Mad Cow Disease - an historic meeting

29 April 1991

A Meeting held at the Linnean Society, Burlington House, Piccadilly.

1: Video presentation: "BSE and its manifestations"

2: "An Historical Account of BSE and other Spongiform Encephalopathies in Animals and Man" - Mr Ray Bradley, Central Veterinary Laboratory, New Haw, Weybridge, Surrey KT15 3NB.

3: "Current Facts in the Context of Scrapie" - Dr Chris Bostock, Institute for Animal Health, Compton, Berks RG16 ONN.

4: "Political and Presentational Aspects of BSE" - Mr R C Lowson, Ministry of Agriculture, Fisheries and Food, Toby Jug Site, Hook Rise South, Surbiton, Surrey KT6 7NF.

Chairman, Brian J Ford (Chair of the History of Biology, Institute of Biology, London).

The impact of BSE was clear from the response of the audience to the first individual to appear in our one-day meeting. She was Daisy, a Friesian suckler cow aged six years. We watched her clinical deterioration, along with the case histories of four other cows. Her uncoordinated gait and poor bodily condition were reflected in an agitated and nervous manner. She frequently tried to rub her head, either with a front hoof, or against a wall; and later lost normal walking movements. The video-tape recording these clinical manifestations was the opening shot by Ray Bradley, Head of the Pathology Department at the Central Veterinary Laboratory at Weybridge, Surrey. It provided a graphic illustration of the nature and implications of the disease from the agricultural and veterinary viewpoint.

The disease was clinically recognised during 1985/6. It has an incubation period that seems to range from between 2 and 8 years, and seems to have been related to the feeding of meat and bone-meal to calves. The brain develops large vacuoles, giving it a spongy appearance. The timing of our meeting was intended to reflect the hoped-for peak in the incidence of BSE, for - if current practices are to be relied upon - the numbers should from now on steadily decline. History is too often confined to the distant past; but we have transient phenomena occurring in our present-day experience and it seemed timely to adopt a generally historiographic approach to a disease whose history occupies the past few years.

Ray Bradley opened by stating how fascinating he had found the opportunity to research the history of the spongiform encephalopathies for the meeting. The Institute of Agricultural History in Reading had provided some early literature from the 1700s, and Mr Bradley said he now lacked only the slides of Drs Jacob and Creuzfeld, whose work on spongiform disease in man had led to its recognition as a clinical entity. Scrapie is the earlier disease of sheep and has been documented for centuries, and has itself been given a variety of names - rickets, distemper, and others.

From 1759 it was known as 'trotting disease' to German workers, in 1811 the French knew it as the 'malady of madness and convulsions', and is more recently known as La Tremblante. Even the condition grandly known as Paraplexia Enzootica Ovium is scrapie in reality. Other descriptions from as far afield as Hungary and Iceland were noted.

1732 is the date provided for the earliest clinical recognition of the disease in Britain; but it was the beautifully printed article by Leopold in Germany in 1759 which gave the definitive description:

"Some sheep also suffer from scrapie, which can be identified by the fact that the animals lie down, bite at their feet and legs, rub their back against posts, fail to thrive, stop feeding, and finally become lame ... This distemper is incurable. The best solution, therefore, is for the shepherd to dispose of a suffering sheep quickly, slaughtering it away from the manorial lands. A shepherd must isolate such an animal away from the healthy stock immediately, for it is infectious and can cause serious harm in the flock."

Parry's book on scrapie describes precautions recommended during the late eighteenth century, and Mr Bradley explained how the early suggestions matched reasonably with the current understanding of scrapie management. The disease, he pointed out, was the first spongiform encephalopathy to be recognised, and he drew attention to the fact that the finest description came from Germany, "a country which now claims to have no cases of scrapie," he added.

In 1799 the Bath and West of England Society journal published an account of the diagnosis of scrapie in sheep. And shepherds were later enjoined to prevent the ewe from devouring the placenta after birth, practice, Mr Bradley said, now followed by farmers raising cattle. In 1789 the Highland Society published a detailed account of sheep which showed scrapie was still absent from that region; it was noted for the first time in 1850. But there was a case of 'scrapie' in cattle to which reference was made in the nineteenth century, and Mr Bradley is still hoping to find the original, just in case it points to a genuine case of BSE. Berger in 1829 published an account in France which seems to parallel BSE in many respects, and in 1848 it was suggested that scrapie was a mental degeneration caused by sexual excess, or possibly by lightning discharge.

1899 was the year in which the vacuolation of the brain was first noted by microscopy; this was in France and indeed French and German work dominated the field into the present century. Sarcocystis was identified as a parasite of cattle and pigs (rarely of man) but usually causes no disease in the host. The trophozoite can rarely enter the brain or pancreas and cause symptoms. The relationship of this condition to scrapie was discussed. Small cysts are formed, with no tissue inflammation surrounding them; rarely they can be found in the brain and it is always possible that this organism could transmit the agent of BSE.

The Principal of the Royal Veterinary College in 1918 carried out a series of experiments on transmission, and did much microscopy on the internal organs from scrapie victims. His transmission experiments were largely negative, though he recognised the lengthy incubation period and described it as a problem which needed to be addressed. Subsequently, other workers discussed the safety of eating scrapie mutton and the first attempts were made to quantify the problem in economic terms. Sir Stuart Stockman in 1926 claimed to observe the recovery of severely affected scrapie sheep, and he also said there were no brain lesions (though he did report some in the spinal chord and medulla, almost a contradiction, Mr Bradley pointed out). No recovery has been documented since; the disease is regarded as lethal.

The first transmission of scrapie was demonstrated in 1936 by inoculation, and shortly after a spongiform disease in humans was described. This was inherited as an autosomal dominant disease; it remains very rare. In 1937 the first reports were published on the histopathology of scrapie lesions, and in 1942 scrapie was reported to occur naturally in the goat. It was found that the agent was highly resistant to heat, to disinfectants (like formalin), and the view began to arise that the scrapie agent was not a conventional virus. A large experiment took place in 1957 which involved large numbers of sheep: it became known as the 'Twenty-Four Breed Experiment', and was later described as 'audacious'. It established that the genetic susceptibility to scrapie varied with the breed. A massive inoculation was undertaken on a single day into between 30 and 57 sheep of each of 24 breeds, a total of 1,027 sheep in total, all inoculated (either cerebrally or subcutaneously) by hand. The sheep were kept for two years and scrapie carefully recorded. Scrapie was also transmitted to both sheep and goats via infected placenta. Moving to 1954, we find a leading Icelandic experiment which gave rise to the concept of the 'slow virus' infections. Scrapie was among those studied. Also in the 1950's came the rival view that scrapie was a disease, not of the brain, but of muscle. Microscopy was used to confirm the suspicion. But a detailed study in 1958 showed that, for all the myopathy, the disease was primarily that of the nervous system.

Kuru was described in 1957 among the cannibals of Papua/New Guinea living in the eastern highlands. Early suggestions were that the disease was transmitted from pigs, but experimentation showed this was not tenable. Later it turned out that cannibalism was rife, and that this led to the disease. Scrapie and kuru were drawn together in a paper for the Lancet and this gave rise to experimental modelling of kuru which gave rise to the award of a Nobel Prize for Medicine for 1976. In the late 1970s and early 1980s further experiments with kuru and scrapie showed that interspecific infection was possible, and since the middle 1980s, BSE has fitted into the pattern. It is noteworthy that, as BSE is almost entirely confined to Britain, there are large areas of the world where scrapie is absent. Most notable are the tracts across Asia and the whole of Australia and New Zealand, from which the disease remains absent.

This points to the unlikely correlation between Creuzfeldt-Jacob Disease, CJD, and scrapie; the incidence of CJD is as high in the scrapie-free nations as it is in Britain. Dr Chris Bostok spoke after the luncheon, addressing the state of our current knowledge of BSE in the context of earlier work. He emphasised that BSE is just one of many identifiable spongiform encephalopathies, and raised the question of the 'naturalness' of these diseases. Was BSE natural? Or has it been transmitted to cattle artificially? It was important to examine the properties of the disease and the agent responsible. Though there are some forms of antigen produced by the agent, anti-scrapie antibodies are not produced in the infected sheep, and there is no immune response to the condition. There is a protein deposition in the form of small fibrils called prions. It was previously felt that the prions were the causative agent itself, but now we understand them to be the manifestation of the disease process, rather than its cause.

Amyloid plaques may be demonstrated in infected brains, and the microscopical appearance can be related to the strain of scrapie under study. Most infectious diseases are caused by bacteria, viruses or parasites: but the BSE agent is not a conventional microorganism. Its extreme resistance to destruction puts it into a different category altogether. Two theories have evolved: one is that the agent is a 'sub-virus', known as the virino hypothesis. The alternative view is that it is an infectious protein which arises from the host animal itself. The latter view is highly contentious, and the history of the subject has yet to clarify the most likely explanation.

Although earlier studies had shown that the incubation period could be very long, it was now known that the time was predictable - with a few days either way, even for the longer periods. Scrapie agent can be inoculated into mice and maintained for several generations. It provides a testable source of the agent. Work at Edinburgh has now identified some twenty different strains of scrapie. This in itself may suggest that the agent must have a genetic component of its own. The laboratories at Weybridge and Edinburgh cooperated on work with BSE on strains of mice selected for short and long incubation of scrapie. The results suggested that the genetic composition of mice with regard to incubation period was more complex than earlier workers had tended to conclude.

Interestingly, the plaques showed optical activity under the polarising microscope, thus showing that a zone of ordered protein molecules was being produced. Attention has recently been paid to the structure and composition of this protein. It has been speculated that this protein contains the infective agent, but of course since the time of Koch in the 1870s we have been aware of the possibility that an unsuspected contaminant is coincidentally present. However, tests for the presence of specific proteins are now being used as a diagnostic test for BSE. In particular, PrP in scrapie has been widely studied in sheep and may be associated with the genes regulating incubation period in sheep. Bovine PrP is currently under investigation, in the hope that it may offer a laboratory test for BSE before the clinical manifestations become apparent.

But there are many conceptual problems remaining, notably the relationship between a novel disease of this sort and the possibility that new mechanisms of infectivity may be recognised for other recalcitrant conditions. It may be that foreign proteins could, in some fashion, induce the development of a novel disease agent - a point raised during the discussion period - and Ray Bradley added some examples of the great complexity in the epidemiology of scrapie which had emerged over the years. He added that the strains previously known to be resistant may now be manifesting scrapie more than they did. A further opportunity for control of an agent might have been the use of heat recovery of solvents used to extract fats from animal feeds until the middle eighties, and one was tempted to speculate whether the dropping of that practice had allowed an agent to survive for the first time. Dr Bostok said the view was intriguing, and laboratory work was under way to relate foodstuffs processing to the infectivity of the product.

The role of official policies was examined by Mr R C Lowson, who had studied constitutional history at University and saw interesting parallels between the retrospective assessments applied to ancient history and the sharpening of one's faculties that was necessary when dealing with matters of more recent origin. November 1986 was the date when BSE was officially recorded, when a series of risk factors came together - arguably since the early 1980's - with the results now evident. Mr Low son said that the development of the subject, its history as it were, had led to the adoption of policies which should lead to a reduction in the incidence of BSE within a year or so.

In one respect it could be argued that BSE was a 'media event', and owed much to the current interest in food safety generally. Yet the question remained: was the topic a matter of public concern because it was in the media, or was it featured in the media because it was a matter of legitimate public concern? It is noteworthy that foods which become the centre of media stories often take a long time to regain their sales level, whilst beef had recovered more rapidly than had been expected. There is, Mr Lowson said, a core of journalists who make their living by reporting food scares, and it would be unreasonable to hope that they would publish articles emphasising that matters were under control. Already-existing hazards are accepted readily, he said; new risks acquire much more prominence. The matter is further confused by the ignorance by the public of what their food consists of - for many the BSE reports were the first indication that the beef they consumed was not raised on a diet of meadow grass. The government needed to balance the safety of the public with the need to maintain a vitally important industry, and scientific opinion was sought to aid this 'balancing act'.

There is a real need to have a body of opinion that can make sensible recommendations on the basis of current knowledge, objectively examined. The fundamental aim should be to keep the risks to the public to an irreducible minimum, bearing in mind that we are working in an area devoid of absolutes, and where value judgements are necessary.

During discussion the point emerged that the government seemed not to have heeded the lessons of history at all. In the early phases of BSE, for instance, the term 'scrapie' was officially extirpated from discussion. This may have been counterproductive. Later, compensation for farmers was only nominal, and cattle must have been sold on when the disease became apparent, in order to avoid the lower value of knackering the beast. The viewpoint advanced was that the government did offer the market value eventually - but for some years that was not the case, and during that period the disease might have spread further because of the reluctance to compensate fully.

Perhaps the greatest single lesson of the affair was that scientific advisers and government policy-makers needed more historical perspective in handling such matters when they arise. Cost should not constrain urgent action when such problems arise, and the lessons of BSE may yet point the pathway to speedier and more efficient official action in the future.

After the meeting there was a broad range of feedback from those who had attended. The interview with the Meeting Chairman about the meeting on TV AM that day had been seen by a number of people, and pleasure was expressed at seeing the History Committee raising its head in such a public medium. All felt the application of a retrospective theme to a topical subject had been timely, and many comments were made about the purely social aspects of meeting over lunch. It was pointed out that the Institute as a whole rarely organises such events (the AGM being the only example at present), and this was felt to be a useful pointer to how the parent body should progress in the future.

The meeting was followed by the Group's Annual General Meeting, at which these points were raised; and many of those who attended were taken down into the Linnean Society's basement and given a tour of the Linnaean collections, to set the seal on the historical tone of the day.

Brian J Ford

Go to diary of writing the book, the bibliography, or the book details.