And goats AND mice

By then scrapie had turned up in Canada, the United States, and Australia in the wake of importation of sheep from the United Kingdom. Those countries, along with New Zealand, imposed an embargo on such sheep unless they could be guaranteed scrapie-free. Now, finding the source of the disease became an economic issue. Motivated and well financed, British veterinarians resumed large-scale experimentation at two major research centers the Agricultural Research...

Where Does The Bse Epidemic Stand

In the United Kingdom, the BSE epidemic continues its decline. In 2001, the number of new cases was around fifty per month, whereas it had been double that figure in 2000. That decline may not be as speedy as one might have hoped, but that is surely due in part to ever more active monitoring. The thorniest point is that a small number of the cases declared in 2001 were in cattle born after 1996, the year that saw the adoption of the strictest prohibitions on feeding MBMs to farm animals,...

Epilogue

By possessing many characteristics that run completely counter to orthodox scientific thinking, it has long managed to evade the pursuit mounted by veterinarians, physicians, and researchers. The Disease is transmissible, but its incubation period is far longer than anything ever seen before. It is infectious, but it triggers no defensive reaction in the body a strange characteristic that for years led researchers down the garden path. It is caused by an...

The wall comes down

NOT THE BERLIN WALL this was 1959, and that structure would not rise for another two years but the wall that segregated physicians and veterinarians was toppling. That year saw the first suggestion of a similarity between a human form of The Disease kuru and its animal form, scrapie. Let us return to the Compton research center in England, where Iain Pattison and his colleagues were at work. When the issue of scrapie in sheep that were exported to the United States arose, an American veterinary...

The Human Toll

What is the state of affairs with new variant Creutzfeldt-Jakob disease, which is almost certainly the result of the transmission of the BSE agent to humans By the end of 2000 a total of eighty-six people had died of it eighty-two in the United Kingdom, three in France, and one in Ireland. A year later the total was 101, meaning that there had been fifteen deaths from new variant CJD in 2001, about the same number as in 1998 (eighteen) and 1999 (fifteen), but far less than in 2000 (thirty). The...

April 1985

It seemed as though The Disease had been flushed out. But it counterattacked on two fronts, launching deadly offensives whose effects would still be felt fifteen years later. As described in Chapter 15, Prusiner believed that The Disease was caused by a kind of protein, which he named a prion. It is not hard to imagine a toxic protein, for there are many precedents. The toxins produced by the bacteria that cause diphtheria, anthrax, and botulism are proteins, and...

Treatment And Prevention

For years, Stanley Prusiner's laboratory has been searching for molecules that could serve as drugs to treat prion diseases. In August 2001 it announced some apparently promising results.4 Researchers there had focused on molecules that could reach the brain those able to cross the blood-brain barrier. Among these, drugs long used to treat malaria, such as quinacrine, proved to cause a rapid decrease in the quantity of prion in cultures of infected cells. Nothing we now know can explain this...

The kiss of death

LET US LEAVE THE DOCTORS and veterinarians to their confusion and concern, and return for a moment to the guilty party the causative agent of The Disease, the prion. As we have seen, this appeared to be a protein encoded by a gene that was present, with very similar sequences, in all mammals. Normally, this gene would encode a protein containing 240 amino acids that, like most other proteins, was protease-sensitive. But in animals with scrapie or humans with Creutzfeldt-Jakob disease, the...

Notes

Mathieu, Quelques mots sur la question ovine. Vente de b liers Grignon, Recueil de M decine V t rinaire 53 (1876) 804 808. 2. T. Comber, Real Improvements in Agriculture (on the Principles of A. Young, Esq.). Letters to Reade Peacock, Esq., and to Dr Hunter, Physician in York, Concerning the Rickets in Sheep (London Nicholl, 1772), 73 83. 3. Journal of the House of Commons 27 (1755) 87. See also T. Davis, General View of the Agriculture of Wiltshire (London Phillips, 1811), 145 146. 4. I....

Have we conquered the disease

IN NOVEMBER 2000 a French television network broadcast a program titled Mad Cow Running Scared. The Disease which had been lurking in the days of Louis XV and which we've been hunting down for the past three centuries is still spreading fear today. Even if we have unmasked it, we have not conquered it. The public has been deeply shocked by images of young people, of mothers, unable to move about, speak, or even show any sign that they understand what is said to them, incontinent and awaiting a...

Info

AS THE FRENCH EDITION of this book went to press toward the end of 2000, Europe's mad cow crisis was at its height. A year later, the crisis was still with us but seemed less intense. Beef consumption had picked up somewhat in France, but concerns about lamb and mutton emerged. In countries that had been BSE-free, the first cases of the disease triggered panics like those that had been experienced in the United Kingdom and then in France. In the scientific arena, many and often extremely...

Prions

DESPITE THE AVALANCHE OF THEORIES loosed by the observations of Alper and her colleagues, nothing spectacular was published during the 1970s about the nature of the mysterious virus that was seemingly without nucleic acid. Enter a man who continues to occupy center stage to this day Stanley Prusiner, a neurologist and biochemist who since 1974 has divided his time between the San Francisco and Berkeley campuses of the University of California. Starting in 1978, but primarily in the early 1980s,...

From cows to humans

THE POSSIBILITY THAT BSE could be transmitted to humans was considered as soon as the disease became known. In June 1988 the question was posed in a British Medical Journal editorial We are faced with the fact that spongiform encephalopathy, whether or not we are at risk from it ourselves, is now established in the cattle of this country. . . . There is no way of telling which cattle are infected until features develop, and if transmission has already occurred to man it might be years before...

One case per million

AS A RARE, POSSIBLY GENETIC AILMENT, Creutzfeldt-Jakob disease was of interest to only a handful of doctors and researchers between 1920 and 1960. But there had been enough interest to ensure the gathering of data on patients who had been treated in several countries. During the 1960s, the question of whether CJD was a single disease became a matter of increasing controversy. Citing the diversity of clinical symptoms and of the lesions observed in nervous system tissues, some were convinced...

The phantom virus

IN FEBRUARY 1966 Gajdusek published his findings on the transmission of kuru to chimpanzees. As William Hadlow had predicted (see Chapter 10), kuru thus proved to be similar to scrapie. The same month saw the publication of an article that would puzzle the scientific community. We will address that in a moment, but first What was known at that point about the virus or viruses responsible for these diseases Let us focus on the one that causes scrapie, about which more complete information was...

Molecules and microbes

PASTEUR'S EARLY WORK related to what we now call physical chemistry. Before Pasteur, chemists had established that substances solids, liquids, and gases alike were in general composed of molecules, which were in turn composed of atoms. A so-called pure substance contains molecules of a single kind, each containing a particular number of atoms linked by very specific bonds. As Antoine Lavoisier (1743 1794) demonstrated in his work during 1783 1785, for example, a molecule of water consists of...

The secret in the closet

WE HAVE BEEN ON THE TRAIL of The Disease for three centuries now. If it has managed to evade capture for so long, this is due in large part to its disturbing ability to alter its appearance. The closet in which this criminal stores its disguises seems to be infinitely deep. So what is its secret Can prion theory help us figure it out From the very outset we knew that The Disease could change its appearance. Think of how hard it was to realize that scrapie in all its forms was in fact a single...

Lessons learned

COULD THE TRAGEDY have been averted In theory, perhaps, but only at the cost of abandoning the treatment of pituitary dwarfism. By the late 1960s even before the foundation of L'Association France Hypophyse the scientific literature contained information that could have signaled the danger of administering growth hormone derived from human pituitaries. But pediatricians and endocrinologists treating pituitary dwarfism either did not know of that information or did not fully appreciate it....

How The Cows Turned

The publisher gratefully acknowledges the generous contribution to this book provided by the French Ministry of Culture. Comment les vaches sont devenues folles, by Maxime Schwartz, is published in English translation by arrangement with ditions Odile Jacob, ditions Odile Jacob, Mars 2001. University of California Press Berkeley and Los Angeles, California University of California Press, Ltd. London, England 2003 The Regents of the University of California Library of Congress...

From cows to sheep from humans to humans

AS THOUGH FEARS ABOUT EATING BEEF and other cattle products were not enough, some people began to worry about the possible risks of eating products from other animals first and foremost sheep. The fact is that cows were not the only animals to have been given potentially contaminated animal-based feeds these had been fed also to sheep, hogs, chickens, and even fish. Could it not be risky to eat meat or other products from those animals as well especially since, for some of them, animal-based...

Unmasking the disease

SO, THE DISEASE APPEARS to be caused by a molecule, a protein that is more or less the same in all species that fall victim to it. Does this hypothesis in its present form account for all the various characteristics of The Disease Before saying that it does, we should look at a few more questions. One obvious question, which we addressed earlier, relates to the precise nature of the changes in conformation that turn the prion protein infectious. The conformation of the normal protein has been...

Diagnosis Of Transmissible Spongiform Encephalopathies Tses

One particularly active area of research was diagnosis. Traditional tests were able to detect the prion in tissue sections or brain extracts. They relied on antibodies that could recognize the prion protein in both its normal and pathogenic forms the two could be distinguished because the normal form was destroyed by proteases under conditions when the pathogenic form was not. These tests have two main limitations Their sensitivity is limited, and they can be carried out only after death. Re...

How Did The Cows Go

Let us now return to the question that this book was supposed to answer How did the cows go mad More precisely, did this disease come about as assumed at the beginning of the BSE epidemic because cattle were fed meat and bone meal containing the causative agent of scrapie The debate (of which I spoke in Chapter 21) is far from over. Why was an epizootic an animal epidemic declared at one particular time, the early 1980s, and only in the United Kingdom Using animal-based meals to feed cattle is...

The return of the spontaneists

We have known this since the 1936 experiments of Cuille and Chelle and the accidental contamination of thousands of sheep in Scotland by a louping ill vaccine around the same time. Human spongiform encephalopathies kuru and Creutzfeldt-Jakob disease are infectious as well, as Gajdusek's team demonstrated in the late 1960s by transmitting them to chimpanzees. So if you accept the orthodox Pasteurian contagionist view, these diseases can be contracted only through...

Have the cows gone mad

ALTHOUGH THE FIRST CASES of bovine spongiform encephalopathy were recorded in April 1985, they were not identified as such until two years later. That may seem surprising, but we must recall that a single cow in a herd dying, even of a murky cause, is not so extraordinary as to justify an in-depth investigation. The animal is written off as a loss on the balance sheet, its carcass is sent to the processing plant, and nothing more is said of it. Things become more serious when there are several...

To growand to die

AND DIE That was the sad fate of at least 140 children treated with human growth hormone and infected with the causative agent of Creutzfeldt-Jakob disease. The final outcome of this tragedy remains to be known owing to the lengthy incubation period of CJD, additional cases appear every year. The announcement of the first cases, in April 1985, took specialists by surprise the vast majority of them had not seriously contemplated the possibility of such infection. Although in the...

Chronology

DATE THE HUNT THE SCIENCE THE DISEASE'S COUNTERATTACKS Earliest known descriptions of scrapie are recorded. Pasteur invents three-dimensional chemistry. Mendel discovers what were later called genes. Pasteur and Koch demonstrate the role of microbes in contagious disease. Besnoit discovers the presence of vacuoles in the neurons of sheep with scrapie. Science begins to address genetics and the chromosome theory of heredity. Scrapie appears to be contagious in natural conditions. Creutzfeldt and...

A tragedy in the making

HERE IS WHERE THE HUNT for The Disease stood in 1959 British veterinary researchers had transmitted scrapie to goats, but not yet to mice. The writings of Creutzfeldt and Jakob were gathering dust on library shelves. Gajdusek had left the Fore people and had learned of Hadlow's theory positing a parallel between scrapie and kuru. The year 1959 also saw the early triumphs of molecular biology. Watson and Crick had published their historic article six years before, and Jacob and Monod would...

Have Sheep Been Contaminated

There was much talk of sheep in 2001. At least two questions were being asked. The first and most urgent was whether they could have been contaminated by the BSE agent and whether sheep products could thus be capable of transmitting BSE to humans. The second, not entirely unrelated, question was whether the BSE epidemic could have started with the transmission of scrapie to cattle through the consumption of meat and bone meal (MBM). In Chapter 23 we discussed the possibility that the BSE agent...

Acknowledgments

First of all, I apologize to all the many colleagues to whose work I have referred without attribution. By citing relatively few names, I sought to avoid weighing down the text with an excessively scholarly appearance. My wife Brigitte strongly encouraged me to write this book, and was a constant source of support throughout the project. My many conversations with her, and with our daughter Barbara, were invaluable. One colleague and very good friend, who played a major role in my decision to...

Creutzfeldt jakob and others

THE POSTHUMOUS LEGACY of Hans Gerhard Creutzfeldt is a strange one. He died in 1964 virtually unknown, but two decades later his name was to be world famous although some today question whether his renown is really justified. In any event, that fame is due to an obscure paper published in 1920 in a German neurological-psychological journal. Creutzfeldt was an exceptional human being an original, independent thinker, and a man whose brusque manner concealed great kindness and profound humility....

The sheep are strangely dizzy

THE EIGHTEENTH CENTURY, which was to conclude with the American and French Revolutions, was also the Age of Enlightenment. The conviction was growing that scientific progress was intended to enable humans to control the world around us Had we not learned to control thunderbolts, thanks to the lightning rod This was the era of Linnaeus, Buffon, and Diderot, and we began cataloguing nature's riches and seeking to employ them in a more rational way. This approach was seen particularly in the areas...

Mad dogs and earthworms

PASTEUR AND KOCH had established that anthrax was caused by a bacterium, but how was it transmitted within a flock That would also be the question a century later for scrapie and BSE. In some flocks, anthrax is endemic from time to time, an animal will succumb to it. In other flocks, it affects a large number of animals within a short space of time, thus becoming epidemic. Furthermore, it can flare up periodically or remain dormant for many years. Koch reported two important facts that advanced...

Scrapie is contagious

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...

Scrapie is inoculable

ON DECEMBER 28, 1936, the French veterinarians Jean Cuill and PaulLouis Chelle presented to the Acad mie des Sciences a communication titled Is the Disease Known as Scrapie Inoculable They reported having used a variety of techniques to inoculate nine sheep of both sexes with cerebral or medullar matter from a number of animals in the latter stages of scrapie. In the course of the nine months following the inoculation, seven died or were sacrificed for reasons beyond the control of the...

Scrapie under the microscope

IN 1898, THREE YEARS AFTER Pasteur's death, Professor Charles Besnoit of the cole V t rinaire d'Alfort learned that for several years an unknown disease had been ravaging flocks in the Tarn, in southwest France. Mortality had reached 15 to 20 percent, devastating for a region where sheep were important not only for wool and meat, but also for milk used in cheese production. Besnoit soon realized that this unknown disease was scrapie, and he decided to study it becoming the first to do so in a...

From pearl necklace to double helix

In Paris, the United States, and throughout the developed world, students were taking to the streets to protest war, intolerance, and other social ills. How was the hunt for The Disease going A composite sketch was emerging In very similar guises, it attacked sheep and goats as scrapie it affected the Fore people of Papua New Guinea as kuru and it threatened the rest of the human world as Creutzfeldt-Jakob disease. It could be transmitted experimentally both within a...

Kuru and the fore people of papua new guinea

SOME PLANTS AND ANIMALS ARE so-called living fossils. They seem to have survived since time immemorial while their contemporaries fell by the wayside, yielding to new species better adapted to a changing world. As of the mid-twentieth century, the human species too included its share of well-adapted survivors groups cut off from the rest of the world, who lived as our distant ancestors had lived. Among them were a number of ethnic groups on a huge island to the north of Australia, which had...