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Mad Cows Revisited
Mad Cows Revisited
Tony Tufariello, Stamford
Introduction
"Mad Cow Disease" discussed the state of basic knowledge about bovine spongiform encephalopathy (BSE), commonly known as “mad cow disease,” and the fears that it might be transmissible to humans through the consumption of beef, in a form called “variant Creutzfeld-Jakob disease” (v-CJD). Through 1995, such disease transmission to humans was still considered highly speculative by many scientists. Those beliefs were shattered when a spate of v-CJD cases involving very young persons occurred.
This bulletin will update the previous publication and present information now available on the causal factors, control methods, and potential liabilities. Readers wishing to review the available knowledge about BSE of just a year ago will want to obtain copies of Bulletin 109 on this topic.
In the short period of a year, several key developments have shaken the European Union (EU) and the United Kingdom in particular:
- Some 15 to 17 relatively young persons, between the ages of 15 and 46, have developed a new type of CJD (v-CJD), linked to the eating of BSE-infected beef or beef by-products, and most have since died of the illness.
- To control a near panic in beef markets, the EU banned the export of beef products and cattle from the UK.
- The UK was forced by public pressure and its EU partners into accepting a cull of 1.2 million cattle over 30 months of age - with the animals sacrificed and then incinerated.
- Some evidence for the “vertical transmission” of BSE from cow to calf was established and said to account for 1% of all cases.
- A test for BSE-linked proteins in spinal fluid was developed for use on humans and suspect cattle, to “rule out” other neurological causes.
- Experimenters using gel electrophoresis techniques, similar “DNA fingerprinting,” were able to show that prion proteins from v-CJD victims much more closely resembled BSE patterns than typical CJD ones – hinting strongly at transmission of the disease to humans from the eating of beef.
History
The peculiar effects of BSE on cows in Britain were first observed on dairy farms in 1981, although some estimate that only 100 cattle manifested the disease prior to 1987. Diseases with related effects in other species, most notably sheep, were called “scrapie” and have been known for hundreds of years. Since at least the time of World War I, sheep offal from slaughterhouses was rendered into high protein feed additives and fed to sheep and bovine cattle - largely dairy cows. Some current thinking is that changes in rendering processes in the late 1970s allowed the scrapie protein to better survive processing and end up in cattle feed, where it crossed the “species barrier” and caused BSE.
At the peak of the epidemic in cattle, BSE was being discovered in about 1,000 cattle a week in the UK. By late 1996, that rate had fallen to below 300 cases a week - ascribed to the effect of the “offal ban” - which in 1988 ended the feeding of processed slaughterhouse wastes to cattle in the UK. However, some EU members continued to import and use such offal-supplemented feed from UK sources until 1994 and “cheating” on the ban was said to be common in the UK.
In 1989, Britain banned the human consumption of “specified offals” (brain, spleen, thymus, tonsils, and gut), but many Britons had consumed such products in their luncheon meats, frankfurters, and meat pies prior to that time. Some cheating on this ban by farmers and abattoirs has also been reported - continuing to expose consumers to potentially contaminated beef products. In 1989, several valuable animals in the London Zoo contracted spongiform encephalopathies linked to BSE, possibly from eating infected beef.
In 1991, a calf born to a cow manifesting BSE also developed the disease, an indication of possible vertical transmission of the disease which was confirmed after similar cases occurred.
Why Britain?
The vast majority of BSE cases in cattle have occurred in Britain. There is no certain explanation for the severity of the epidemic there, but several peculiarities of the beef and dairy industries in Britain have been noted:
- Few other countries have used as much rendered offal in their cattle feed. In Britain, as much as 5% of feed was derived from offal.
- In the late 1970s, many renderers in Britain and on the Continent switched to continuous rendering processes of U.S. derivation. However, British renderers were said to use lower processing temperatures than did their Continental counterparts, explaining the greater carry-over of infective prions. Some discount this theory, pointing out that temperatures much higher than those used in rendering do not destroy the infectivity of prions. In fact, EU rendering rules, adopted in 1994, are said to not affect the prion proteins, which forced the EU to propose higher temperature “pressure cooking” methods for rendering, to be adopted by December 1, 1996.
- In Britain, there are far larger populations of sheep than there are of bovines, causing a higher percentage of all cattle offal to be scrapie-contaminated. In addition, UK shepherds are said to be more tolerant of scrapie-infected flocks than those on the continent or in the U.S..
- Whatever the reasons, the ban on specified offals in feed seems to have curbed the epidemic in cattle, although the earlier numbers provided for recognized BSE cases probably represent some under-reporting (larger numbers rounded):
Year Number of Confirmed BSE
Cases in Cattle (UK)
1986 17
1987 486
1988 3,000
1989 7,000
1990 15,000
1991 26,000
1992 37,000
1993 34,000
1994 23,000
1995 14,000
1996 8,000
1997 4,300
1998 3,200
1999 2,300
2000 1,300
Besides the unfortunate experience in the UK, illustrated above, BSE cases have also been reported in 10 other countries, including France, Portugal, Ireland, Switzerland, Belgium, Denmark, Germany, and Spain, where cattle illness has been linked to the use of contaminated British feed. In some other countries - the Falkland Islands, Oman, and Canada, - the cases were traced to live cattle imported from UK sources.
What About the U.S.?
Many have wondered aloud about the safety of U.S. beef and why no public reporting of BSE cases has occurred. In fact, although the FDA first proposed a ban on the use of sheep offals in bovine feeds in 1994, an industry outcry stayed regulatory action. After the evidence of economic harm to the UK beef industry in 1996, the U.S. livestock industry announced a “voluntary” ban on the use of ruminant offals in feed, as of March 1996. The FDA now plans to issue an offals ban in 1997, which will limit feed use of these materials to hogs, poultry, or pets. The U.S. livestock industry, with Department of Agriculture agreement, continues to insist that no cases of BSE have been observed in the U.S..
As noted earlier, the rendering processes for offal in the U.S. are similar to those used previously in Britain, with the possible exception of chosen temperatures, which tend to be higher stateside (typically 250oF vs. 212oF in the UK). In addition, offal constitutes a far smaller percentage of cattle feed in the U.S., with a much greater use of plentiful soybeans for protein supplementation in feeds. British calves are said to have received offal-supplemented feeds at a very early age while U.S. ranchers and dairymen historically utilize such feed later in the cow’s or steer’s life.
In the U.S., there are 100 million bovine cattle and 10 million sheep, while Britain typically has 40 million sheep and 11 million cattle - leading to the greater availability of much scrapie-infected offal as a cattle feed supplement in Britain. Before the 1988 ban in the UK, the offal from both sheep and bovines were rendered and added to cattle feed, so BSE in cows was fed back into the sheep and dairy and beef cattle herds.
As part of continuing U.S. Department of Agriculture (USDA) monitoring for BSE, 2,660 cattle brains from suspect cattle were examined from 1990 through 1996, with no signs of BSE found. Of the 499 cattle imported into the U.S. from Britain pre-1989, only 116 are still alive and being monitored.
The U.S. Food and Drug Administration (FDA) remains concerned about the safety of the three dozen or so drugs made from cattle tissue, with hundreds of other drug products containing bovine blood components. Cases of CJD have been transmitted through transplants of human tissue, including the cornea and dura mater (brain membrane), but none have been associated with transfusions of blood donated from CJD sufferers. Despite that history, the FDA has issued a prohibition on the use of bovine materials for pharmaceutical products from countries manifesting BSE in their herds.
To help provide for early identification of any U.S. occurrence of v-CJD cases, four states (California, Connecticut, Minnesota, and Oregon) have agreed to centralized reporting of any suspect CJD cases in humans.
Theory of Causation
There are a number of long-latency diseases of the brain which cause characteristic neurological problems and result in a brain with a “spongy” appearance. These include kuru (“the laughing death”), Creutzfeld-Jakob disease (CJD), fatal familial insomnia, and Gerstmann-Straussler-Scheinker (GSSD) disease. Most are extremely rare, with CJD “naturally” occurring in only 1 person per million population, kuru having stricken 2,600 South Pacific islanders since 1957, GSSD being found in only 50 extended families, and fatal familial insomnia identified in only 9 extended families - the last two suggesting strong genetic links. Until the early 1980s, there were few clues to the causes of these diseases, but a noted professor of neurology, Dr. Stanley Prusiner, developed a theory involving a new disease-causing entity: an infectious protein he named a prion. This theory has since gained much support, although some specialists continue to believe that either unidentified viruses, microorganisms known as spiroplasma, or even pesticides may be at fault. Unfortunately, no one has been able to identify a microorganism nor isolate any genetic material from diseased brain tissue that would allow replication in the body.
Unlike typical CJD, which rarely strikes those under 60 years of age (said to occur among those under 45 at an incidence of 5 cases per billion population), variant CJD has now stricken 15 persons under 45 in just the UK and France, with some victims as young as 15 years. Some characteristics of the two CJD diseases, both suspected of having prion causation, are provided later:
Typical CJD Variant CJD
Typical Age 55 to 70 yrs. 19 to 39 yrs.
At Onset
Features Dementia, Behavioural
myoclonus changes, ataxia,
numbness
Clinical Course Rapidly Insidious onset,
progressive more prolonged
course
Prion Deposits Synaptic deposits, Prominent florid
rarely plaques plaques
Prion Banding Type 1 & 2 Type 4 (similar
Pattern to BSE)
Oddly, the infectious prion suspected of causing these diseases is similar in chemical composition to the “normal” protein found throughout the brain - differing only in its structure - but able to “fold” the normal prion proteins into the dysfunctional variant and somehow damaging form. Prions have become the principal suspects for several reasons, not least of which is the observation that the infective agent is not destroyed by ultraviolet light, ionizing radiation, proteolytic (protein splitting) enzymes, or moderately high temperatures - although most of these agents destroy viruses, bacteria, or fungi, all of which contain nucleic acids. By contrast, prions contain no nucleic acids.
The initial assurances of beef safety by the British government, continuing until March 1996, were based largely upon the “species barrier” between humans and bovines. Sheep and bovines produce cellular prions differing from each other at only 7 positions, while human prions differ from those of bovines at 30 molecular locations. However, some researchers point out that protein conformance at several key points may be more important than overall structural conformance of the molecules.
Typical CJD has been experimentally transmitted by blood - a concern to blood banks - although cases in humans linked to blood transfusions are unknown. Earlier forms of human growth hormone, derived from the pituitary glands of cadavers, have transmitted CJD to youngsters. The typical form of CJD usually progresses to death within 6 months time, while the variant form may continue for 2 or more years until death. Both forms are invariably fatal, with the first symptoms developing after latency periods of an estimated 10 years. BSE in cattle is estimated to require a 5 to 6 year incubation period to manifest.
The knowledge base on this subject has advanced so rapidly, that a recent article in the journal Nature by Collinge (Vol. 383, October 24, 1996, p. 685 - 690) nearly positively linked BSE in cattle to variant CJD in humans, contracted through the eating of infected beef. To do this, the experimenters tested “prions” (protease-resistant infectious proteins) from different animal species suffering similar ailments and found that the gel electrophoresis patterns (a type of fingerprint) of proteins from BSE-infected cows were nearly identical to those from v-CJD infected humans but not to samples taken from conventional CJD sufferers. Even mice and monkeys infected with the cow disease developed prion patterns similar to those seen in the cow.
The Ban
Since our first bulletin on this topic in October 1995, the initial attempts by Germany to ban the import of British beef have developed into an EU-wide ban on beef products of all types from the UK. In March 1996, the British government admitted the possibility that victims of variant CJD may have contracted it from beef consumption - triggering a nearly immediate EU response - promulgation of a total ban on UK beef. In 1988, a ban on the use of specified offals in cattle feed had been enacted in the UK, although the EU only adopted the animal feed ban in 1994 and still allows pig and poultry feed outside the UK to be supplemented with offals.
Human consumption of the brain, spleen, spinal cord, and other nervous system tissues were banned in Britain in 1989, but new research indicates that such a ban may be inadequate. In a 1996 article in the The Lancet, researchers at Texas A&M reported that impact devices used to stun cattle at slaughter tend to propel quantities of brain tissue into the lungs. Interestingly, the lungs are still permitted in UK products like sausages. Furthermore, the investigators stated that it is likely that brain tissue would be found in other organs after use of pneumatic stunning devices - meaning that BSE infected cows which slip through screening processes may still be putting infectious prions into processed meat products being consumed today.
In recent months, it has been reported that random tests of cows being slaughtered showed laboratory evidence of BSE infection, although the animals may not have yet manifested neurological symptoms. In addition, before the total EU ban on British beef products, there were reports of false certifications by farmers that the beef came from herds free of the disease. Britain’s EU partners believe that these events have reinforced the continued need for a total ban on UK beef, which continues at the time of writing.
The Cull
Once the possibility of transmission to humans from the eating of beef was admitted by the UK, an emergency meeting of the EU in Florence reached agreement on the necessity to cull or destroy some 1.1 million British cattle over 30 months of age - based upon their likely exposure to scrapie-laced feed. Most of these cattle would be in dairy herds, sacrificed for meat once their milk-producing years were over. Most beef cattle are sacrificed at 2 years of age or less and never manifest the symptoms of BSE, although some wonder if their muscle tissue might nonetheless be infective to humans. Within the last month or so, an additional 100,000 UK cattle were added to the cull backlog - being those animals reared with animals that died of BSE and which may have eaten similar feed, as well as the offspring of cows that died of the illness.
The total cull stands at around 1.2 million head of cattle as of late December 1996, with $145 million allocated to the costs of destruction and farmer’s compensation for just the last 100,000 cattle. By late November 1996, about 1,000,000 head of cattle had already been destroyed in the UK.
The country with the second-highest incidence of BSE, Switzerland, has reported 223 cases versus 163,000 in Britain. Switzerland nonetheless planned to destroy one-eighth of its total herd in the Fall of 1996, comprising 230,000 cattle. In common with the UK, Swiss beef has been banned by many countries in Europe and elsewhere due to its BSE problems.
A complicating factor in all of these culls based upon the ages of the animals is that in an estimated 1% of cases, the disease is suspected of having been transmitted from the cow to calf, so a pool of “unculled” cattle may remain behind to pose a safety threat to the meat supply in the future. Although one might question the safety of milk produced from cows afflicted with BSE, there is no evidence that milk contains the prions or has caused v-CJD in humans.
Tests
Until recently, only microscopic examinations of brain tissue, obtained from sacrificed cows, sheep, or deceased humans, could positively confirm BSE, scrapie, or v-CJD, respectively. However, in the Fall of 1996, a group of researchers announced development of a test for a specific protein in cerebrospinal fluid which can accurately identify any of the transmissible spongiform encephalopathies, like CJD, v-CJD, BSE, and scrapie. The test requires a spinal tap to obtain the test fluid, so practical application to herds of cattle is probably remote. The test is only successful at detecting the proteins during manifestation of the disease - to help rule out other causes - not during the considerable incubation periods of 5 - 6 years in cattle and an estimated 10 years in humans.
Blood tests for evidence of CJD or v-CJD in humans have not been possible because the afflicted person develops no antibodies to the rogue prions and such antibodies are the markers for most other infections. However, British researchers do have a blood test for sheep to detect genetic susceptibility to scrapie, possibly allowing culling of those herds to eliminate the disease. One major worry is that BSE may transfer back to sheep from cattle offal added to their feed in years past, producing a mutant scrapie which is infective to humans. This concern has caused worry among lamb growers as well, although no v-CJD in humans has as yet been linked to the consumption of lamb.
Potential Liabilities
Firms dealing with beef and beef by-products may be exposed to litigation if their controls were inadequate. As late as 1994, some abattoirs were attempting to export beef from BSE-infected herds to the EU, contrary to government policy. Obvious liabilities would exist in such cases, although they would be complicated by the considerable latency of v-CJD and complicated traceability. Even with the recent bans on offal in feed and human foods, researchers have noted the potential for infected brain tissue to enter organs or muscle meat being consumed as food by animals and humans and some have estimated that roughly 1.8 million BSE-infected cattle will have been consumed by the year 2001.
One critical question - how many human consumers of beef will develop v-CJD in the future from having eaten contaminated products - cannot yet be answered. One scientist estimated that 500,000 Britons a year might be involved while others believe that 500 or less a year will develop the illness during the peak years to come, expected around 2003 (given the latency period).
Many food and pharmaceutical companies are interested in this disease because common products like milk and gelatin are derived from cows - although neither of those products are associated with BSE. Other common products containing beef by-products include candies, biscuits, bouillon cubes, pork sausages, gelatin desserts and pill coatings, cakes, mincemeat, chewing gums, and lipsticks. However, many of the beef by-products in these items are so processed that BSE transmission is considered highly unlikely. Nonetheless, some industry associations like the European Cosmetic, Toiletry, and Perfumery Association have advised members to avoid the use of gelatin from the UK - although the notice is advisory and ignorance of it is likely - establishing a negligence causation if later illness develops.
In Canada, the Red Cross has requested a recall of whole blood or blood products derived from donors known to suffer from typical CJD. Included are albumin, immune globulin, and coagulation factor VIII products. Obviously, such directives may establish standards for due diligence elsewhere, since these actions are known by the medical community and could be equally applicable to persons suffering from v-CJD.
Some British attorneys note that persons who contract v-CJD in Britain could sue beef retailers for “selling goods of an unsatisfactory quality” (Sale and Supply of Goods Act of 1994) and/or the beef processor for producing “defective goods.” The latter determination would depend upon whether or not the processor has changed the characteristics of the beef. Of course, it can be argued that use of a stunning device by the abattoir, found to distribute brain tissue to other edible organs and possibly even muscle tissue, is a processing-induced change. In any one of these potential legal actions, identification of the source for a beef-related illness would be difficult, considering the long latency period.
One legal discussion also considered potential employer’s liability actions by dairy farm or slaughterhouse employees - to name just two BSE-exposed occupations. Several cases of v-CJD have indeed occurred in dairy farmers, although slaughterhouse workers, butchers, or veterinarians have not suffered such illnesses since 1990. In addition, legal actions of this type by employees would have to establish the employer’s awareness of v-CJD risks and their disregard of them.
A separate concern in Britain involves the safe disposal of the 1.3 million cattle carcasses culled from herds because of age-linked exposure to contaminated feed. Early in the crisis, some farms dumped BSE-infected carcasses into landfills, which are leaching contaminated water into drinking water supplies. Most recent cattle destruction has utilized incineration, avoiding that particular problem.
In one legal study, the authors concluded that the BSE crisis did not appear to pose a high potential for many insurable losses. That assessment was written before the recent link between v-CJD in humans and BSE in cows, established experimentally, which may upset that sense of comfort.
Conclusion
It seems fair to conjecture that even today, some beef products being consumed in the UK and other EU countries are BSE contaminated and that additional v-CJD cases in humans will occur over the next 10 years or longer. One may speculate that there is a genetic predisposition to the ailment in some animals and humans, since far more cows than the reported 163,000 had been exposed to contaminated feed. If this is true, then the number of eventual human sufferers may be far fewer than even the most conservative present estimates.
For those persons who do develop v-CJD, causation may now be a less formidable hurdle to successful litigation, although
traceability to beef suppliers or feed manufacturers seems a real obstacle, unless something as revolutionary as “market share liability” (uncommon even in the U.S.) is adopted in possible class-action suits. Given the suspicions that some vertical transmission of BSE may occur between cow and calf, some wonder if humans suffering from v-CJD, which strikes during the reproductive years, might pass the disease to children, providing even slower claims development.
Despite the incomplete knowledge about these diseases, one should expect blood banks and organ transplantation centres to include inquiries about neurological symptoms as part of all donor screening - until effective tests for infectious prions in tissues or blood are developed. The FDA has recommended to blood collection centres that they screen out donors who received human pituitary growth hormone, have a family history of CJD, or received dura mater grafts. The FDA does not recommend exclusion of blood donors who received corneal transplants, because only one case of CJD, in 1971, has ever been linked to such tissues.
Despite such screening procedures, blood donations by CJD victims are still likely, given the long latency period. In November 1994, a frequent blood donor was diagnosed with CJD and blood centres conducted a recall of the resulting blood products. In March 1995, the FDA was again notified of a blood donor who developed CJD, triggering a recall of whole blood and blood fractions. On the positive side, no cases of CJD transmission have been linked to whole blood, plasma, or blood products and transmission of the disease to primates has not been demonstrated through infected blood, suggesting that the FDA actions have been largely precautionary. In Europe, the situation may be more difficult, because persons infected with diseased prions from beef may be blood donors before their v-CJD manifests symptoms. One may hope that tests for blood-borne biological markers for v-CJD susceptibility may be developed in the near future, allowing effective blood donor screening.
Legal Disclaimer
This article describes historical or potential exposures and pertinent safety or loss controls of which we are now aware, as well as relevant examples of case law, statutes, and regulations. Not all exposures, losses, or loss controls are reported and others may be relevant in particular circumstances. This material may need revision from time to time, but we do not undertake to do so. We encourage you to consult with appropriate professionals including legal counsel and to obtain the original texts of materials referenced with respect to the matters discussed herein. |
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