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Page 22, line 22: “I was not worried about sort of any confidence being broken because I felt it was all being done within a confidential”. Line 25: “It had decided and sent to him with the explicit statement”. Page 23, line 1: “but there is was no harm in his knowing about where we have had got to” snip... " The transcript, page 111 lines 23 et seq, deals with my response to a question from Professor Ferguson-Smith. In responding to that question I used the word "peripheral" in the colloquial sense meaning "at the extremities" and had in mind muscle meat. To a clinician or pathologist, peripheral nerves are those outside the central nervous system (CNS). Meat, as cut from a body, contains muscle fibres but also fibrous tissue, vascular components and nervous components such as afferent and motor nerves and nerve endings. Previous studies by Hadlow et al on scrapie in sheep (1982) and goats are summarised in the SEAC report of 1995 on transmissible spongiform encephalopathies which was entitled "A Summary of Present Knowledge and Research". The reference appears in Table 5.2 page 65 of that report. I also had in mind the systematic studies on experimental scrapie in mice by Kimberlin and Walker reported in papers such as "Pathogenesis of mouse scrapie. Evidence for spread of infection from central to peripheral nervous system" J. general Virology (1983) 64, 713 -716 and "Pathogenesis of Scrapie in Mice after intra-gastric infection" Virus research (1989) 12,213 -220.These report the amounts of infectivity in different tissues in sick animals and before disease appeared. In particular, there was none in muscle. In 1990, I therefore assumed that there would be less infectivity in apparently healthy cattle than in those that were sick. In 1990 SEAC members similarly assumed that there would be even less infectivity in the nerve roots (and the dorsal root ganglia mentioned by Professor Ferguson-Smith) ithan in the CNS and still less in the more distant peripheral nerves. They had no knowledge of the variations in the amount of infectivity at different times as the disease spread through an animal and, in particular, at different points in the peripheral nervous system of cattle." http://www.bseinquiry.gov.uk/files/ws/s011d.pdf (we now know that the TSE agent has been documented in muscle tissue and other tissues besides the CNS in many species. ...TSS) http://www.bseinquiry.gov.uk/files/yb/1987/06/04001001.pdf http://www.bseinquiry.gov.uk/files/yb/1987/07/10002001.pdf IN CONFIDENCE http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf http://www.bseinquiry.gov.uk/files/yb/1988/12/31001001.pdf 18. Following the conference, we prepared the full paper we had presented, for publication in a book of this European Commission-sponsored conference and sent it to our superiors for approval. (The correspondence which ensued in April and May 1991 is found at YB91/4.16/1.1;YB91/4.22/2.1;YB91/4.30/1.1;YB91/5.3/3.1). Specifically, despite detailed arguments supporting our statements, the following ultimatum was faxed to us from the then Assistant Chief Veterinary Officer, making it plain that he was taking into account the views of the then CVO: “We are not willing for the paper to be published unless these references are removed. This may be unacceptable to the authors, in which case permission to publish is refused.” 19. Despite protestations that the body of the text would no longer agree with the already published abstract, and our detailed knowledge on the subject notwithstanding, the edict stood. We were left with little alternative but to amend the paper, which by this time had missed the original deadline for submission and was in danger of not being published at all (see correspondence above). 20. Subsequent to its publication in the conference book (ref 5), the paper was also published in a refereed journal (ref 7). The original abstract from ref 5 was then also altered to agree with the altered text. Specifically the words “with BSE” were removed from the phrase “epidemiological association with BSE”. I had left MAFF before this paper was ever published. 21. This episode was described in Dispatches (Channel 4, 9pm Thursday 11th December 1997), and on two separate occasions in. The Independent newspaper (YB97/12.11/1.1 and YB98/1.26/1.1). Outright rejection of manuscripts submitted for publication, during "Refereeing/Scrutineering" by Journals 22. The peer review system is in itself generally reasonable. However, an issue of real concern is that the Veterinary Record , the main channel of information for the veterinary profession, failed to provide an open forum for discussion of the TSEs throughout the period of the terms of reference of the Inquiry. 23. The following is a chronology of papers submitted to the Veterinary Record, but which went unpublished: 5 1988: Letter entitled ‘Scrapie, Time to take HB Parry Seriously’ (YB88/6.8/4.1) http://www.bseinquiry.gov.uk/files/ws/s067.pdf Time to take HB Parry Seriously’ (YB88/6.8/4.1) If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notificable disease. ... http://www.bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf H. B. Parry, Scrapie Disease in Sheep--Historical, Clinical, Epidemiological, Pathological and Practical Aspects of the Natural Disease (Academic Press, London, 1983). http://www4.fao.org/cgi-bin/faobib.exe?database=faobib&rec_id=243466&search_type=ef_copy&de_worksheet=LOAN&de_copy_init=ECLOA&de_mail_pft=maill&lang=eng Title: SCRAPIE - TRANSMISSIBLE HEREDITARY DISEASE OF SHEEP ISSN: 0028-0836 Letters to the Editor Oncogenes in scrapie and Creutzfeldt-Jacob disease From Dr S J Oppenheimer Department of Tropical Paediatrics Liverpool School of Tropical Medicine http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1289692&blobtype=pdf From a historical viewpoint it should be noted that this point was first made strongly in relation to scrapie by Parry (1962, 1983), to whose work Oppenheimer rightly draws attention. R M RIDLEY H F BAKER T J CROW http://www.pubmedcentral.org/picrender.fcgi?artid=1290018&blobtype=pdf 1983 APPROVAL OF MATERIAL FOR PUBLICATIONS All material for publication including written works to be published in scientific journals, books, proceedings of scientific meetings, abstracts of verbally delivered papers and the like should be scrutinized for risk to the Ministry before dispatch to the publishers............. full text; http://www.bseinquiry.gov.uk/files/yb/1983/10/12001001.pdf 19. On 18th February, 1987 (YB87/2.18/1.1) I reported to Dr Watson and Dr Shreeve on a further case which we had received from Truro VIC. The brain had shown neuronal vacuolation and in brain extracts there were fibrils that were similar in size and appearance to SAFs from sheep with scrapie. The Virology Department was studying the brain further and considering a transmission study. A few weeks before this, I had discussed the possibility of a transmission study with Michael Dawson, a research officer in the Virology Department and an expert in viral diseases in sheep, and we were considering carefully the safety aspects. In my note I raised the question of whether we should disclose the information we had more widely to the VIS because this may assist in getting any other cases referred to CVL but there was the difficulty that we knew very little about the disorder and would be unable to deal with queries that might be raised. 20. On 23rd February, 1987 (YB87/2.23/1.1) I sent Mr Wells a note asking him to prepare a statement for publication in Vision, the in-house newsheet prepared by the VIS for the SVS, setting out details of what we had discovered. On 24th February, 1987 (YB87/2.25/2.1) Gerald Wells indicated in a note to me that he had discussed the proposed article with Mr Dawson and they both believed that it could be damaging to publish anything at that stage. They believed cases would be referred to CVL in any event because they were unusual and they did not feel "Vision" was an appropriate publication because its confidentiality was questionable and might lead to referrals to veterinary schools rather than CVL. Gerald Wells was also concerned about the resources available in his section to deal with referred cases. I replied (YB87/2.25/2.1) indicating a draft statement was needed by the Director before a decision on publication could be made. Gerald Wells prepared a draft statement (YB87/3.2/2.1) and sent it to me on 2nd March, 1987. In his cover note (YB87/3.2/1.1) he commented that he believed the distribution of any statement about the new disease outside of CVL to be premature because there was so little information available about the new disease. I passed on a copy of Gerald Wells' note to Dr Watson (YB87/3.2/3.1). I discussed the matter of publication with Dr Watson. No decision had been taken to publish any material at that stage and I sent a note to Gerald Wells letting him know the position and confirming that his views and those of Michael Dawson would be taken into account when a decision was taken. - 11 - 21. In March, 1987 serious consideration was given to possible transmission (e.g. to hamsters) and other experiments (other than the collection of epidemiological data by the VIS and clinicopathology which had been in progress since the first cases were recognised in November, 1986). 22. On 23rd April, 1987 I sent a report (YB87/4.23/1.1) to Dr Watson and Dr Shreeve informing them that nine control brains were being examined for SAFs and a cow which appeared to be affected with BSE had been purchased for observation. The cow had come from the farm where the original cases had developed and had arrived at CVL on 22nd April, 1987. 23. On 15th May, 1987 Dr Watson informed me that the proposed "Vision" draft would be circulated to VICs in England and Wales if it was approved by management. On 22nd May, 1987 I was copied in on a note (YB87/5.22/2.1) from B.M Williams, (who I believe was Head of the VIS at this time but retired shortly after this), to Dr Watson. This confirmed that the draft prepared for publication in Vision was approved but that the final paragraph should be amended to make it clear that knowledge of the new disease should not be communicated to other research institutes or university departments. At a meeting with Dr Watson on 2nd June, 1987 he informed me that no communication should be made with NPU until after the meeting with the CVO on 5th June, 1987 (see my note of 3rd June, 1987 – YB87/6.3/1.1). We needed much more data and information to answer inevitable queries. ... http://www.publications.parliament.uk/pa/cm199900/cmselect/cmsctech/465/465m48.htm An Anglo-German Comparison of Risk Political Cultures The BSE Case Kerstin Dressel sine-Institute Munich, Germany kerstin.dressel@sine-institut.de The following report include excerpts of a thesis submitted in fulfilment of the requirements for the degree of Doctor rerum politicarum (Dr. rer. pol.) at the Ludwig-Maximilians-University of Munich supervisor: Prof Dr Ulrich Beck Institute for Sociology, Munich, Germany The British case study was prepared at the Centre for the Study of Environmental Change at Lancaster University, UK, Supervisor: Prof Dr Brian Wynne kindly supported by a grant of the Economic and Social Research Council, UK Munich, 2nd October 2000 The BSE Inquiry / Statement No 67 http://www.bseinquiry.gov.uk/files/ws/s067.pdf USDA USA Gerald Wells: Report of the Visit to USA, April-May 1989 snip... The general opinion of those present was that BSE, as an snip... It is clear that USDA have little information and _no_ regulatory snip... 3. Prof. A. Robertson gave a brief account of BSE. The US approach snip... http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf Suppressed peer review of Harvard study October 31, 2002 http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf USDA BSE inconclusive MRR policy FDA, which is responsible for the safety of animal feed, immediately began an investigation. On Friday and throughout the weekend, FDA investigators inspected the slaughterhouse, the rendering facility, the farm where the animal came from, and the processor that initially received the cow from the slaughterhouse. FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA. ... BESIDES the Texas mad cow that sat on the shelf for 7+ months before the Honorable Phyllis Fong of the OIG finally did the end around Johanns et al and finally had Weybridge bring that negative cow back from the dead to finally being a confirmed mad cow (hint, hint, getting MRR implemented first), was this simply another bumbling of BSE protocol, or just same old same old; USDA Press Office (202) 720-4623 Statement by Chief Veterinary Medical Officer John Clifford Animal and Plant Health Inspection Service Regarding Non-Definitive BSE Test Results Our laboratory ran the IHC test on the sample and received non-definitive results that suggest the need for further testing. As we have previously experienced, it is possible for an IHC test to yield differing results depending on the “slice” of tissue that is tested. Therefore, scientists at our laboratory and at Weybridge will run the IHC test on additional “slices” of tissue from this animal to determine whether or not it was infected with BSE. We will announce results as soon as they are compiled, which we expect to occur by next week. I would note that the sample was taken in April, at which time the protocols allowed for a preservative to be used (protocols changed in June 2005). The sample was not submitted to us until last week, because the veterinarian set aside the sample after preserving it and simply forgot to send it in. On that point, I would like to emphasize that while that time lag is not optimal, it has no implications in terms of the risk to human health. The carcass of this animal was destroyed, therefore there is absolutely no risk to human or animal health from this animal. "The veterinarian treated the sample with a preservative which readies it for testing using the immunohistochemistry test, an internationally recognized confirmatory test for BSE. "Neither the rapid screening test nor the Western blot confirmatory test can be conducted on a sample that has been preserved. Our laboratory ran the IHC test on the sample and received non-definitive results that suggest the need for further testing. "As we have previously experienced, it is possible for an IHC test to yield differing results, depending on the slice of tissue that is tested. Therefore scientists at our laboratory and at Weybridge will run the IHC test on additional slices of tissue from this animal to determine whether or not it was infected with BSE. "We will announce results as soon as they are compiled, which we expect to occur by next week. NOW, all the above announced July 27, 2005. SO, the other 'inconclusive' sample has been sitting on the shelf since April, some 4 months earlier, give or take a few days. NOW, what has been going on while this other inconclusive BSE/BASE mad cow sits on the shelf. Lets look at that BSE MRR COMMODITY time frame ;-) KEEP THEM DOGGIES ROLLING, RAWHIDE, ye ha ! REPORT OF THE COMMITTEE ON SCRAPIE Chair: Dr. Jim Logan, Cheyenne, WY Vice Chair: Dr. Joe D. Ross, Sonora, TX Dr. Deborah L. Brennan, MS; Dr. Beth Carlson, ND; Dr. John R. Clifford, DC; Dr. Thomas F. Conner, OH; Dr. Walter E. Cook, WY; Dr. Wayne E. Cunningham, CO; Dr. Jerry W. Diemer, TX; Dr. Anita J. Edmondson, CA; Dr. Dee Ellis, TX; Dr. Lisa A. Ferguson, MD; Dr. Keith R. Forbes, NY; Dr. R. David Glauer, OH; Dr. James R. Grady, CO; Dr. William L. Hartmann, MN; Dr. Carolyn Inch, CAN; Dr. Susan J. Keller, ND; Dr. Allen M. Knowles, TN; Dr. Thomas F. Linfield, MT; Dr. Michael R. Marshall, UT; Dr. Cheryl A. Miller, In; Dr. Brian V. Noland, CO; Dr. Charles Palmer, CA; Dr. Kristine R. Petrini, MN; Mr. Stan Potratz, IA; Mr. Paul E. Rodgers, CO; Dr. Joan D. Rowe, CA; Dr. Pamela L. Smith, IA; Dr. Diane L. Sutton, MD; Dr. Lynn Anne Tesar, SD; Dr. Delwin D. Wilmot, NE; Dr. Nora E. Wineland, CO; Dr. Cindy B. Wolf, MN. The Committee met on November 9, 2005, from 8:00am until 11:55am, Hershey Lodge and Convention Center, Hershey, Pennsylvania. The meeting was called to order by Dr. Jim Logan, chair, with vice chairman Dr. Joe D. Ross attending. There were 74 people in attendance. The Scrapie Program Update was provided by Dr. Diane Sutton, National Scrapie Program Coordinator, United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS), Veterinary Services (VS). The complete text of the Status Report is included in these Proceedings. Dr. Patricia Meinhardt, USDA-APHIS-VS-National Veterinary Services Laboratory (NVSL) gave the Update on Genotyping Labs and Discrepancies in Results. NVSL conducts investigations into discrepancies on genotype testing results associated with the Scrapie Eradication Program. It is the policy of the Program to conduct a second genotype test at a second laboratory on certain individual animals. Occasionally, there are discrepancies in those results. The NVSL conducts follow-up on these situations through additional testing on additional samples from the field and archive samples from the testing laboratories. For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory’s certification was revoked by APHIS-VS. To reduce/eliminate these problems, the Program has placed additional quality requirements on the testing laboratories: additional review of final reports, additional coding systems for testing operations, strict follow-up and reports to NVSL on corrective actions, dual data entry systems, and more frequent inspections. ........ In November 2004, USDA announced that its rapid screening test produced an inconclusive BSE test result. A contract laboratory ran its rapid screening test on a brain sample collected for testing and produced three high positive reactive results. As required, the contract laboratory forwarded the inconclusive sample to APHIS’ National Veterinary Services Laboratories (NVSL) for confirmation. NVSL repeated the rapid screening test, which again produced three high positive reactive results. Following established protocol, NVSL ran its confirmatory test, an immunohistochemistry (IHC) test, which was interpreted as negative for BSE. Faced with conflicting results between the rapid screening and IHC tests, NVSL scientists recommended additional testing to resolve the discrepancy but APHIS headquarters officials concluded that no further testing was necessary since testing protocols were followed and the confirmatory test was negative. In our discussions with APHIS officials, they justified their decision to not do additional testing because the IHC test is internationally recognized as the "gold standard" of testing. Also, they believed that USDA/OIG-A/50601-10-KC/ Page iv conducting additional tests would undermine confidence in USDA’s testing protocols. OIG obtained evidence that indicated additional testing was prudent. We came to this conclusion because the rapid screening tests produced six high positive reactive results, the IHC tests conflicted, and various standard operating procedures were not followed. Also, our review of the relevant scientific literature, other countries’ protocols, and discussions with experts led us to conclude that additional confirmatory testing should be considered in the event of conflicting test results. To maintain objectivity and independence, we requested that USDA’s Agricultural Research Service (ARS) perform the Office International des Epizooties (OIE) Scrapie-Associated Fibrils (SAF) immunoblot test. The additional testing produced positive results. To confirm, the Secretary of Agriculture requested that an internationally recognized BSE laboratory in Weybridge, England (Weybridge) perform additional testing. Weybridge conducted various tests, including their own IHC tests and three Western blot tests. The tests confirmed that the cow was infected with BSE. The Secretary immediately directed USDA scientists to work with international experts to develop new protocols that include performing dual confirmatory tests in the event of an inconclusive BSE screening test. We attribute the failure to identify the BSE positive sample to rigid protocols, as well as the lack of adequate quality assurance controls over its testing program. Details of our concerns are discussed in Findings 3 and 4. immunoblot.45 ARS performed the test at the National Animal Disease Center because NVSL did not have the necessary equipment46 (ultracentrifuge) to do the test. APHIS scientists observed and participated, as appropriate, in this effort. The additional tests conducted by ARS produced positive results. To confirm this finding, the Secretary requested the internationally recognized BSE reference laboratory in Weybridge, England, (Weybridge) to perform additional confirmatory testing. Weybridge conducted various tests, including their own IHC methods, as well as three Western blot methods. The tests confirmed that the suspect cow was infected with BSE. Also, Weybridge confirmed this case as an unequivocal positive case of BSE on the basis of IHC. As a result of this finding, the Secretary immediately directed USDA scientists to work with international experts to develop a new protocol that includes performing dual confirmatory tests in the event of another inconclusive BSE screening test. Finding 3 Rigid Protocols Reduced the Likelihood BSE Could be Detected APHIS relied on a single test method, as well as a histological examination of tissue for lesions consistent with BSE, to confirm the presence of BSE even though discrepant test results indicated further testing may be prudent. When IHC test results were interpreted as negative, APHIS concluded the sample tested negative for BSE. Subsequent independent tests initiated by OIG using a different testing method, as well as confirmatory testing by Weybridge, determined that the suspect sample was a positive case of BSE. APHIS Declares BSE Sample Negative Despite Conflicting Results When the tissue sample originally arrived at NVSL in November 2004 from the contract lab, NVSL scientists repeated the ELISA screening test and again produced three high positive reactive results. NVSL scientists cut out two sections of the brain sample for IHC testing. One section was used for an experimental procedure that was not part of the confirmatory testing protocol, and the other cut was for normal IHC testing using scrapie for a positive control.47 According to NVSL scientists, the experimental test results were inconclusive but the IHC test was interpreted as negative. The NVSL scientists were concerned with the inconsistencies and conducted 45 The OIE SAF immunoblot is an internationally recognized confirmatory test, often referred to as a Western blot test. There are different types of Western blots; the OIE SAF immunoblot includes enrichment steps taken with the sample prior to the standard Western blot steps. 46 APHIS has now ordered the necessary equipment for NVSL. USDA/OIG-A/50601-10-KC Page 32 47 A positive control is a sample that is known to contain a given disease or react in the test. The sample then can be used to make sure that the test for that disease works properly. In the case of BSE, tissue infected with either scrapie or BSE can serve as a positive control for an IHC test for BSE since both are different forms of the same disease (transmissible spongiform encephalopathy or TSE). another IHC test using BSE as a positive control.48 The test result was also interpreted as negative. Also, according to the NVSL scientists, the histological examination of the tissue did not detect lesions consistent with BSE. After the second negative IHC test, NVSL scientists supported doing additional testing. They prepared a plan for additional tests; if those tests had been conducted, BSE may have been detected in the sample. The additional tests recommended by NVSL scientists, but not approved by APHIS Headquarters officials, were the IHC using other antibodies (IHC testing using different antibodies ultimately produced positive results); IHC testing of additional regions of the brain (the cerebellum tested positive); regular and enriched (OIE-like) Western blots (the obex and cerebellum tested positive); and variable rapid tests (the obex and cerebellum tested positive with two different rapid tests). NVSL officials also recommended that the sample be sent to Weybridge for confirmatory testing (to conduct IHC and OIE Western blot tests). In June 2005, Weybridge conducted IHC testing with three different antibodies, including the antibody used in the United States (tested positive), the OIE Western blot (tested positive), a modified commercial kit Western blot (negative) and the NaPTA49 Western blot (tested positive). We obtained information as to the differing protocols used by other countries. We found that while APHIS determined that additional testing was unnecessary after the IHC test, other countries have used multiple tests to confirm positives. In Japan, for example, all reactive screening test samples are examined by both IHC and a Western blot (different from the OIE SAF immunoblot). In the United Kingdom (U.K.), IHC and Western blot (different from the OIE SAF immunoblot) tests are used for all animals that test positive with a screening test. When IHC and the Western blot fail to confirm a positive rapid test, the U.K. resorts to a third test, the OIE SAF immunoblot. With these procedures in place, both Japan and the U.K. have found BSE cases that were rapid test reactive, IHC negative, and finally confirmed positive with a Western blot. Evidence Indicated Additional Testing Would Be Prudent We also spoke with an internationally recognized BSE expert regarding the advisability of limiting confirmatory testing when conflicting results are obtained. This official expressed concern about limiting confirmatory tests to the IHC despite its status as one of the “gold standard” tests. He advised that the IHC is not one test; it is a test method that can vary significantly in sensitivity from laboratory to laboratory. New antibodies can improve or USDA/OIG-A/50601-10-KC Page 33 48 The NVSL uses scrapie as the positive control as part of its normal IHC testing procedures. Due to the conflicting results between the ELISA and IHC tests, the NVSL conducted another IHC test with BSE as the positive control. Subsequently, the NVSL modified the Confirming Inconclusive Results from BSE Testing Laboratories at the NVSL SOP to show that all IHC tested BSE inconclusive samples from contract laboratories will use BSE as the positive control. 49 Sodium phosphotungstic acid. USDA/OIG-A/50601-10-KC Page 34 reduce sensitivity, as can variations in many of the reagents50 used. He explained that his laboratory had experienced cases where an initial confirmatory IHC test was challenged by either a more extensive IHC test or “…applying a more sensitive immunoblot.” He emphasized the importance of having additional confirmatory testing to resolve discrepant results since there are many variables, and most of the variability appears to be due to test performance of the laboratory. OIG became concerned that APHIS relied on its confirmatory test methods when rapid screening tests produced high positive reactive results six times.51 Also, we found that APHIS did not pursue and/or investigate why the ELISA produced high reactive positives. An official from the manufacturer of the ELISA test kit told us that they requested, but did not receive, information on the inconclusive reported by USDA in November 2004. These officials requested this information in order to understand the reasons for the discrepant results. The Bio-Rad ELISA rapid screening test is internationally recognized as a highly reliable test and is the rapid screening test used for USDA’s surveillance effort. According to APHIS officials, they felt it would be inappropriate to collaborate on the one sample because Bio-Rad is a USDA-APHIS regulated biologics company and only one of several competing manufacturers. To maintain confidence in USDA’s test protocols, it would have been a prudent course of action for USDA to determine why such significant differing results were obtained. The fact that they did not pursue this matter caused concerns relating to testing quality assurance procedures. In this regard, we found lack of compliance with SOPs relating to laboratory proficiency and quality assurance (see Finding 4), and, in this case, the storage of sampled material and reporting of test results. We found that the NVSL did not prepare a report to document its confirmatory testing of the November 2004 sample. The SOP52 states that the BSE network laboratory initiating the inconclusive will receive a report of the case. NVSL officials could not explain why a final report had not been prepared. We also found that the inconclusive sample was frozen prior to IHC confirmatory testing. APHIS protocols state that samples are not to be frozen prior to laboratory submission. The OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals states that the tissues for histological or IHC examination are not to be frozen as this will provide artefactual53 lesions that may compromise the identification of vacuolation,54 and/or target site location. Although the sample was frozen, APHIS did not conduct a Western 50 A substance used in a chemical reaction to detect, measure, examine, or produce other substances. 51 The six high positive reactive results were from three tests of the submitted sample (multiple runs of the same test). 52 Confirming Inconclusive Results from Bovine Spongiform Encephalopathy Testing Laboratories at the NVSL SOP, dated August 13, 2004. 53 A structure or feature not normally present but visible as a result of an external agent or action, such as one seen in a microscopic specimen after fixation. 54 A small space or cavity in a tissue. USDA/OIG-A/50601-10-KC Page 35 blot test on the sample. An NVSL official said freezing the sample does not make it unsuitable for IHC. APHIS determined that the sample was suitable for IHC and therefore, in accordance with its SOP, did not conduct a Western blot test. APHIS also handled the December 2003 BSE positive differently than the November 2004 sample. For the December 2003 BSE positive sample, APHIS conducted several confirmatory tests in addition to the IHC testing and histological examination (unlike the November 2004 sample tests, both of these were interpreted as positive). ARS performed two Western blots (Prionics Check Western blot and an ARS developed Western blot). When we questioned why the samples were handled differently, APHIS officials stated that the Western blots were done because the IHC in December 2003 was positive. The additional testing was done to further characterize the case, because it was the first U.S. case; the additional testing was not done to decide whether the case was positive or negative. We discussed our concerns with limiting confirmatory testing, particularly given conflicting results, with the APHIS Administrator and staff in May 2005. He explained that international standards recognized more than one “gold standard” test. In setting up its testing protocols, USDA had chosen one as the confirming test, the IHC test, and stayed with it. APHIS protocols only allow a Western blot in cases where the sample has become unsuitable for IHC tests (e.g., in cases where the brainstem architecture is not evident). International standards, he continued, accept a tissue sample as negative for BSE if its IHC test is negative. Once the test is run in accordance with protocols, additional tests undermine the USDA testing protocol and the surveillance program. He concluded that since APHIS’ protocols accepted the IHC test as confirming the presence or absence of BSE, no further testing was necessary. According to protocol, the tissue sample was determined to have tested negative for BSE. On June 24, 2005, USDA announced that the additional testing by the BSE reference laboratory in England confirmed the presence of BSE in the tissue sample. To obviate the possibility that a future sample would be declared negative and then found positive, the Secretary of Agriculture announced a change to APHIS’ testing protocols that same day. He called for “dual confirmatory tests in the event of another ‘inconclusive’ [reactive] BSE screening test.” He also indicated that he would reinforce proper procedures so that samples will not be frozen, and to spot-check the laboratories to see that they complete reports as required. APHIS issued a SOP on the new confirmatory testing protocols on November 30, 2005. WASHINGTON, June 24, 2005 -- Agriculture Secretary Mike Johanns today announced that the U.S. Department of Agriculture has received final test results from The Veterinary Laboratories Agency in Weybridge, England, confirming that a sample from an animal that was blocked from the food supply in November 2004 has tested positive for bovine spongiform encephalopathy (BSE). Johanns also directed USDA scientists to work with international experts to thoughtfully develop a new protocol that includes performing dual confirmatory tests in the event of another "inconclusive" BSE screening test. HOWEVER, when Dr. Detwiler tried to tell them this in 2003, they shot the messenger ; USDA 2003 We have to be careful that we don't get so set in the way we do things that Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't Dr. Keller: Tissues are routinely tested, based on which tissue provides an Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't ============================= International Scientific Advisory Council COUNCIL MEMBERS Dr. Neil Cashman. Diener Professor of Neurodegenerative Diseases and Director, Neuromuscular Disease Clinic, Sunnybrook & Women's Health Sciences Center, University of Toronto. Specialist in motor neuron diseases and the cell biology of amyloid encephalopathies, including prion illnesses. Author of over 250 publications. Recipient of the 2000 Jonas Salk Prize for biomedical research. Dr. Dean Danilson. Vice President QAFS, Tyson Foods, Inc. Responsible for quality assurance and food safety programs for the retail division for fresh beef, pork, poultry and ready-to-eat meats. Dr. Linda Detwiler. Adjunct Professor, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland. Also provides private animal health consulting services, with specializations in transmissible spongiform encephalopathies, emergency preparedness, and animal product issues related to imports and exports. Formerly Senior Staff Veterinarian, Emergency Programs Staff, U.S. Department of Agriculture Animal and Plant Health Inspection Service, the unit principally responsible for surveillance, prevention, and education activities related to BSE. Member of various international working groups and advisory committees on TSEs. Author of numerous articles on the issues. Alan A. Harris, M.D. Professor of Internal Medicine and Preventive Medicine, Senior Assistant Chairman, Department of Internal Medicine, Hospital Epidemiologist, Rush-Presbyterian-St. Luke's Medical Center. Specialist in public health and foodborne illnesses. Fellow, Infectious Diseases Society of America. Fellow, American College of Physicians. Member, Society of Healthcare Epidemiology of America. Author or co-author of more than 140 scientific publications. Dr. Beat Hörnlimann, MPH. Managing Director, SVISS Consulting, BSE 7192 Ltd., an organization that provides expert advice on public and animal health, particularly with respect to BSE. Formerly Chief Veterinary Officer, Public Health Department, Kanton Zug, Switzerland. Led Swiss BSE and scrapie eradication program and served in numerous other senior-level staff and advisory positions related to TSEs. Author of a book on prions and prion diseases in humans and animals. Dr. David Kessler. Dean, School of Medicine, Yale University and former Commissioner, U.S. Food and Drug Administration. Author of A Question of Intent (on federal tobacco regulation efforts) and numerous articles in major medical journals. Member, Board of Directors, Elizabeth Glaser Pediatric AIDS Foundation, Doctors of the World, National Center for Addiction and Substance, Henry Kaiser Family Foundation. Recipient of numerous medical public service awards, including the American Heart Association National Public Affairs Special Recognition Award, American Academy of Pediatrics Excellence in Public Service Award, and American Cancer Society Medal of Honor. Dr. Colin Masters. Professor and Head, Department of Pathology, University of Melbourne. Specialist in neuropathology. Member, numerous national and international medical professional societies. Dr. Carols Messuti. Ministry of Livestock, Agriculture, and Fishing, Government of Uruguay and Delegate to the OIE, the UN's principal agency for animal diseases. Dr. Jeffrey W. Savell. Professor, E.M. ?Manny? Rosenthal Chairholder, and Leader, Meat Science Section, Department of Animal Science, Texas A&M University. Specialist in meat quality/consistency, food safety and nutrition. Past President, American Meat Science Association; member, Institute of Food Technologists, American Society of Animal Science, HACCP Alliance. Author or co-author of more than 250 articles and co-author of the Laboratory Manual for Meat Science. Recipient of numerous awards for research and teaching. Dr. James Toole. Walter C. Teagle Professor of Neurology, Professor of Public Health Sciences, and Director, Stroke Research Center, Wake Forest University School of Medicine. President, International Stroke Society; member and past-president, World Federation of Neurology; member and past-president American Neurological Association; fellow, Royal College of Physicians; master, American College of Physicians. Author of Cerebrovascular Disorders and over 600 medical textbook chapters; co-editor Handbook of Clinical Neurology. Former editor, Journal of the Neurological Sciences. USDA, FSTS Docket Clerk 300 12* Street, SW Room 102, Cotton Annex Washington, DC 20250 04-021ANPR 04-021ANPR-70 Richard L. Crawford Re: Docket No: 04-02 1 ANPR Federal Measures to Mitigate BSE Risks: Considerations for Further Action Dear Sir or Madame: On behalf of McDonald’s Corporation, which operates more than 13,000 restaurants in the United States, we appreciate the opportunity to submit comments to this very important Advance Notice of Proposed Rulemaking (ANPRM). 69 Fed. Reg. 42288 (July 14,2004). In previous comments submitted to FSIS regarding the removal of SRI&, McDonalds fully supported this rule and its immediate implementation. The removal of SRMs from human food is the primary firewall to protect the US consumer from being exposed to the BSE agent. While we applaud the requirement for SRM removal, we feel that it is equally important for FSIS to insure that each slaughterplant which processes cattle have systems in place which prevent cross contamination between edible tissue and SRMs. This should include but not be limited to the use of separate equipment, such as knives, blades, etc. where appropriate. In addition, it is also important that appropriate and effective disinfection procedures for equipment used to handle SRMs be developed and approved for use. It is our opinion that requiring SRM removal without a procedure to prevent cross contamination is inadequate as a protective public health measure. The TSE agents @ions) are sticky and highly resistant to disinfection. If SRMs such as brain and spinal cord are allowed to contact equipment and other surfaces such as deboning tables which then are used to handle and process edible tissue this could allow contamination and negates the intention of the ban. This is true not only in plants slaughtering fed cattle both under and over 30 months but also in plants slaughtering predominately older cattle. It is important that measure be taken to prevent cross contamination between carcasses and SRms in the cull plants. McDonalds requires their suppliers to prevent cross contamination and audits against certain measurable standards such as requiring spinal cord to bc removed on the kill floor. We would be willing to share these standards with FSIS as an example. FSIS Docket No. 04-02 1 ANPR dooqhl- =w c1qo - McDonalds again recommends that dura (the covering around the brain and spinal cord) be added to the list of SRMs. While skull and vertebral column are included as SRMs, dura is not. If dura is not removed prior to processing on the fabrication floor, it may come loose and be incorporated into ground product. Bovine dura was never tested for infectivity. It was assumed that due to direct contact with spinal cord, it may serve as a vehicle to transmit disease. In addition, human dura has been the source of human to human transmission of Creutzfeldt-Jakob Disease (CJD). (personal communication - Dr. Danny Matthews, UK, VLA) Our ISAC committee recommended that McDonalds add the removal of dura as a specification in the production of our product. McDonalds urges the USDA to make the appropriate adjustments in the SRM ban if new scientific findings and/or the results of the increased surveillance warrant a change. In regards to imported meat products from other countries, McDonalds suggests that no SRM exemption be made for countries based on BSE risk. The long incubation period and limited surveillance in many countries can limit the ability to accurately determine risk. Also, the risk level of a country could potentially change over night if the trading patterns of a country changed. It seems logistically impossible to maintain a system which could continually monitor the world’s trading patterns. In addition, science has not provided all of the answers in regards to the transmission of BSE. Requiring SRMs to be removed from imported products for human food is prudent. If the US would wait until disease is confirmed the exposure would already have occurred. Thank you for the opportunity to comment on these very important issues. Richard L. Crawford Corporat,e Vice President, Government Relations McDonalds Corporation 1 Kroc Drive Oak Brook, Illinois 60523 FSIS Docket No. 04-021ANPR CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006 The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade. The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old. These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen. "The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that." Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive. USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general. "Everything they did on the Texas cow makes everything USDA did before 2005 suspect," Brown said. ...snip...end CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... CDC - Afterthoughts about Bovine Spongiform Encephalopathy and ... Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: As scientists and Irecognized experts who have worked in the field of TSEs for decades, we are deeply concerned by the recent discoveries of indigenous BSE infected cattle in North America and appreciate the opportunity to submit comments to this very important proposed rule We strongly supported the measures that USDA and FDA implemented to protect public health after the discovery of the case of bovine spongiform encephalopathy (BSE) found in Washington State in 2003. We know of no event or discovery since then that could justify relaxing the existing specified risk material (SRM) and non-ambulatory bans and surveillance that were implemented at that time. Further, we strongly supported the codification of those changes, as well as additional measures to strengthen the entire feed and food system. The discovery of additional cases of indigenous BSE in North America since that time has validated our position and strengthened OUT convictions. We caution against using the 18 month enhanced surveillance as a justification to relax or impede further actions. While this surveillance has not uncovered an epidemic, it does not clear the US cattle herd from infection. While it is highly likely that US and Canadian cattle were exposed to BSE prior to the 1997 feed ban, we do not know how many cattle were infected or how widely the infection was dispersed. BSE cases are most likely clustered in time and location, so while enhanced surveillance provides an 18 month snapshot, it does uot negate the fact that US and Canadian cattle were exposed to BSE. We also do not know in any quantitative or controlled way how effective the feed ban has been, especially at the farm level. At this point we cannot even make a thorough assessment of the USDA surveillance as details such as age, risk category and regional distribution have not been released. [GAO-05-101 ] Mad Cow Disease: FDA's Management of the Feed Ban Has Improved, but Oversight Weaknesses Continue to Limit Program Effectiveness [2] [GAO-05-101 ] Mad Cow Disease: FDA's Management of the Feed Ban Has Improved, but Oversight Weaknesses Continue to Limit Program Effectiveness http://frwebgate.access.gpo.gov/cgi-bin/useftp.cgi?IPaddress=162.140.64.88&filename=d05101.txt&directory=/diskb/wais/data/gao 03-025IFA Subject: Substances Prohibited from Use in Animal Food or Feed, Proposed Rule, Docket No. 2002N-0273 C-534 VOL 45 (PhRMA) and Entered On February 17, 2006 Marie A. Vodicka, PhD Assistant Vice President Biologics & Blotechnology Scientlflc & Regulatory Affairs SCIENCE & REG AFFAIRS Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, rrn . 1061 Rackville, MD 20862 No. 2002N-0273 February 14, 2006 Dear Sir or Madam : The Pharmaceutical Research and Manufacturers of America (PhRMA) is providing comment to the proposed rules issued. ...... Subject: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed PAUL BROWN December 20,2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed Dear Sir or Madame: As scientists and Irecognized experts who have worked in the field of TSEs for decades, we are deeply concerned by the recent discoveries of indigenous BSE infected cattle in North America and appreciate the opportunity to submit comments to this very......... oral route with just .OO1 gram of infected tissue, it may not take much infectivity to contaminate feed and keep the disease recycling. ........ http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf NOT TO SPEAK OF THE 11,000+ TONS OF MAD COW TAINTED FEED RECALL JUST ANNOUNCES ; EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) Report The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003. The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties. A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries. EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases. Terry S. Singeltary Sr.
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