Transmissible spongiform encephalo-pathies (TSEs) have become a household word during the past 15 years, and have destroyed major parts of the beef market throughout the world. Starting 200 years ago in the U.K. with the discovery of with "scrapie," or ovine spongiform encephalopathy (OSE)), in sheep, we have successively discovered many forms of TSEs, including Creutzfeldt-Jakob disease (CJD) in humans; transmissible mink encephalopathy (TME) in minks; bovine spongiform encephalopathy (BSE), or "mad cow disease," in cattle; and chronic wasting disease (CWD) in deer and elk.

The recent event in Canada, where the first native North America BSE case was reported in May 2003, has catapulted this disease from the back page to the front page of newspapers. Quite naturally, consumers have been alarmed, non-tariff trade barriers enacted, Senate investigations initiated and activists activated. Industry continues denial that any problem exists.

What is the significance of these diseases, and is there any real cause for alarm? Are government and industry doing what they should? What risk is there that our food supply is threatened? To understand our current situation and what we should do, we need to understand the context of TSEs in recent history.

"Though This Be Madness, Yet There Be Method In It"
TSEs are interesting diseases: They turn the brain to "Swiss cheese" by creating "holes" of abnormal morphology. As the disease progresses, more and more brain and central nervous system (CNS) tissue is affected. Initial symptoms involve tremors and twitching. Later symptoms include blindness and loss of memory. Death follows. The most familiar spongiform encephalopathy is Alzheimer's disease (Creutzfeldt and Jakob worked at Dr. Alzheimer's institute for brain diseases). It is thought that perhaps 5-10% of Alzheimer's disease cases may be in reality misdiagnosed CJD cases.

TSEs are believed to be caused, or at least propagated, by misconformed proteins called "prions," which somehow "trick" properly conformed proteins to switch to the abnormal conformation. The conversion results in the amyloidal plaques that give rise to the "spongy" morphology of the brain tissue. How this mechanism works, and whether it is the sole answer to infectivity, is not well understood and is the subject of Nobel Prizes and significant research. We do know that TSEs affect primarily older animals, as it takes significant time to amplify prions and generate clinical symptoms. CJD, the TSE of humans, primarily effects the elderly.

A nasty property of prion diseases is that the misconformed protein is not susceptible to enzymatic proteolysis (as in digestion) and are not easily denatured by heat (as in rendering) or by chemicals (as in sanitation). Consequently, they survive common disinfection techniques. Many cases of CJD in humans have been caused by reuse of neurosurgical instruments.

The United Kingdom: Mad About Ewe and Cattle, Too
Some 200 years ago, Scottish shepherds noticed an unusual nervous system disease they labeled "scrapie," as the sheep frequently rubbed themselves against fences, trees or other objects because their nerves generated phantom itching feelings. The disease was invariably fatal, and was found to be horizontally transmissible via placenta and other mechanisms. For the last 50 years scrapie-infected flocks have been eradicated whenever they have been found. Scrapie is endemic to most sheep-farming countries (including the U.S.), except for island countries such as New Zealand and Australia.

In 1986, a U.K. veterinarian reported a cow with suspicious CNS symptoms to the Weybridge veterinary laboratory for investigation.[1] The animal was found to be infected with a new TSE, dubbed BSE for bovine spongiform encephalopathy. Luckily, the U.K. had funded a substantial research program into scrapie after World War II, so the disease was easily recognized as spongiform encephalopathy by investigators. Subsequent epidemiological modeling has indicated the index case probably occurred in the late 1970s, but amplification was required to raise the level of incidence to the point that veterinarians would encounter a symptomatic case, as they did in 1986. The cause of the index case was never discovered, with hypotheses ranging from a hidden variant of scrapie in sheep to imported African MBM to random mutations ("Gibbs hypothesis").

Amplification was easy to come by in the U.K., as the industry was feeding 10% or more meat-and-bone meal (MBM) to young cattle, and recycling CNS tissue in the process. BSE was found transmissible orally, with one gram or less of CNS tissue in an oral one-time dose giving rise to a high probability of disease. One cow's brain and spinal cord was capable of infecting hundreds of others when fed back through MBM to other cattle.

In July 1988, a ruminant-ruminant feed ban was enacted to eliminate amplification via feedback. This crucial step was the key to controlling BSE, but its result was not felt for five years, the mean incubation period for the disease. In 1992-1993, at the peak of the epizootic in the U.K., there were more than 30,000 BSE cases per year discovered by clinical referral and laboratory confirmation in a total cattle population of about 10 million.[1] As an example of the pervasiveness of the disease, the Isle of Guernsey incidence rate was an amazing 33% of adult animals per year in 1993![2]

With the usual governmental and industrial laxity, the U.K. exported throughout the world the contaminated MBM they did not allow to be fed to their own cattle. BSE cases started appearing in other countries in the European Union (EU), starting with France and Ireland and progressing to almost all other countries in Europe. The EU imposed a feed ban in 1997, but most countries are still in the midst of expanding epizootics. The political effect of country after country discovering cases of BSE after years of denial has demolished confidence in government and industry and forced the institution of 100% surveillance by biochemical testing of all adult animals slaughtered. In 2002, more than 10 million such animals were tested with some 2,000 positives found.[3]

Complicating the situation was the discovery that BSE was implicated in a new form of CJD, dubbed "variant-CJD" (vCJD), which affected primarily young adults and has claimed more than 130 lives to date.[4] The reason for the connection is still not clear, but is presumed to be related to consumption of beef CNS tissue or medical injections of bovine-based vaccines or other pharmaceuticals.

A Mad, Mad World for Minks, Deer and Elk
About 20 years ago, Wisconsin mink farms were decimated by TME in repeated epizootics for which the root cause was never discovered. The chief investigator, Dr. Richard Marsh, conjectured that scrapie-infected sheep initiated the outbreaks, but this does not appear to fit the high attack rates observed.[5] A more logical explanation would have been mink-to-mink feeding, but this activity was uniformly denied by the mink ranchers involved.

In 1967, at a capture-and-release research station in Fort Collins, CO, wildlife researchers reported that young deer were dying from an unknown "wasting" disease. By 1978, the new disease had been dubbed chronic wasting disease and had been found to be a TSE of cervids. As time has passed, CWD has been found to be an endemic disease of mule deer, white-tailed deer and elk in Colorado and Wyoming. Incidence is as high as 15% of deer in some areas.

Unfortunately, a burgeoning industry in elk antlers for export to the Far East and game farms for hunting created a substantial and unregulated trade in breeding stock for elks and deer that moved animals freely between the states and between the U.S. and Canada. As a consequence CWD has spread to new geographical areas over the last few years, now being firmly entrenched in places such as Alberta, Saskatchewan, Oklahoma, Minnesota and Wisconsin. States as far east as Pennsylvania and Virginia are now surveilling deer herds for CWD.

CWD has a horizontal mode of transmission, conjectured to be similar to that of scrapie. It apparently can cross double-fenced enclosures and transmit by casual contact between animals. The Fort Collins research facility has removed the topsoil from penned areas, but new animals still mysteriously contract CWD when introduced into the area. As CWD has decimated the export trade for elk antlers, impoverished ranchers have released animals into the wild, further compounding the spread of the disease. The number of cases of CWD occurring annually is not apparently available to the public at the current time, but must number in the ten-thousands in a national cervid herd of perhaps 30 million in the U.S. alone. The CWD epizootic currently taking place in North America rivals or exceeds the size of the BSE epizootics in the U.K. and EU.

Except for hunters and ranchers, few people seem concerned about this raging epizootic of CWD. Governmental budgets for coping with the disease probably don't exceed $20 million in total for both the USA and Canada. Only within the last year have regulations been promulgated affecting the interstate transfer of possibly diseased animals. (The recent monkeypox outbreak illustrates the lack of regulatory oversight in the importation and movement of non-food animals.)

Mad Canadians
Following the U.K. and EU experiences with BSE, the U.S. and Canada imposed a ruminant-ruminant feed ban in 1997 in order to break the feedback loop in the event of introduction of BSE to North America. This ban was later extended to "mammalian"-ruminant feedback, although "mammals" for this purpose apparently do not include pigs and horses![6] This ban also had the effect of blocking recycling of CWD-infected deer and elk from entering the cattle feed supply.

Up until the present year, the only BSE cases found in North America were traced to importation from the UK, and the animals had been controlled by quarantine. However, at the end of January 2003, a six-year-old cow sent for slaughter at a province-licensed packer in Alberta was found to exhibit unusual and possibly CNS-based symptoms. The cow was a "downer" (i.e., could not stand) and was wasted. The animal was condemned and the brain was forwarded the provincial veterinary laboratory for TSE testing, with a presumptive diagnosis of pneumonia. Because of the raging CWD epizootic (5,000-plus samples per year in Alberta), the laboratory back-shelved the suspect animal's brain in favor of meeting CWD test schedules. It wasn't until May 16 that the sample was tested and found positive for BSE. The diagnosis was confirmed again at the Canadian Food Inspection Agency (CFIA) and finally at the U.K. Weybridge on May 20. So after a delay of nearly four months, Canada had discovered its first native case of BSE.

Immediately reactions occurred affecting exports of Canadian beef and cattle. The U.S. closed its borders to the substantial trade (some 1.7 million live cattle per year) and other countries in the Far East stopped all imports. Within days the Canadian beef industry had lost major markets. In the month following the announcement of the BSE case, some 2,700 cohort animals have been eradicated and tested. All were found negative. No cause has been found for the BSE case, but the presumption is that the age of the animal is consistent with ingestion of contaminated MBM prior to the feed ban of 1997 (or rather its effective implementation in 1998), or possibly from feed ingredients imported from the U.K. or EU.

Animal raisers and packers in Canada are angry with the U.S. and other countries for keeping their borders closed to Canadian animals and beef. Obviously, such moves benefit the domestic beef industries at the expense of the Canada's. Canadians feel that the uniformly negative results on the 2,700 eradication-cohort animals proves that the observed case was an isolated event, and no scientific grounds exist for keeping the borders closed. Alberta lobbyists have even gone to the extent of enlisting Vice President Cheney's aid in forcing the U.S. Department of Agriculture (USDA) to remove the import bans. The political consequences and non-tariff trade barriers resulting from the Canadian BSE case have even extended to the hot-debated "country-of-origin-labeling" law and U.S.-Japan trade.

The U.S.: How Mad Can We Get?
Clearly the 1997 feed ban, if strictly enforced, would basically eliminate amplification in North America, so the risk of BSE is limited to single or small clusters of cases. An epizootic of the scale of the U.K. BSE or CWD types is no longer possible, as five years have now elapsed since the feed ban was imposed. A beneficial factor is the shorter lifetime of cattle in North America, as compared to Europe: Cows rarely are allowed to live more than about eight years here.

TSEs are more properly viewed as intoxications rather than infections. The key issues are: (1) how much toxin is fed to an animal; and (2) how long it will take for clinical symptoms or test-sensitive doses to appear? The infectious nature of TSEs lies in their transmissibility and the ability to amplify the toxin within the body over time. Because of the feed ban and the shorter life of cattle in North America, and because grain is cheap here, the dose of BSE delivered to animals in the U.S. is much smaller than that in the EU, and less amplification occurs during the shorter lifetimes. So even if BSE toxin was present in feeds in North America, it is not necessarily true that very many cases would ever be detectable, even with biochemical testing. Furthermore, the five years that have elapsed since the feed ban was imposed limits the large-scale risk solely to five-year or older animals.

For all of these reasons, a large-scale epizootic of BSE in the U.S. is highly improbable, and in any event, would be limited in duration to only a few years before it naturally phased out because of the 1997 feed ban. On the other hand, there are still several short- and long-term issues that must be resolved to preserve the economic safety of our cattle and beef industry. The first question that has to be dealt with is whether or not the BSE situation in Canada remains a threat to the 100-million-strong U.S. cattle herd. Should we open our borders to live animal transfers again? Unfortunately, the actions taken by the Canadian regulators mean little more than a BSE case has been discovered there. The testing of the 2,700 eradication-cohort animals supplies only the weakest of scientific evidence of absence of further BSE-infected animals.

In the EU, where most countries are in the midst of national BSE epizootics with rising case rates, the average incidence in 2002 of BSE in eradication-cohort animals was only 1:3,800.3 This incidence also varies widely from country to country. For example, France, which had 240 cases of BSE found in 2002 by mandated testing, found only one BSE case in nearly 16,000 eradication-cohort animals. This means that Canada would have expected only a 50% chance of finding a BSE positive in the 2,700 tests done so far, even if its BSE incidence were equal to the average of the countries in the EU. If Canada were similar to France in BSE incidence, the chance of finding a BSE case in the 2,700 animals would have been only 16%. So, all we know by the testing done is that BSE in Canada is no worse than that of the typical country in the EU. It certainly does not show, as the Canadian beef industry argues, that there are no further BSE cases present in the national herd of 15 million cattle.

In fact, the very arguments that Canada is making for the isolation of the observed case lead to suspicion that more such cases exist. If the current case were due to birth before the 1997 feed ban and consumption of contaminated feed, then logically, other such animals with similar circumstances should exist. Consequent-ly, all cattle older than perhaps five years in Canada are now suspect for BSE. The logical responses to the Canada situation should be:

* All animals older than five years should be tested for BSE at slaughter and excluded from the human food supply or food animal feed.

* The specified risk materials (SRM), such as CNS tissue, of cattle older than 30 months should be excluded from the human food supply and food animal feed.

* All "risk" animals (i.e., dead-on-farm, emergency-slaughter, sick-at-slaughter, "downer") should be tested for BSE.

* No live cattle older than five years should be exported.

* A system of positive identification tracking of animals with traceback should be instituted to allow rapid and effective response to any new positive results found.

Unfortunately, the border between Canada and the U.S. has been so porous (1.7 million live animals transferred from Canada to the USA in 2002) that for all intents and purposes it would be wise to consider the cattle populations of the two countries as one large herd.

How much confidence do we have that BSE is not present in the U.S.? The current USDA-APHIS surveillance plan instituted in 2002 is based on the following simple argument: The U.K. and EU experience indicates that more than 50% of the cases of BSE have been found in either the "suspect" (i.e., clinical referrals) or "risk" populations. Only animals older than 30 months have ever been found positive for BSE. All "suspect" animals will be tested for BSE. There are about 200,000 to 500,000 "risk" animals slaughtered in the U.S. per year. The U.S. national herd is about 100 million in size, with about 45 million older than 24 months.[7] Assuming that 100% of the cases of BSE occur in the "risk" and "suspect" populations, and a "risk" population of 200,000, then testing 13,000 "risk" animals per year would guarantee at least 95% confidence of finding a BSE case, if the incidence of BSE were 1:1,000,000 adult animals or higher.

The APHIS assumptions are obviously a little too liberal. Assuming a "risk" animal population of 500,000 and 50% of the cases being found in the "risk" population, the number of tests required would have been 66,000-plus per year, greatly exceeding the 20,000 tests APHIS did in 2002 and is doing in 2003. In addition, the APHIS plan is designed only to detect a BSE incidence of 1:1,000,00 adult animals (i.e., >24 months old) and would therefore not reliably detect up to 45 cases of BSE per year.

Another complication is the out-of-control CWD epizootic in the U.S. The implications of CWD with respect to BSE are still not fully known. What is known is that CWD can be transferred intercerebrally to cattle and sheep, so transmission orally is theoretically possible, although not yet observed.[8]

Given the CWD epizootic, the Canadian BSE case, and the only recent imposition of the feed ban, the U.S., like Canada, should take more stringent measures:

* All animals older than five years should be tested for BSE at slaughter and excluded from the human food supply or food animal feed.

* The SRM of cattle older than 30 months should be excluded from the human food supply and food animal feed. So-called "advanced recovery" meat from vertebrae should also be excluded.

* All "risk" animals should be tested for BSE.

* No live cattle older than five years should be exported.

* A system of positive ID tracking of animals with traceback should be instituted to allow rapid and effective response to any new positive results found.

* USDA should substantially increase its budget for TSEs to allow control of the CWD epizootic.

* All deer and elk carcasses should be excluded from human food supply and all food animal feeds.

Testing of all "suspect" and "risk" animals would providence confidence of absence of BSE at least equivalent to direct testing of 50% or more of the 58 million animal total slaughter per year in the U.S., and supply 95% confidence that no more than one or two BSE cases per year could be missed.[9]

What is the U.S. cattle and beef industry's position on the BSE problem? They would like to keep the Canadian border closed to continue to receive a welcome boost in domestic sales. Otherwise, it is reluctant to impose adequate controls or surveillance measures. For example, as recently as Feb. 5, 2003, the American Meat Institute stated that "no scientific justification currently exists to support changes in animal feed regulations proposed by FDA," in response to a FDA proposal to exclude ruminant CNS tissues from rendering.[10] Consumer and anti-meat activists, on the other hand, want wholesale testing of healthy animals at slaughter, even though they are the least likely population in which to find cases.

The real risk of BSE is not to human food safety, but rather to the cattle and beef industry's economic health. Even a few hundred BSE-infected animals a year passing into the human food supply would not likely generate detectable disease. For example, more than 30,000 BSE case rates per year in the U.K. resulted in only 20 to 30 human vCJD cases per year. But even a single case of BSE found would have immediate impact on beef consumption and exports, as Canada has found to its sorrow. Perhaps over the long run, TSEs in animal food will be accepted as a toxin, just as methylmercury is in seafood. With a balanced diet and effective regulations, the risk of disease is small enough to be borne by society and assumed by the prudent consumer.

Robert A. LaBudde, Ph.D., has been president of Least Cost Formulations, LLC, since 1979, and has served on the faculties of several universities through the years among them the University of Wisconsin and MIT. Dr. LaBudde is well known throughout the meat industry for his contributions in the areas of food safety, chemical analysis, quality control and computer formulation. He has published numerous research articles, holds several patents, and has provided consulting services to more than a hundred major manufacturers.

LaBudde has been a Bell Atlantic Scientist, an Associate Referee of the Association of Official Analytical Chemists and a member of the Scientific Affairs Committee of the American Meat Institute. He is a professional member of many technical societies, including the American Meat Science Association, the Institute of Food Technologists and the International Association for Food Protection. He is an active food safety ideologue, and is noted for his strong and sometimes controversial opinions.

1. MAFF. Bovine spongiform encephalopathy in Great Britain. MAFF, Surrey, U.K. Appendix 1. June 1997.
2. OIE. Annual incidence rate of BSE in the U.K. 2003.
3. Eurostat. 2003. BSE testing in the EU, January-December 2002. 2003.
4. U.K. Department of Health. Monthly Creutzfeldt-Jakob disease statistics. June 2, 2003.
5. Marsh, R.F. and R.P. Hanson. On the origin of transmissible mink encephalopathy. In: Slow Transmission Disease of the Nervous System, Vol. 1. Academic Press, NY. ISBN 0-12-566301-3. 1979.
6. Code of Federal Regulations. 21 CFR 589.2000. Animal protein prohibited in ruminant feed.
7. NASS. Cattle report released July 19, 2002. reports/nassr/livestock/pct-bb/. 2002.
8. Miller, J.M. and Hamir. Experimental transmission of chronic wasting disease (CWD) to cattle and sheep. Progress report. June 23, 2003. Private communication.
9. LaBudde, R.A. and M. Hugh-Jones. Implications of BSE testing in the EU with regard to the USA. 2003. Submitted to Prev. Veter. Med.
10. American Meat Institute. Science does not support changes to FDA animal feed rules. 2003.