THE WORK OF CUILLE AND CHELLE, now fully confirmed by British researchers, indisputably established that scrapie was transmissible. Once introduced into an animal's body, the causative agent multiplied, so that after the proper incubation period the tissues of the animal could be used to infect other animals, and so on. But was scrapie contagious? Was it transmitted spontaneously from animal to animal?
MacFadyean's observations seemed to demonstrate that it could be: Think of Mr. A (introduced in Chapter 4), whose flock had been contaminated by ewes bred by Mr. X. Many similar observations had been published in the scientific literature. Yet there remained room for doubt. It was always hard to be sure whether, had they been isolated, the animals thought to be contaminated by other animals might not have contracted scrapie anyway. Such doubts were fueled by the nearly constant failure of attempts to observe contagion in controlled conditions. This problem too was tackled by British veterinary scientists.
First of all, here are the results of experiments published by Iain Pat-tison in 1964: Seventeen Cheviot sheep (a breed susceptible to scrapie) were kept in a shed for fifty-five months in close contact with a series of sheep and goats infected with scrapie that had been transmitted to them by inoculation. None of the Cheviots contracted scrapie. Nor did the disease appear in any of the 192 goats similarly kept in contact with animals with laboratory-transmitted scrapie. Finally, thirty-three kids— the offspring of three male and twenty-seven female goats inoculated with scrapie at the time of conception—were kept in close contact with their parents, including suckling by their mothers, and showed not the least sign of scrapie four years after birth. How could these negative results be reconciled with the many observations of contagion in normal farm conditions?
Pattison, who worked at the Agricultural Research Council's institute in Compton, undertook a new series of experiments in collaboration with colleagues from the Moredun Research Institute in Edinburgh. This time, the outcome was more conclusive. In two experiments, seventeen goats, from birth, were kept in close contact for extended periods with sheep that had contracted scrapie by natural means. Ten of them came down with the disease. Moreover, three cases were observed in blackface sheep that for about four years had been kept in close and sustained contact from birth with sheep of various breeds that had natural scrapie. Blackface sheep were supposed to be completely invulnerable to scrapie in natural conditions. This was thus an unambiguous case of contagion.
Why did these two series of experiments have such contradictory outcomes? Could there have been uncontrolled differences between the facilities at Compton, where the first series had taken place, and those at the Moredun Institute, which was the site of the second? There could have been other reasons as well. Specifically, the animals used in the attempt to contaminate the others had contracted scrapie experimentally (by inoculation) in the first instance and naturally in the second. Perhaps the two types of scrapie differed in their ability to be transmitted by contagion.
In any event, contagion was observed in the second experiment, which confirmed the many field reports from farmers and veterinarians. Yet, not everybody was convinced. One of the top scrapie specialists, H.B. (James) Parry, continued to believe until his death in 1980 that scrapie could be transmitted only by inheritance. Furthermore, in an excellent book published as recently as 1998, two other specialists, Rosalind Ridley and Harry Baker, expressed doubt that scrapie was transmitted within flocks, and defended the notion of its exclusively genetic origin.1 Still, the great majority of researchers endorsed the idea that scrapie was a contagious disease, even if the contagion is weak. Exactly how the contagion occurred, however, remained to be discovered.
How did the "virus" enter animals in natural conditions? One common entry point for infectious agents is the mouth. Richard Chandler had shown that oral contamination, although inefficient, was possible in mice. What about sheep and goats? Pattison and Millson had asked that very question in 1961, even before Chandler began his experiments. By feeding sheep and goats a drink containing crushed matter from the brains of sick animals, they succeeded in transmitting the disease. Out of fifty sheep of various breeds that had been fed this strange brew, seven contracted scrapie in the following eleven months. So oral contamination was possible. But was it responsible for natural contagion?
It was not until two decades later, in 1982, that a group of American researchers found evidence to support that theory. William Hadlow and his colleagues studied a group of Suffolk sheep belonging to a flock greatly affected by scrapie, their aim being to learn the distribution of the infectious agent in different tissues and to see how this varied according to the animals' ages. They sacrificed animals in various age groups with a view to finding the agent during the disease's development phase and seeing where that agent resided.
In fourteen lambs under eight months of age, they found no trace of the infectious agent in the tissues they analyzed when they inoculated mice with those tissues. On the other hand, they detected it in eight out of fifteen lambs aged ten to fourteen months. In these cases it was present only in the intestine and in the lymph nodes; most of the infected lymph nodes were those near the pharynx and the intestines.
In a group of three animals aged twenty-five months, the infectious agent was found in one ewe. It was located in the digestive tract, including the colon, and throughout the lymphatic tissues, and was beginning to make its appearance in the nervous system, although in low concentrations. No nervous system lesions were visible at this stage, and the animal displayed no clinical symptoms.
Obviously, the infectious agent was found in the nine sheep, aged thirty-four to fifty-seven months, that displayed symptoms of scrapie. The highest concentration was found in the nervous system, although it also infected other organs, including the intestines. And finally, no sign of the infectious agent was found in seventeen adult sheep that displayed no symptoms—although it might have been possible that the disease was in its incubation period.
So, given that the digestive tract and nearby lymph nodes were the first to be affected, infection seemed to take place orally. It then spread to the nervous system via the lymphatic tissues. Infection was more likely among young animals; the infectious agent was found in half the lambs aged ten to fourteen months but in no healthy animal older than thirty months. Moreover, its presence in the intestines throughout the course of the disease suggested that the agent would be found also in the stools, which would then play a role in transmission. That hypothesis has yet to be proved, however; all attempts to find the infectious agent in fecal material have thus far failed.
But Pattison and his colleagues formed another theory. A year or two after their experiments demonstrating the contagious nature of the disease, they realized that the placentas of sick or infected ewes could be a vehicle of contamination. Placentas expelled during parturition are eaten by other sheep, and sheep are generally kept together in a confined space during lambing. Such conditions would be perfect for spreading the disease if contamination could take place orally, which had already been demonstrated, and if the placenta contained the infectious agent, which remained to be proven. No sooner said than done— although the concept of "no sooner" has to be seen in the context of the time it took to carry out the necessary experiments. Anyway, three years later, in 1972, the theory had been substantiated: Oral inoculation of a suspension of placental membrane from a sick ewe resulted in the appearance of scrapie both in sheep and in goats. If the placenta played a major role in natural transmission, this could be another explanation for the apparent contradiction between the two series of experiments by which Pattison had tried to prove that the disease was contagious: In the first series, which had a negative result, the scrapie carriers were either males or nonpregnant females; but there were some pregnant females in the second series, in which contagion was observed.
A possible route for contamination had thus been established, but what was its real importance? And were there other possible routes? No one knew.
Pattison felt that the placental theory could even account for a strange observation made in 1954 by the Icelandic virologist Björn Sigurdsson and confirmed by others: Healthy animals could be contaminated without direct contact with sick animals, merely by frequenting places where such animals had spent time. That recalled the old "accursed" fields in which animals regularly contracted anthrax, for which Pasteur had found an explanation (see Chapter 3). In Iceland, animal husbandry had always been a major economic activity. Ovine diseases, often introduced when the animals were imported from abroad, had more than once caused famine on the island. In the early 1940s such a situation was brewing, as three new diseases were devastating the sheep population. It appeared that they had been introduced in 1934 by twenty sheep purchased in Germany.
Having returned from advanced training in Denmark and the United States, Sigurdsson tackled the new diseases. He found that one of them was caused by a previously unknown virus, later named the visna virus. To eradicate that virus, which was causing severe damage to Icelandic farmers, it was necessary to systematically destroy all flocks containing affected sheep. Some of those flocks also included animals infected with rida, the Icelandic equivalent of scrapie. A few months or a few years after such a flock was destroyed, it would be replaced with animals from areas free of rida. Without fail, the new flock would contract rida. But if animals of the same origin were used to replace a flock that had been free of rida, the disease would not appear in the new flock. It appeared as though the fields or sheepfolds had been contaminated with the rida agent, and as though this agent remained until the arrival of the new animals and then infected them.
It was Pattison's view that, in light of its great hardiness, the scrapie agent could persist in pastures or farm buildings once having been deposited there by means of contaminated placentas. Indeed, experiments by other scientists, published in 1991, confirmed that extracts from the brains of animals sick with scrapie retained a significant degree of infectiousness after having been buried in a garden for three years. Perhaps, then, animals could become infected by eating vegetation that had previously been contaminated via placentas.
A great number of animals had to be studied in experiments to confirm the infectious and contagious nature of scrapie. In the course of that work, lesions caused by the virus were studied far more closely than Charles Besnoit had been able to do in the late nineteenth century. This work involved sheep, goats, and mice alike, and it confirmed that no non—nervous system organs underwent visible change. On the other hand, nervous system lesions proved to be more extensive than Besnoit's observations had suggested. Besnoit had observed changes principally in the spinal cord and the peripheral nerves, but in fact the brain itself was the focus of large-scale degeneration of the neurons, which are the basic cells of the nervous system. In the brain, as in the spinal cord, the degeneration was characterized in particular by the presence of bubble-like vacuoles both within and between cells. Some parts of the brain resembled Swiss cheese, or a sponge.
By the early 1960s, knowledge of scrapie had expanded greatly. We knew that it was an infectious, moderately contagious disease. And, while the causative agent had yet to be identified, we knew that it had very distinctive characteristics (such as its resistance to formaldehyde) and that it could multiply in a variety of tissues, although it had a preference for nervous system tissues, where it caused characteristic lesions.
These results—obtained by a handful of mainly British and French veterinary scientists at the cost of the lives of many, many animals— were known only to other veterinary scientists and well-informed farmers, who were the audience for publications and conferences on the subject. Few physicians had even heard of the disease, and even fewer members of the lay public.
But in the course of the 1960s, the Fore people of Papua New Guinea would break down the walls surrounding knowledge of scrapie, for The Disease had struck them, this time under the name of kuru.
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