By Eric Sideman, Ph.D.,
MOFGA’S Director of Technical Services
How quickly an apparently unknown disease can arise and cause widespread fear. The disease is called Bovine spongiform encephalopathy (BSE) but is more commonly referred to as “mad cow disease.” The fear spread worldwide as we watched Great Britain, the only country with a major outbreak, take drastic measures to stop the disease. All nonproductive cattle more than 30 months of age were killed, and more than 900,000 bull calves were culled.
Although BSE was first recognized in 1985 and its pathology reported in 1986, by 1992 the number of confirmed cases was 37,490 – but that was the peak. In 1996 the number of cases dropped to about 7,500, and epidemiologists predict that the decline will continue and that by 2001 the disease will be virtually extinct. However, many people believe that this is a very optimistic prediction and that the epidemic that was contained in Great Britain was a warning of worse situations to come worldwide. Furthermore, almost everyone is wondering what kind of precautions to take to avoid the problem close to home, because mad cow disease does not stop in the barn. It has been associated with a deadly disease of humans called Creutzfeldt-Jakob disease. I wish I could give straight and conclusive advise on what farmers, gardeners and consumers should do, but in my mind all the informa- tion needed is plainly not available yet. The update presented here tells what is known about the disease and how it spreads, but each of us will have to decide on our own farming and eating practices, and whether we want to base them on risk analysis or precaution.
The Diseases
Spongiform encephalopathies include a group of diseases in which spongiform degeneration (sponge-like holes) of the brain and other parts of the central nervous system are seen under microscopic examination (Table I). All of these have incubation periods of months to years and all gradually increase in severity and lead to death. A key characteristic to remember when I mention the agent of transmission is that none of these evokes an immune response. They all share a common non-inflammatory pathologic progress restricted to the central nervous system.
The most common of these is scrapies – a subacute, progressive ataxia (inability to coordinate voluntary muscular movements) of sheep and goats. Afflicted animals lose coordination and eventually become so incapacitated that they cannot stand. They also become irritable and in some cases develop an intense itch that leads them to scrape off their wool (hence the name scrapies). Animals affected by scrapies have been recognized by shepherds for hundreds of years. The condition was once thought to be inherited, but in 1936 experiments showed it to be transmitted from sheep to sheep with an incubation period in excess of a year. Recently, genetic susceptibility has been shown, but controversy still exists about the natural mode of transmission.
Creutzfeldt-Jakob disease occurs worldwide and usually becomes evident as dementia. It has an incidence of infection of about one case in a million people and strikes people around 60 years of age. Most of the time it appears sporadically (sCJD), but about 10 to 15% of the cases are inherited (called familial or fCJD), and a small number of cases are spread inadvertently by the attempt to treat some other medical problem. Epidemiologists have not been able to correlate the rate with any practices. There is no seasonal variation, no geographic clustering (except for areas with large numbers of familial cases), and no change in incidence over recent years. Neither consumption of brains and offal, nor lifetime vegetarianism seems to alter the risk. Neither surgeons, pathologists, butchen nor cooks who have been exposed to blood and uncooked animal products, etc., have increased risk over the general public.
| Table I. Spongiform encephalopathies | ||
| Name | Animal Affected | Cause |
| scrapie | sheep and goat | infection with prion |
| mink encephalopathy | mink | infection with prion |
| wasting disease | western deer and elk | infection with prion of elk and deer |
| BSE | Cattle | infection with prion |
| Creutzfeldt-Jakob disease | humans | inherited germ line (familial) mutation |
| Creutzfeldt-Jakob disease | humans | humans somatic mutation (spontaneous conversion of natural cell protein) |
| Creutzfeldt-Jakob disease | human | infection with prion (variant) |
The BSE epidemic in the United Kingdom has changed this epidemiological picture of a non-transmissible disease. Although there is no risk of transmission of the fCJD or sCJD, a “new variant” of Creutzfeldt-Jakob disease (vCJD) has arisen and is associated with mad cow disease. The vCJD differs pathologically and clinically from the others – notably in that it can afflict comparatively young people. Rather than dementia, vCJD symptoms include behavioral changes and ataxia.
BSE and Transmission of the Disease
By 1997, over 170,000 cases of BSE were confirmed in 34,000 herds in the United Kingdom. The disease was first observed in 1985, when several dairy cows were noted to have become apprehensive, developed aggressive behavior and showed ataxia. The pathological findings included spongiform lesions that resembled scrapies.
The uniformity of the disease and its lesions, the explosiveness of the epidemic, and the wide distribution of cases throughout the UK all pointed to an epidemic with a common source. No evidence was found of lateral transmission from cow to cow. The source has been traced to supplementing the diets of calves and dairy cattle with meat and bone meal produced by commercial rendering plants. The assumption is that the epidemic started when cows were fed material from scrapie infected sheep. Later, as the meat and bone meal contained material from infected cows, the disease spread further.
The onset of the epidemic followed changes in the rendering process in the 1970s, when continuous heating replaced batch heating to conserve oil. Also at this time, due to the decline of the tallow market, hydrocarbon solvents were no longer used to remove tallow. Some argue that the solvents did not reduce the activity of the disease agents anyway, so their removal from the processing procedure had no effect on BSE transmission; further discussion, however, emphasizes that the previously used solvents did not inactivate the disease agent, but removed the agent that was harbored in the nerve tissue.
In experiments, BSE has been transmitted to a variety of species. Infectivity in cattle is limited to brain, spinal cord and retina materials. Infectivity has not been detected in muscle, milk or blood. Infectivity is not carried by a common agent, such as a virus or bacterium – and knowing about the agent is critical to understanding how BSE relates to the new CJD variant.
The Agent of the Diseases
For a long time the spongiform encephalopathy diseases were thought to be only inherited and not transmissible. A number of factors led to this false belief. First was the long incubation time, so transmission was not easily seen. Then, after transmissibility was demonstrated for scrapies and CJD, it was still hard to think of a single type of agent that could explain both the inherited and transmissible forms. Third, typical pathogens (bacteria, virus, etc.) contain DNA, and so are destroyed by ultraviolet or ionizing radiation, alcohol, formalin, and so on. These do not affect the agent of the transmissible spongiform encephalopathies. Only treatments that typically disrupt proteins (autoclaving, phenol, extreme pH) inactivate the encephalopathy agents.
Work in Prusiner’s lab (see references) pointed toward one startling conclusion: The infectious agent in scrapie (and related diseases) is simply protein. Prusiner introduced the term prion, derived from proteinaceous and infectious. Not long after this discovery, Prusiner and his colleagues determined that the scrapie prions contained a single protein, which they called PrP for “prion protein.”
Prions
The explanation of how prions work and how they transmit disease is particularly exciting because it also explains how inherited and spontaneous spongiform encephalopathies occur. After identifying the prion protein as the agent of the scrapies disease, scientists went on to show that normal cells in mammals contain a gene to make PrP, and they do not get sick. They showed that PrP could be produced in two forms, a normal cellular protein that does not generate disease and an aberrant one that does cause disease: spongiform encephalopathy. They termed the disease causing form “scrapie PrP.” Sometimes these are designated “PrPc” and “PrPSc.” The two differ just in molecular shape.
Proteins are long chains of amino acids that are folded and twisted in different shapes. The shape of protein molecules is very important in the way they react chemically. The normal PrP and the scrapie PrP have the same amino acid chains, but are very different in the shape.
The Scrapie PrP, which causes disease, can propagate itself. When it comes into contact with normal PrP, it causes the normal protein molecule to unfold and flip from its usual conformation to the scrapie shape. This change initiates a cascade in which newly converted molecules change the shape of other normal PrP molecules, and so on.
From Scrapies to Creutzfeldt Jacob
Prions from scrapies-infected sheep were able to infect cows by way of bone meal feed supplements. Although BSE has occurred in a number of European countries, the reported incidence has been much lower outside of the United Kingdom and may always be associated with the United Kingdom – presumably because of the high ratio of sheep to cattle there, a high prevalence of scrapie in sheep there, and the previously common practice of intensively feeding meat and bone meal to dairy cattle there. Researchers generally accept that the epidemic hinged on the changes in rendering practices.
The species barrier makes it difficult for prions made by one species to cause disease in animals of another species. The barrier resides in the amino acid sequence of the PrP of each particular species. Transmission of an aberrant form of PrP seems to be based on the similarity of the PrP of the source and the host. The more the sequence of a scrapie PrP molecule resembles the PrP of its new host, the more likely that the host will acquire prion disease.
The attraction of scrapie PrP for cellular PrP having the same amino acid sequence probably explains why scrapie managed to spread to cows in England from food consisting of sheep tissue: Sheep and bovine PrP differ at only seven positions. In contrast, the sequence difference between human and bovine PrP is large. Because the variance is great, the likelihood of transmission from cows to people would seem to be low.
Since the outbreak of mad cow disease in the United Kingdom, about 30 cases of the new variant CJD have been reported there. All were young, had eaten meat in recent years (although one had become a vegetarian in 1991), but none had knowingly eaten brains. However, before the ban that Britain put on the use of offal, brain and spinal cord were often included in sausages. There is now powerful evidence that the causative agents of vCJD and BSE have a common origin, and are different from sCJD – but, how much of a risk is it?
Conclusions
It is very hard to give conclusive, science-based precautions to prevent the spread of these prion diseases because of insufficient data. Changes in farming or eating practices will still have to be based on precaution, and the level of precaution is personal. Some people, for instance, might opt to avoid eating bonemeal or feeding it to animals; some might not use bonemeal or blood meal in crop production. Others may not find enough reason to take such steps. With respect to health and environment, organic growers tend to make precautionary changes in practices rather than making risk-based changes, especially when the science is lacking. Here are some facts that could help.
• Scientists report no mad cow disease in the United States.
• The USDA has banned the feeding of ruminant animal byproducts back to ruminants, as well as the import of products derived from European cattle and sheep. Since American cattle are free of the disease, no ban on offal has been imposed.
• Scientists report no human disease resembling the new variant CJD in North America. However, a Utah man has recently been diagnosed with a terminal CJD-type disease and it is feared that he may have contracted it by eating deer or elk infected with wasting disease of deer and elk (Table I).
• The Center for Food Safety and other groups have filed petitions with the FDA and CDC demanding better monitoring, regulation and study of this family of diseases. They believe that serious loopholes allow some animal refeeding.
• Research has shown that the sheep scrapies prion (and presumably prions from other hosts) can survive in soil for at least three years and maintain infectivity.
It is important to keep a reasonable perspective and not force any severe hardships on producers and consumers based on speculative comments. On the other hand it would be unwise to ignore this potential calamity. I must close with the classic ending: “More research is needed.”
References
Anonymous, “Advisors Between a Rock and a Hard Place,” Nature 395:1, September 3, 1998.
Brown, Paul, “On the Origin of BSE,” The Lancet 352:252-253, July 25, 1998.
Brown, Paul and Carleton Gajolusek, “Survival of Scrapie virus after 3 year’s internment,” The Lancet 337:369-70, 1991.
Johnson, Richard and Clarence Gibbs, “Creutzfeldt-Jacob Disease and related Transmissible Spongiform Encephalopathies,” New England Journal of Med., P.1994-2004, Dec. 31, 1998.
Nathanson, Nel, John Wilesmith and Cristian Griot, American J. of Epidemiology, 145:11:959-969,1997.
Prusiner, S.B., “Prions,” Proc. Natl. Acad. Sci., 10:13363- 83 Nov. 10, 1998.
Prusiner, Stanley B., “The Prion Diseases,” Scientific American, January 1995.
