BSE in U.S Cattle -- Scientific Papers of R F Marsh

UW SCIENTIST SAYS MAD COWS ARE NO JOKE

Capital Times ... March 23, 1996
By: Mike Ivey The Capital Times

The TV footage this week of sickly, flopping cows being fork-lifted into incinerators was enough to turn the stomachs of even occasional Quarter-Pounder eaters like myself. It's also the last thing the beleaguered U.S. beef industry needs, new research out of Britain showing a link between ``mad cow disease'' and a similar fatal brain disease in humans.

Even comic Jay Leno found the story of British ``mad cow mania'' made ripe fodder for his own brand of timely humor. ``Two jokes on mad cow disease in one night, unbelievable,'' said Richard Marsh, a University of Wisconsin veterinarian and animal health specialist.

But Marsh will take the publicity wherever he can find it. He's been sounding the alarm over mad cow disease for years -- and fighting USDA officials who say his concerns are unfounded in this country. Marsh is one of the nation's top authorities on bovine spongiform encephalopothy (BSE), the scientific name for mad cow disease. It's called mad cow disease because it attacks the brain of cattle, causing seizures that makes it appear the animal is crazed. It's always fatal.

Marsh coordinated a conference on BSE in Madison in 1993, the first of its kind held in the United States. And he's continued to follow the issue closely through the European and scientific press. While no cases have yet surfaced here, mad cow disease has proven a legitimate threat to the beef industry in British, where 900 to 1,000 cases a week were reported in 1992-93. That has since declined to about 300 cases in January of this year.

The concern now is that eating meat from diseased cows can lead humans to develop Creutzfeldt-Jakob Disease (CJD), a rare brain ailment that usually affects older men, often mimicking Alzheimer's disease. Ten new cases of Creutzfeldt-Jakob Disease have surfaced recently in people under age 42 in Scotland, leading researchers to suspect a link does exist between the human and animal versions. The British Health Minister said Wednesday that consumption of beef years ago was ``the most likely explanation'' for the outbreak.

In the U.S., concerns over mad cow disease have been limited to Marsh and a few members of the anti-beef crowd, including activist Jeremy Rifkin. Marsh, himself a beef-eater, maintains his interest in the issue is limited to worries over animal health. But he says anything that gets people to pay attention to the threat to U.S. livestock is OK.

``I hope this will be the impetus to get the USDA to take a stronger look,'' he says. The immediate problem, says Marsh, is that many farmers today supplement cattle feed with meat and bone meal, usually made from cattle and sheep. The high-protein feed is said to raise growth rates and milk production. But feed made from sheep bones can transmit scrapie, a degenerative nervous disease in animals that is similar to BSE.

Marsh has called for a ban on animal-based protein supplements or requirements to label those products. He says soy or fish-based protein supplements are just as good, and much safer. But those efforts have met strong opposition from the livestock industry.

``You'd be surprised at the pressure these commodity groups can put on regulators,'' he said.

Well, not too surprised. The U.S. beef industry has long benefited from corporate welfare in the form of taxpayer subsidies for grazing and water. That's why McDonald's and Hardee's can sell their hamburgers so cheap. Price, after all, has little to do with good taste.

BSE in U.S Cattle -- Scientific Papers of R.F. Marsh

Robinson, M. M.; Hadlow, W. J.; Huff, T. P.; Wells, G. A. H.; Dawson, M.; Marsh, R. F.; Gorham, J. R. Experimental infection of mink with bovine spongiform encephalopathy. Journal of General Virology 1994 75 9 2151-2155

Standard dark mink were inoculated with coded brain homogenates from 2 British cows affected with bovine spongiform encephalopathy (BSE) or a third cow from a farm with no history of BSE or feeding ruminant-derived, rendered by-products. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the 3 was fed to a fourth group. Neurological signs were seen in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the main clinical signs, quite unlike the classical clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of scrapie-like spongiform encephalopathy. Vascular change in grey matter neuropil was accompanied by prominent astrocytosis. Varying markedly in severity from one mink to another, the degenerative changes were found in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brain stem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. These results extend the host range of the BSE agent and show for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.


McKenzie, D. I.; Cowan, C. M.; Marsh, R. F.; Aiken, J. M. PRP gene variability in the US cattle population. Animal Biotechnology 1992 3 2 309-315

Variation in the primary amino acid sequence of prion protein (PrP) has previously been found to be associated with changes in the incubation period of subacute spongiform encephalopathies. The PrP gene from 65 cattle representing 14 breeds was analysed by the polymerase chain reaction and restriction fragment length polymorphism analysis. Two PrP alleles, differing in the number of octapeptide repeats, were found. The predominant genotype was homozygous for 6 octapeptide repeats. Few individuals (8) were found to be heterozygous for these repeats, and only 1 animal was homozygous for the 5 octapeptide repeat allele.


Marsh, R. F.; Bessen, R. A. Physicochemical and biological characterizations of distinct strains of the transmissible mink encephalopathy agent. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 1994 343 1306 413-414

Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA. Inoculation of the Stetsonville, Wisconsin source of transmissible mink encephalopathy (TME) into Syrian hamsters has identified 2 strains of the TME agent having distinct biological properties and producing disease-specific prion proteins (PrP) having different physicochemical properties. Although several strains of the sheep scrapie agent have been identified in Great Britain, this is the first indication that agents producing transmissible spongiform encephalopathies in the USA also are capable of producing distinct strains.


Bartz, J. C.; McKenzie, D. I.; Bessen, R. A.; Marsh, R. F.; Aiken, J. M. Transmissible mink encephalopathy species barrier effect between ferret and mink: PrP gene and protein analysis. Journal of General Virology 1994 75 11 2947-2953

The black ferret (Mustela putorius furo) and the closely related mink (Mustela visa) showed differences in susceptibility to challenge with the Stetson transmissible mink encephalopathy agent: the incubation period was longer in ferrets (28-38 months) than in mink (4 months). Western blot analysis detected no differences between ferret and mink prion proteins (PrP). Northern blot analysis of ferret brain RNA indicated that PrP mRNA abundance is similar in infected and uninfected animals. Comparison of the deduced amino acid sequences of PCR amplified PrP coding regions of the PrP genes identified 6 silent base changes and 2 amino acid changes between mink and ferret: PheLys at codon 179 and ArgGln at codon 224, respectively. These changes may indicate the region of PrP that is responsible for the species barrier effect between mink and ferret.


Robinson, M. M.; Hadlow, W. J.; Knowles, D. P.; Huff, T. P.; Lacy, P. A.; Marsh, R. F.; Gorham, J. R. Experimental infection of cattle with the agents of transmissible mink encephalopathy and scrapie. Journal of Comparative Pathology 1995 113 3 241-251

Cattle are susceptible to experimental infection with the Stetsonville isolate of the transmissible mink encephalopathy (TME) agent. Susceptibility to other TME isolates was investigated in 2 groups of calves inoculated intracerebrally with the homogenate of mink brain containing the Hayward or the Blackfoot isolates. A third group was inoculated with a brain homogenate from a steer infected with the Stetsonville isolate in its primary cattle passage and a fourth group was inoculated with a pool of brain homogenate from the 3 cattle experimentally infected with a sheep and goat scrapie agent in its primary cattle passage. Clinical signs of neurological disease appeared in each steer of every group between 15 and 25 months after inoculation. An encephalopathy characterized by severe spongiform change and pronounced astrocytosis occurred in the 3 groups inoculated with the TME agent. The neurohistological changes in the steers inoculated with the cattle-passaged scrapie agent were slight and subtle. Analysis of the octapeptide repeat region of the bovine protease-resistant protein (PrP) gene showed that variations in incubation period, clinical signs, and neurohistological changes were unrelated to the homozygous or heterozygous condition of 6 or 6/5 octapeptide repeats.