Bovine spongiform encephalopathy
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Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is a fatal, neurodegenerative disease of cattle, which infects by a mechanism that shocked biologists on its discovery in late 20th century and appears transmissible to humans. While never having killed cattle on a scale comparable to other dreaded livestock diseases, such as foot and mouth and rinderpest, BSE has attracted wide attention because of its apparent transmissibility and lethality to humans, as well as for the nature of the mental decay it causes.
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Infectious agent
Unlike other kinds of infectious disease which are spread by microbes, the infectious agent in BSE is a specific type of protein. Misshaped ("misfolded") prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE). TSEs can arise in animals that carry a rare mutant prion allele, which expresses prions that contort by themselves into the disease-causing shape. Most TSEs, however, occur sporadically, in animals that do not have a prion protein mutation. Transmission can occur when healthy animals consume tainted tissues from others with the disease. In the brain these proteins cause native cellular prion protein to deform into the infectious state which then goes on to deform further prion protein in an exponential cascade. These aggregate to form dense plaque fibers, which lead to the microscopic appearance of "holes" in the brain, degeneration of physical and mental abilities and ultimately death.
The BSE epidemic in British cattle
The British BSE epidemic in cattle was recognised in 1986. It was first believed to have originated in sheep, in which the related prion disease scrapie is common (such diseases collectively are called "transmissible spongiform encephalopathies" or TSEs. However, sheep and cattle TSEs are quite different and it is now thought more likely that BSE could have originated with a case of sporadic BSE in a single bovine. Prior to the BSE epdemic, cattle were fed with meat and bone meal, a high-protein substance obtained from the remnants of butchered animals, including cows and sheep. This practice allowed the accumulation of prions over many generations. As more animals became ill, more infectious tissue got into the feed, and so the number of cases reached epidemic proportions. The tissues that contain most of the pathogenic molecules are those of the brain and the nervous system, although infectious amounts have been shown experimentally to be present elsewhere, such as blood.
The use of meat and bone meal as a protein supplement in cattle feed was widespread in Europe prior to about 1987. Soybean meal is the primary plant-based protein supplement fed to cattle. However, soybeans do not grow well in Europe, so cattle raisers throughout Europe turned to the less expensive animal byproduct feeds as an alternative. A change to the rendering process in the early 1980's may have resulted in a large increase of the infectious agents in the cattle feed. A contributing factor seems to have been lax British laws that did not require a high temperature sterilization of the protein meal. While other European countries like Germany required the said animal byproducts to undergo a high temperature steam boiling process, this requirement had been eased in Britain as a measure to keep prices competitive.
Following an epidemic of BSE in Britain, 157 people (as of 2004) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. This is a separate disease from 'classical' Creutzfeldt-Jakob disease, which is not related to BSE and has been known about since the early 1900s. Of the 157 cases of vCJD in humans so far, 148 occurred in the United Kingdom, 6 in France, and one in Italy. Three cases of vCJD occurred in people who had lived in or visited Britain--one each in Ireland, Canada and the United States. There is also some concern about those who work with (and therefore inhale) cattle meat and bone meal, such as horticulturists, who use it as fertilizer. Up to date statistics on all types of CJD are published by the UK CJD Surveillance Centre (http://www.cjd.ed.ac.uk) in Edinburgh. For many of the vCJD patients, direct evidence exists that they had consumed tainted beef, and this is assumed to be the mechanism by which all affected individuals contracted it. Disease incidence also appears to correlate with slaughtering practices that led to the mixture of nervous system tissue with hamburger and other beef. It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epidemic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year (though the number of new cases currently seems to be dropping). This is attributed to the long incubation period for prion diseases, which are typically measured in years or decades. As a result the full extent of the human vCJD outbreak is still not fully known.
In 2004 researchers reported evidence of a second contorted shape of prions in a rare minority of diseased cattle. In other words, this implies a second strain of BSE prion. Very little is known about the shape of disease-causing prions, because their insolubility and tendency to clump thwarts application of the detailed measurement techniques of structural biology. But cruder measures yield a "biochemical signature" by which the newly discovered cattle strain appears different from the familiar one, but similar to the clumped prions in humans with traditional CJD (Creutzfeldt-Jakob Disease).The finding of a second strain of BSE prion raises the possibility that transmission of BSE to humans has been underestimated, because some of the individuals diagnosed with spontaneous or "sporadic" CJD may have actually contracted the disease from tainted beef. So far nothing is known about the relative transmissibility of the two disease strains of BSE prion.
UK epidemic and UK licensed medicines
During the course of the investigation into the BSE epidemic, an enquiry was also made into the activities of the Department of Health and its Medicines Control Agency. On May 7, 1999 in his written statement number 476 (http://www.bseinquiry.gov.uk/files/ws/s476.pdf#search='David%20Osborne%20Hagger') to the BSE Inquiry, David Osborne Hagger reported on behalf of the Medicines Control Agency that in a previous enquiry the Agency had been asked to:
"... identify relevant manufacturers and obtain information about the bovine material contained in children�s vaccines, the stocks of these vaccines and how long it would take to switch to other products." It was further reported that the: "... use of bovine insulin in a small group of mainly elderly patients was noted and it was recognised that alternative products for this group were not considered satisfactory." A medicines licensing committee report that same year recommended that: "... no licensing action is required at present in regard to products produced from bovine material or using prepared bovine brain in nutrient media and sourced from outside the United Kingdom, the Channel Isles and the Republic of Ireland provided that the country of origin is known to be free of BSE, has competent veterinary advisers and is known to practise good animal husbandry." In 1990 the British Diabetic Association became concerned regarding the safety of bovine insulin and the government licensing agency assured them that: "... there was no insulin sourced from cattle in the UK or Ireland and that the situation in other countries was being monitored." In 1991 a European Community Commission: "... expressed concerns about the possible transmission of the BSE/scrapie agent to man through use of certain cosmetic treatments." Sources in France reported to the British Medicines Control Agency: "... that there were some licensed surgical sutures derived from French bovine material." Concerns were also raised: "... regarding a possible risk of transmission of the BSE agent in gelatin products."
BSE in North America
As of January 2005, five BSE-infected cattle have been identified in North America. The first was in 1993, involving an animal born in Britain. The second was reported in Canada on May 20, 2003. It occurred in a single older cow that may have contracted the disease from contaminated feed in earlier years. The animal had been destroyed and declared unfit for consumption prior to being diagnosed. The United States issued a temporary ban on all Canadian beef.
On December 23, 2003, the first case of BSE in the United States was found in a single Holstein cow in Washington State. Agriculture Secretary Ann Veneman called the discovery "a clear indication that our surveillance and detection program is working." However, the United States tested only 20,526 cows in 2003 out of the roughly 35 million slaughtered. Current tests reveal the presence of misshaped prions when they are abundant, but it is not known how far the disease must progress in an individual to transmit it to others. Therefore, it is possible that even among those cattle that are tested and classified as negative, a proportion nevertheless may be contagious. As a result, U.S. authorities have very little idea of how many American beef cattle might have the disease.
The government plans to double the number of cattle tested in 2004, and has banned the use of "downer cows" for human consumption. While the Washington cow that tested positive for BSE was reportedly unable to stand, veterinarians say the condition was unrelated to BSE. Furthermore, there is some dispute as to whether the cow was a downer or not.[1] (http://slate.msn.com/id/2097229/) Therefore it is not clear by how much the ban is liable to reduce the number of infected cattle consumed. Only 200,000 cows slaughtered in 2003 were downers.
The meat of the BSE-positive cow went to market, but some of it was successfully recalled before it was sold to consumers. U.S. authorities called for a switch to the testing procedure that is used in the United Kingdom, which yields its results in one day. Until the switch, U.S. surveillance relied on a test that gave results only after two weeks, after which time the meat from an animal usually has all been sold.
Shortly after the U.S. discovery of BSE, Japan and South Korea instituted a temporary ban on the import of U.S. beef, until more information about the US BSE outbreak becomes available. Since Japan and South Korea are the first- and third-largest importers of US beef, respectively, the economic impact of their bans is significant both for American cattle ranchers and for Japanese and Korean beef consumers. [2] (http://www.cnn.com/2003/BUSINESS/12/23/japan.madcow.reax/)
No case of variant Creutzfeldt-Jakob disease has occurred in North America so far, except among those who have travelled to Europe.
On June 10, 2005, the USDA reported a possible second case of BSE in the United States. Tests carried out at the USDA laboratory in Ames, Iowa indicate the presence of BSE, but confirmation from the Weybridge Veterinary Laboratory in the United Kingdom is still pending.
Husbandry practices in the United States relating to BSE
Soybean meal is cheap and plentiful in the United States. As a result, the use of animal byproduct feeds was never common, as it was in Europe. However, U.S. regulations only partially prohibit the use of animal byproducts in feed. In 1997, Regulations prohibited the feeding of mammalian byproducts to ruminants such as cows and goats. However, the byproducts of ruminants can still be legally fed to pets or other livestock and poultry such as pigs and chickens. In addition, it is legal for ruminants to be fed byproducts from some of these animals. [3] (http://www.prwatch.org/books/madcow.html)
In February 2001, the USGAO reported that the FDA, which is responsible for regulating feed, had not adequately policed the various bans. [4] (http://www.organicconsumers.org/madcow/cnn22602.cfm) Compliance with the regulations was shown to be extremely poor before the discovery of the Washington cow, but industry representatives report that compliance is now 100%. Even so, critics call the partial prohibitions insufficient. Indeed, US meat producer Creekstone Farms alleges that the USDA is preventing BSE testing from being conducted [5] (http://www.creekstonefarmspremiumbeef.com/csf_response.html).
BSE statistics by country
The following table summarizes reported cases of BSE and of vCJD by country. BSE is the disease in cattle, whilst vCJD is the disease in people.
| Country | BSE cases | vCJD cases |
|---|---|---|
| Austria | 2 | 0 |
| Belgium | 125 | 0 |
| Canada | 4 | 1 |
| Czech Rep | 9 | 0 |
| Denmark | 13 | 0 |
| Falkland Is | 1 | 0 |
| Finland | 1 | 0 |
| France | 891 | 6 |
| Germany | 312 | 0 |
| Greece | 1 | 0 |
| Hong Kong | 0 | 1 |
| Ireland | 1353 | 1 |
| Israel | 1 | 0 |
| Italy | 117 | 1 |
| Japan | 20 | 1 |
| Lichtenstein | 2 | 0 |
| Luxembourg | 2 | 0 |
| Netherlands | 75 | 1 |
| Oman | 2 | 0 |
| Poland | 14 | 0 |
| Portugal | 875 | 1 |
| Slovakia | 15 | 0 |
| Slovenia | 4 | 0 |
| Spain | 412 | 0 |
| Switzerland | 453 | 0 |
| UK | 183803 | 148 |
| US | 2 | 0 |
| Total | 188507 | 158 (+ 6 results pending) |
The figures given above for BSE are certainly too low, and most likely by a considerable amount. The tests used for detecting BSE vary considerably as do the regulations in various jurisdictions for when, and which cattle, must be tested. For instance, in the EU the cattle tested are older (30 months+), while many cattle are slaughtered earlier than that. At the opposite end of the scale, Japan tests all cattle at the time of slaughter. Tests are also difficult as the altered prion protein has very small levels in blood or urine, and no other signal has been found. Newer tests are faster, more sensitive, and cheaper, so it is possible that future figures may be more comprehensive. Even so, currently the only reliable test is examination of tissues during an autopsy.
It is noticeable that there are no cases reported in Australia and New Zealand where cattle are mainly fed outside on grass pasture and, mainly in Australia, non-grass feeding is done only as a final finishing process before the animals are processed for meat.
As for vCJD in humans, autopsy tests are not always done and so those figures too are likely to be too low, but probably by a lesser fraction. In the UK anyone with possible vCJD symptoms must be reported to the UK Creutzfeldt-Jakob Disease Surveillance Unit and so it is unlikely that any cases would be missed. In the U.S., the CDC has refused to impose a national requirement that physicians and hospitals report cases of the disease. Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University in Cleveland, which is funded by the CDC.