Man-made Creutzfeldt-Jakob and mad cow disease
By Lynette J. Dumble
Revelations in Britain have brought a new dimension to the incurable brain infections, Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle. Previously, science and health experts had maintained that humans could not catch CJD from eating BSE-infected beef. An announcement in the House of Commons on March 20 turned that assurance on its head with an admission that meat products from BSE-infected cattle had probably spread a novel form of CJD to humans.
Attracting less international attention, a landmark High Court ruling on July 21 deemed that the Department of Health had been negligent in permitting the human pituitary growth hormone treatment of short-statured children up until 1985, following warnings back in 1977 that the hormone was possibly contaminated with the agent of CJD.
CJD was formerly a rare disease affecting less than one person per million in most countries. Now one worst case scenario predicts that the incidence of CJD in the UK will escalate from 50 annually to claim 10,000 Britons by the year 2000, and a further 10 million by 2010. Another predicts that half the British people, some 30 million, will be left brain dead by CJD.
While a CJD epidemic of this proportion defies contemplation, it becomes increasingly obvious that the BSE/CJD tragedies were born out of a brain-dead culture that arose from overlapping agricultural and medical impropriety.
The legacy is a public health and economic scandal of unequalled proportions. Responsible management of the disastrous situation is largely dependent on overturning the brain-dead notions which have established the dire 1996 BSE/CJD position.
Faced with a worldwide boycott of British beef, and with millions of cattle destined for cremation, authorities have persisted with face-saving reassurances, the majority of which have been disproved with almost monotonous regularity.
More outrageously, modern imperialists have suggested that the Third World is the answer, and already India, Cambodia and Afghanistan have, very unofficially, been touted as dumping grounds for BSE-infected cattle in a last ditch attempt to save Britain from financial ruin. The absurd reassurances and insane answers are a fair sign that little, if anything, has been learned from 60 years of witless economics, science and politics.
Malignant twists of nature, from bubonic plague to potato blight, have killed masses throughout the ages, but the present story of spongiform encephalopathies is unique in that the epidemic was largely man-made.
Scrapie, the sheep equivalent of BSE/CJD, has been around for two centuries. Human spongiform encephalopathy was unheard of before two German physicians, Creutzfeldt and Jakob, independently reported the initial cases in the 1920s. There is no acknowledged screening test to detect BSE or CJD infection, and there is no known medication that can cure or allay the diseases.
In humans, outward symptoms emerge only after an extremely prolonged incubation period. By that stage, the agent of CJD has already turned the brain into the sponge-like mass that led this group of diseases to be classified as spongiform slow virus disorders.
The original lesson about the infectious nature of these diseases came from a 1934 vaccine catastrophe in the UK which brought scrapie to almost 5000 out of 18,000 lambs within two years of their immunisation against louping-ill virus infection. Scientists discovered that the vaccine serum was prepared from lambs whose dams had subsequently developed scrapie or "mad sheep disease".
The significance of scrapie passing vertically from ewes to their lambs, and horizontally from lamb to lamb via vaccine injections, was kept from international eyes when egotistical carrying-on prevented the data from reaching the pages of the scientific literature for a further 15 years.
"Mad sheep disease" jumped the species barrier when a scrapie-infected food supplement brought a similar brain illness to farm mink in 1947. This news scarcely interested the medico-scientific community, which had become intensely preoccupied with another incurable brain illness, kuru, which had reached epidemic proportions amongst the Fore people in the highlands of New Guinea.
Anthropologists traced kuru back to the reverent consumption of deceased tribal members' bodies, with the brain almost certainly being the infectious denominator. Kuru was essentially eradicated when New Guinea authorities in 1959 outlawed the eating of human flesh. The 1976 Nobel Prize was awarded to Carlton Gajdusek, whose experiments had demonstrated that injections of kuru brain in 1967, and CJD brain in 1969, reproduced similar illnesses in chimpanzees. Gajdusek's research put an end to ideas that species barriers were an impediment to the spread of this type of disease.
Two neuroscientists from Yale University, Laura and the late Eli Manuelides, went on to illustrate by 1975 that injections of human blood, like injections of brain taken from kuru and CJD victims, transmitted the disease across the species barrier to laboratory animals. Their unheeded message implied that blood was the vehicle that carried the agent of CJD around the body until it chanced upon a hospitable residence like the brain.
This meant that recipients exposed to human pituitary gland hormone injections, or to blood or organ transplants from a donor with CJD, risked becoming secondary CJD hosts.
Even as the understanding of spongiform encephalopathy increased, human pituitary hormone programs in various countries were attracting hefty government sponsorships. Few of the programs' stalwarts caught on to the implications of the Manuelides' experiments, a notable exception being British scientist Alan Dickinson, a scrapie expert, who between 1978 and 1982 unsuccessfully attempted to filter the CJD agent out of the pituitary hormones being injected into unsuspecting short-statured children and infertile women.
A British Royal Commission on Environmental Pollution in 1979 raised the possibility that the unregulated cycling of protein-rich sheep remains back into animal feed might spread scrapie to cattle, as it had done to farm mink three decades beforehand.
At the same time, the push to retrieve more and more human pituitary glands for growth hormone production reached into India. Millions of pituitaries were harvested from cadavers in the subcontinent and sent to government laboratories in Europe and North America. The promised repayment in kind, namely a supply of extracted growth hormone to treat short-statured children in India, was broken. Ironically, that broken imperialist promise may account for India's enviable present position of absence of CJD.
By 1985, the first of the fatal legacies from the medical complacency emerged with four cases of CJD in human pituitary growth hormone-treated children. Programs were immediately halted in most countries, the notable exception being France, where the treatment of children continued, based on the haughty assumption that the purity of the French hormone-extraction process accounted for the absence of CJD to that point. Four years later, during which time the number of French children at risk of growth-hormone-related CJD had doubled, the first French children fulfilled that tragic legacy; by 1996, France had half of the world's 90 cases of pituitary hormone-related CJD.
A wall of invisibility has been built around the women victims of the human pituitary hormone programs. Unlike growth hormone-treated children, whose years of injections made it impossible for paediatricians to avoid the clerical red tape that came with government sponsorship, women's gonadotrophin injections usually lasted for less than six months. As a result, there was frequently left-over hormone that infertility specialists could inject into new candidates without going through the bureaucratic application process for further supplies, and government records of women exposed to pituitary gonadotrophin were far from complete.
Additionally, in 1988 the National Institutes of Health in the United States concluded that the short-term nature of the gonadotrophin treatment precluded any risk of contracting CJD, and shredded the records of infertile women treated by some 250 US gynaecologists over the previous 15 years. A year later, the pituitary infertility hormone, gonadotrophin, snared its first CJD victim, a 40-year-old woman in Australia. By 1993, the CJD of another three Australian women, all aged within a year or two of 40, had been traced back to injections of pituitary gonadotrophin.
By the time news of pituitary gonadotrophin-related CJD hit the headlines in Britain in 1993, authorities were unable to answer inquiries, including one that came from a 32-year-old woman whose mother had died of CJD in 1975 after receiving five pituitary gonadotrophin injections in 1960, because whatever records had once existed had by then also been shredded.
Officially, 300 infertile British women were exposed to pituitary gonadotrophin, but medical literature from UK infertility circles, dating back to the 1960s, indicates that the number was probably much larger. While the risk of gonadotrophin-related CJD to Australian and British women has been highly publicised, the entire issue for American, German and Scandinavian women has barely been touched.
Third World children and women did not escape the insanity of human pituitary hormone programs. A medical report in 1991 linked the CJD death of a young Brazilian man, like those of five youthful New Zealand men and women, with a childhood treatment involving pituitary growth hormone obtained from the US. The fate of women in Mexico City whose breasts were injected with US pituitary hormones, in an appalling experiment to increase the volume of milk in lactating mothers, some already pregnant again, will never be known.
The opportunity to contain the CJD legacy of pituitary gonadotrophin injections has probably been lost as women unwittingly risk spreading their legacy via blood donation. Similarly, the possibility that women treated with pituitary gonadotrophin may have transmitted their CJD legacy to their children has been totally cast aside, and there is an overwhelming medical disinterest in investigating whether pituitary hormone treatments in the 1960s, 1970s and 1980s may account for the CJD deaths of women, aged a decade younger than the average age of sporadic CJD victims, which litter the pages of medical journals in the 1990s.
Oddly, although the concept of blood-transfusion-related CJD was dismissed by health authorities, by 1987 all US and New Zealand registered recipients of pituitary growth hormone had been advised not to donate blood or organs. It took until 1992 for Australian and British blood banks and transplant programs to follow suit, so the Australian and UK general communities were exposed to the risk of secondary CJD transmission for five years longer than their US and New Zealand counterparts.
Oddly too, although the theory of blood-transmitted CJD remained largely unproven in humans, actions in the past two years indicate that authorities have opened their minds to the public health consequences of the Manuelides' experiments.
Canadian authorities spent $18 million in 1995 to withdraw pooled plasma, already in the process of being transfused to thousands, on the grounds that it contained a donation from a man who had subsequently died of CJD. In 1996, New Zealand authorities bit the bullet, albeit under public pressure, to quarantine blood products that had been contaminated by a donation from a CJD-infected donor. British blood banks also increased their precautionary measures with an extended questioning routine designed to screen out relatives of CJD victims.
British microbiologist Stephen Dealler estimates CJD-infected blood may reach as many as 60,000 recipients each year, but the years-long incubation time increases the difficulty of linking a blood recipient's CJD with a donor source. It falls within the realms of possibility that secondary CJD in a transfusion recipient may appear years before the primary CJD in a blood donor.
One year after the first cases of pituitary growth hormone-related CJD in 1985, the first of the protein-fed cattle came down with BSE. Advisory committees were set up around the world. Apparently none had the foresight to include public health experts trained to weigh policy in terms of both best- and worst-case predictions.
Instead, for the next 10 years authorities seized every chance to preserve the reputations and careers of eminent politicians, physicians and scientists, and managed to allay public anxiety by keeping news of their bungles out of the media. Public and animal health ran a very poor second to the market interests that had transformed cattle from BSE-free herbivores into BSE-infected carnivores. Even as BSE emerged in protein-fed British cattle in 1986, scientific advice that the epidemic could best be contained by the immediate destruction of the 10,000-odd infected cattle was dismissed solely on the basis of the financial cost.
Following the ban on scrapie-contaminated animal feed in 1988, BSE in cattle was supposed to be under control. According to authorities, the peak 1992 weekly average of 700 new cases of BSE has fallen to 70 cases per week in 1996. At the same time, the notion of control was practically contradicted by the BSE in some 27,000 cattle born after the 1988 ban. These figures, together with the 60% of 1996 cases occurring in cattle born post-1988, indicated that cattle had passed BSE on to their calves. Earlier suggestions that the BSE epidemic in cattle was maintained by maternal transmission had been dismissed, and at times ridiculed, until a 1996 study proved otherwise.
Erring on the side of caution has fallen foul of the brain-dead culture underpinning the BSE/CJD fiasco. As an example, the British Ministry of Agriculture, Fisheries and Food (MAFF) sabotaged a 1990 Brussels ruling designed to prevent the spread of BSE to the European mainland. MAFF issued civil servants with secret orders to skip the computer vetting of calves set for the lucrative saleyards of the European Union. As a result, there were no checks to determine whether about 2 million veal calves sold to the EU between 1990 and 1995 were born to BSE-infected cows or not.
Even the computer tracing of the BSE parentage of some 2000 cattle sold for foreign breeding after 1990 may be untrustworthy, partly because of MAFF's skulduggery and partly because the mean incubation period of BSE is five years.
An estimated 700,000 BSE-infected cattle entered the human food chain, chiefly because the animals' slaughter age, usually three years, predated the age at which they would show signs of BSE infection. For the same reason, there is no way of knowing the number of breeding stock that were exported before their sire or dam's BSE was subsequently discovered.
Britain was not alone in the cover-up. In September 1996, the French newspaper Libération revealed that a memorandum from French official Gilbert Castille had suggested back in 1990 that Britain ought to be asked not to publish its research results, saying "it would be better to minimise BSE by practising disinformation". Brussels â via Guy Legras, head of the European Commission's agricultural directorate â warned of the financial repercussions from a beef panic and hushed up news of the BSE situation.
Cattle may not be the only species within the meat industry that are harbouring the BSE/CJD agent. Until March 1996, no restrictions were placed on feeding cattle offal to pigs and hens. Together with a common practice whereby animal-feed manufacturers use the same equipment to mix both cattle and pig-feed, this approach reflects a glaring ignorance about the highly infectious nature of diseases such as BSE and CJD.
This background, together with the extreme resistance of BSE and CJD to high temperatures and caustic chemicals, may explain the disproportional share of CJD infection occurring in the farming community. It also brings the focus back to blood-transmitted CJD, and raises the prospect of simple kitchen injuries introducing BSE from meat products into the bloodstream of an unsuspecting public.
Some argue that the BSE panic is thinly supported by firm scientific evidence. Insults fly back and forth about mad cows and mad politicians. History will be the ultimate judge, but in the absence of a plausible alternative to BSE-infected beef that would account for the recent spate of unconventional CJD in youthful victims, both animals and humans deserve a policy that errs on the side of caution.
Medical impropriety has already destroyed the lives of 90 pituitary hormone recipients and their families; young lives have been snuffed out by an atypical, but equally cruel, form of CJD that appears to have come from herds infected by agricultural impropriety; and British cattle are at threat of extinction because of BSE inflicted on them during a period of financial megalomania.
Sixty years of underestimating the gravity of CJD/BSE issues for both humans and animals is enough. Notions that culling half of Britain's cattle population could make early inroads into global greenhouse targets, like those that propose restocking the sacred herds of India, or detonating Cambodia's and Afghanistan's land mines with BSE-infected cattle, are barbarous extensions of a brain-dead culture which told the public that "there is no evidence" of serious danger. More truthfully, there was "no way of telling", and it remains to be seen whether the final consequences will match those of the AIDS epidemic.
A worst case CJD epidemic will smash rather than stretch every available human resource. Imperialists have widened the gap between developed and developing regions with modern discrimination that transgresses the boundaries of animal and human rights, development, environment, nuclear weapons, population, trade and wealth. Wary of its use as a virtual dumping ground for nuclear waste, toxic chemicals and perilous medications, the Third World will not be caught out by the proposals of brain-dead imperialists to become a storage yard for manmade BSE. [Dr Lynette J. Dumble is senior research fellow, University of Melbourne's Department of Surgery, Royal Melbourne Hospital.]