of inherited diseases, and contagious diseases in which inheritance determines susceptibility — cholera being a now classic case —
but the notion that an infectious particle could somehow travel through the germline seemed to break all the rules of biology. The scientist, James Parry, was firmly put in his place.
About this time an American scientist, Bill Hadlow saw pictures of the damaged brains of scrapie-riddled sheep in an exhibit in the Wellcome Museum of Medicine in London. He was struck by their similarity to pictures he had seen from a very different place. Scrapie was about to get a lot more relevant to people. The place was Papua New Guinea, where a terrible debilitating disease of the brain, known as kuru, had been striking down large numbers of people, especially women, in one tribe known as the Fore. First, their legs began to wobble, then their whole bodies started to shake, their speech became slurred and they burst into unexpected laughter. Within a year, as the brain progressively dissolved from within, the victim would be dead. By the late 1950s, kuru was the leading cause of death among Fore women, and it had killed so many that men outnumbered women by three to one. Children also caught the disease, but comparatively few adult men.
This proved a crucial clue. In 1957 Vincent Zigas and Carleton Gajdusek, two western doctors working in the area, soon realised what had been happening. When somebody died, the body was ceremonially dismembered by the women of the tribe as part of the funeral ritual and, according to anecdote, eaten. Funereal cannibalism was well on the way to being stamped out by the government, and it had acquired sufficient stigma that few people were prepared to talk openly about it. This has led some to question whether it ever happened. But Gajdusek and others gathered sufficient eye-witness accounts to leave little doubt that the Fore were not lying when 2 7 4 G E N O M E
they described pre-1960 funeral rituals in Pidgin as 'katim na kukim na kaikai' - or cut up, cook and eat. Generally, the women and children ate the organs and brains; the men ate the muscle. This immediately suggested an explanation for kuru's pattern of appearance. It was commonest among women and children; it appeared among relatives of victims - but among married relations as well as blood relatives; and after cannibalism became illegal, the age of its victims steadily increased. In particular, Robert Klitzman, a student of Gajdusek's, identified three clusters of deaths, each of which included only those who attended certain funerals of kuru victims in the 1940s and 1950s. For instance, at the funeral of a woman called Neno in 1954, twelve of fifteen relatives who attended later died of kuru. The three who did not comprised somebody who died young of another cause, somebody who was forbidden by tradition to take part in the eating because she was married to the same man as the dead woman, and somebody who later claimed to have eaten only a hand.
When Bill Hadlow saw the similarity between kuru-riddled human brains and scrapie-riddled sheep brains, he immediately wrote to Gajdusek in New Guinea. Gajdusek followed up the hint. If kuru was a form of scrapie, then it should be possible to transmit it from people to animals by direct injection into the brain. In 1962 his colleague, Joe Gibbs, began a long series of experiments to try to infect chimpanzees and monkeys with kuru from the brains of dead Fore people (whether such an experiment would now be regarded as ethical is outside the scope of this book). The first two chimpanzees sickened and died within two years of the injections. Their symptoms were like those of kuru victims.
Proving that kuru was a natural human form of scrapie did not help much, since scrapie studies were in such confusion over what could be the cause. Ever since 1900, a rare and fatal human brain disease had been teasing neurologists. The first case of what came to be known as Creutzfeldt-Jakob disease, or C J D , was diagnosed by Hans Creutzfeldt in Breslau in that year in an eleven-year-old girl who died slowly over the succeeding decade. Since C J D almost never strikes the very young and rarely takes so long to kill, this P O L I T I C S 2 7 5
was almost certainly a strange case of misdiagnosis at the outset leaving us with a paradox all too typical of this mysterious disease: the first C J D patient ever recognised did not have C J D . However, in the 1920s, Alfons Jakob did find cases of what probably was C J D and the name stuck.
Gibbs's chimpanzees and monkeys soon proved just as susceptible to C J D as they had been
patient, but they had been properly sterilised after use. Not only did the mysterious entity that caused the disease resist formalin, detergent, boiling and irradiation, it survived surgical sterilisation. The electrodes were flown to Bethesda to be used on chimps, who promptly got C J D , too. This proved the beginning of a new and yet more bizarre epidemic: iatrogenic ('doctor-caused') C J D . It has since killed nearly one hundred people who had been treated for small stature with human growth hormone prepared from the pituitary glands of cadavers. Because several thousand pituitaries contributed to each recipient of the hormone, the process amplified the very few natural cases of C J D into a real epidemic. But if you condemn science for a Faustian meddling with nature that backfired, give it the credit for solving this problem, too. Even before the extent of the growth-hormone C J D epidemic had been recognised in 1984, synthetic growth hormone, one of the first products to come from genetically engineered bacteria, was replacing the cadaver-derived hormone.
Let us take stock of this strange tale as it appeared in about 1980.
Sheep, mink, monkeys, mice and people could all acquire versions of the same disease by the injection of contaminated brain. The contamination survived almost all normal germ-killing procedures and remained wholly invisible to even the most powerful electron microscopes. Yet it was not contagious in everyday life, did not seem to pass through mother's milk, raised no immune response, stayed latent for sometimes more than twenty or thirty years and 2 7 6 G E N O M E
could be caught from tiny doses - though the likelihood of contracting the disease depended strongly on the size of the dose received. What could it be?
Almost forgotten in the excitement was the case of the Suffolk sheep and the hint that inbreeding had exacerbated scrapie at the outset. It was also gradually becoming clear that in a few human cases — though fewer than six per cent - there seemed to be a family connection that hinted at a genetic disease. The key to understanding scrapie lay not in the arsenal of the pathologist, but in that of the geneticist. Scrapie was in the genes. Nowhere was this more starkly underlined than in Israel. When Israeli scientists sought out C J D
in their own country in the mid-1970s, they noticed a remarkable thing. Fully fourteen of the cases, or thirty times more than expected by chance, were among the small number of Jews who had immigrated to Israel from Libya. Immediate suspicion fell upon their diet, which included a special predilection for sheep's brains. But no. The true explanation was genetic: all affected people were part of a single dispersed pedigree. They are now known to share a single mutation, one that is also found in a few families of Slovakians, Chileans and German- Americans.
The world of scrapie is eery and exotic yet also vaguely familiar.
At the same time that one group of scientists were being irresistably drawn to the conclusion that scrapie was in the genes, another had been entertaining a revolutionary, indeed heretical, idea that seemed at first to be heading in a contradictory direction. As early as 1967
