a 69 year old woman in nearby Cottage Grove in Dec 98 [Dr. Doan] and a unverified CJD death around the same period in nearby Roseburg as well as a confirmed case in an 89 year old man in Coos Bay.

A 14 year old boy is supposedly also in the local hospice with confirmed CJD. This is improbable as it would be the youngest case ever reported. A saliva-spewing oncologist is said to have shouted down hospice workers concerned about protocols and exposure of personnel.

The population of Lane County, Oregon is 250,000 (so the expected one case per 4 years is off by a factor of 20). The local paper bungled the story badly on t he first go-round, omitting all but the Judith Willig case, writing:

Teacher, hero one in million

By KAREN McCOWAN Columnist, The Register-Guard
May 10, 1999
"The rareness of her illness brought Judith Willig to my attention. "One in a million," Eugene neurologist Robert Tearse calls it...I heard rumors of her illness even before her friends contacted me. Several readers called to ask if a local woman had been diagnosed with Mad Cow Disease.

"To the ignorant, I suppose the answer would be `yes,' " Tearse said. "But Mad Cow Disease is a disease of cows, not people." [sic] A similar condition in humans is called Jacob-Creutzfeldt Disease. Both diseases are caused by an abnormal protein. Both destroy nerve cells throughout the brain, leaving spongelike holes.

"In cattle, however, the disease spreads by ingestion. Despite tabloid headlines and an infamous "Oprah" episode, there is no evidence [sic] Mad Cow Disease has ever been transmitted to humans, through meat consumption or otherwise. The cause of Jacob-Creutzfeldt is unknown.[sic]"

"It is not considered contagious." [The paper printed a retraction on 19 May 99. The second article makes clear that the neurologist stated that the disease was in fact contagious. -- webmaster]

Tigard, Marion County:

"Female, 65, died November 7, 1998, 3 weeks after diagnosis. She was a homemaker, mother and grandma. She was from the UK and went back periodically after migrating to the states forty years ago. She went back for several months four years ago to care for her mother-in-law. The Hospice nurse stated that she was the third case he had treated for CJD."

Comment (webmaster): This case should have been studied for nvCJD but apparently was not. :

Lane County, Oregon

"Female, age 57 passed away after an illness of one year, on December 28, 1986. She was a retired school secretary. She was born in B.C. Canada, moved to Oregon in 1968, travelled around the world several times. Lived in Africa, Saudi Arabia, Egypt, and Caribbean. Her surgeries were: Gallbladder surgery in the 1950's and very little dental work was ever done. She was taken to Loma Linda Hospital in April of 1986, after Oregon Doctors couldn't figure out what was wrong. After several tests done, and talked to Dr. Massa the diagnosis was given to the family that she had CJD."

Cases kindly provided by CJD Watch.

Officials find no proof of brain disease epidemic

Tuesday, June 1, 1999 OregonianDebra Gwartney, Correspondent, The Oregonian at 541-342-7797 and Patrick O'Neill Lane County reports two fatal cases of Creutzfeldt-Jakob disease, but health leaders say outbreak fears are unfounded State and local officials say they have carefully investigated a stream of rumors about the spread of a rare and transmissible brain disease, which caused the death of a Leaburg woman last month, and have not found cause for alarm.

"I'm not finding an epidemic, but many people are concerned," said Dr. Sarah Hendrickson, Lane County's medical officer. Hendrickson said she believes concerns about a local cluster of the disease in Lane County are overblown.

Judith Willig, 45, died on May 8 of Creutzfeldt-Jakob disease, which is challenging to diagnose and always fatal. Soon after Willig's death, health officials began to hear concerns that the disease had spread.

"We have had many phone calls about it," said Dr. Paul Cieslak, manager of the communicable disease department of the Oregon Health Division. "And the (federal) Centers for Disease Control even had some calls from people wondering if they were checking out all those cases of CJD in Oregon." Cieslak said his office is checking out all leads it receives and so far has found no new cases of CJD in the county.

Hendrickson said her review of hospital reports and death certificates has confirmed two CJD deaths in Lane County so far in the year: a woman in her 60s from Cottage Grove and Willig from Leaburg. A sense of alarm about the disease may have been set off, Hendrickson said, because of CJD's faint link to bovine spongiform encephalopathy, or "mad cow disease." "But Judith Willig did not have 'mad cow,' " she said.

Both CJD and mad cow disease are strains of prion diseases, maladies caused from infectious protein particles in the brain that lead to the development of small pin-prick-size holes in brain tissue. The diseases cause loss of coordination, failing eyesight and profound dementia. Death is certain, usually no longer than a year after the first symptoms present themselves.

However, classic CJD, first detected in humans more than 80 years ago, is markedly different from the strain of the disease that struck cattle in Britain and caused the government to order the slaughter of thousands of cows in the mid-1980s. Nothing similar has turned up in American beef.

Classic CJD most commonly afflicts people older than 60 and can have an incubation period of 30 years, according to the federal Food and Drug Administration. Some victims have a family history of the disease, while others are accidentally infected through medical means, such as receiving infected corneal transplants or being treated with infected brain electrodes, according to the FDA.

What has some people worried is the confirmation of a new strain of CJD, called "new variant CJD," which has caused the death of more than 40 people worldwide. Directly linked to mad cow disease because several victims worked in slaughter houses or butcher shops, the new variant strain has not been found in the United States.

Officials concerned about keeping the new strain out of the country have banned the importation of British beef. And the FDA will hold public hearings, beginning Wednesday, on whether to prohibit blood donations from anyone who has spent more than six months in Great Britain from 1980 through 1999.

Last month, the Canadian government officially established similar guidelines for blood donations. One common sign of the new variant strain has been the young age of the victims. Most have been in their 20s and 30s at the time of death, according to Cieslak.

Because of Willig's age, her loved ones worried that she may have been the first to contract the new variant strain. But a brain biopsy, performed at the University of Washington several weeks before her death, determined that Willig suffered from classic CJD, Hendrickson said. Further studies expected Willig's brain will be further studied by pathologists at the University of Indiana as part of a federal study on aging, Hendrickson said.

Willig's partner, Kathryn Albere, said she and Willig's many devoted friends hope that examination will lead to an explanation of how the woman contracted the disease. Willig loved to eat wild meat and often dined on elk and deer. She was an avid gardener and spread "sacks and sacks of bone meal on the ground without wearing a mask," according to Albere. Willig worked as an anthropologist and spent long days in the field digging in the earth for artifacts and bones. She underwent knee surgery several years ago.

Could any of those activities have harbored the CJD infection? "Judith was strong and robust. She was a brilliant intellectual," said Albere. "We would all like to know how this happened."

According to the FDA, CJD affects about one in a million people in the country each year, which would mean an expected 2.5 deaths in Oregon annually from the disease. Cieslak headed up a five-year search for CJD victims in Oregon from 1990 through 1995, as part of a federal study of the disease. He said his office found evidence that five people in the state died of the disease in each of those years. [makilng this 2 per million per year -- double the alleged rate (webmaster)] That concerted search, which included calls to every neurologist in the state, ended nearly four years ago, but Cieslak is confident that the average number of CJD deaths has remained steady.

Illness under-reported

But Eugene biochemist Tom Pringle, who has long been involved with CJD issues, said he thinks the disease is seriously under-reported. "Hospitals don't want the nursing homes where they send these people to get alarmed about a possible infectious disease, so they call it Alzheimer's," Pringle said. "Then it goes down on the death certificate as Alzheimer's."

Two recent medical studies, one from Yale Medical Center and the other from the Department of Neurology at the Veterans Affairs Medical Center in Pittsburgh, present evidence suggesting that up to 7 percent of people diagnosed with Alzheimer's disease actually succumbed to CJD. The studies suggest that when an elderly person displays signs of dementia, Alzheimer's is an obvious diagnosis. Brain biopsies are rarely performed, and neurologists who can easily spot CJD often are not consulted.

According to the state's Center for Health Statistics, Oregon has the third-highest Alzheimer's disease death rate in the nation, with more than 500 people dying from the disease annually. Hendrickson said she thinks it's a real possibility that CJD is under-reported and is often mistaken for Alzheimer's disease.

"CJD is one of those dementias that is often misdiagnosed or undiagnosed," she said. Hendrickson said she's anxious to hear from anyone in Lane County who believes a family member died of CJD. Tel 541-682-3956, fax 541-682-2455 fx

Pringle said he will continue to push for more careful scrutiny of the many uses of cattle derivatives, including vitamins, cosmetics, photographic film and other products, for possible new variant infection. "But by the time it hits the population, it'll be too late," he said.

Huge number of phone calls follow story

2 June 1999 Debra Gwartney, Oregonian reporter "I wanted to let you know, near the end of the day here, that I received an utter onslaught of communication today. Two I thought you'd be particularly interested in. A woman named Stephanie Fry called to say that her mother is dying from CJD, and is in a nursing home in Salem. Mother lived for many years on the McKenzie River, not far from where Judith Willig lived.

This afternoon, a woman from Coos Bay called to say one of her co-workers at Roseburg Lumber died of CJD last Thursday, and was cremated Sunday. His name was Benjamin Gulpan, age 62. Lived in Coos Bay most of his adult life, grew up in Hawaii. Native Hawaiian father. About ten years ago, he had brain surgery in Coos Bay for benign tumors. The woman who called me can be reached be email. She said many people in the mill are quite frightened, as Gulpen was at work and fine 8 weeks ago."

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