There was a long night ahead. A group of scientists, each expert in the minutiae of disease, had been summoned to an emergency meeting in London. Some caught planes and trains back from a conference on the European continent to be there, others dropped their routine work at some of the finest institutes in the country. What had begun as a farming problem was about to erupt into a far-reaching crisis.
At 10 the following morning, having worked through the night, those assembled released a note to the prime minister outlining what many had long been sure of. That in direct contradiction of the government's 10-year campaign of reassurance, an infection that had caused rapid and fatal brain disease in nearly 200,000 cattle posed a grave threat to human health. Ten young people had been identified as suffering from what was to become known as variant Creutzfeldt-Jakob disease (vCJD), a deadly, human form of bovine spongiform encephalopathy (BSE). Some, it became clear, had already succumbed.
The announcement of the news, on March 20 1996, fell to Tory health secretary Stephen Dorrell and caused more than a slashing of beef prices at supermarkets. Many were furious about the Conservative government's handling of the dangers of eating BSE-contaminated meat. They had heard the chief medical officer, Sir Donald Acheson, declare categorically that beef was safe for everyone to eat, a message repeated by his successor. They had seen John Gummer, then agriculture minister, feed his four-year-old daughter, Cordelia, a beefburger in front of cameras in Ipswich. Confidence in the government, and to a lesser extent the scientists it consulted, evaporated.
In the absence of hard facts, speculation over the eventual human death toll reached apocalyptic proportions. The doom-laden predictions now look to be well off the mark, but has the threat really passed? More than 10 years since Dorrell's announcement, and 20 years since the first cases of BSE were identified, at least 160 people have died from vCJD and more are expected to die soon. But despite billions spent on efforts to save Britain's beef industry and protect its citizens, all the major questions remain unanswered. The origin of the disease? A mystery. The number of people infected with vCJD? A mystery. The risk that those harbouring the disease will infect others? Again, a mystery. And since there is still no blood test and no cure, the final death toll is anyone's guess. Right now, the only sure-fire test for the disease involves examining chunks of people's brains or other internal organs, and so is usually only performed on the dead.
The story of BSE in Britain is a case study in the ruthless efficiency of intensive farming, the self-serving behaviour of government departments and the patronising caution extended to the public when explaining risk. It reveals the impotence of the scientists involved - at least at the outset, when they were being called upon to give meaningful advice while still battling to understand a disease they had never encountered before.
At the end of 1986, pathologists at the Central Veterinary Laboratory were analysing slivers of brain tissue sliced from cattle that appeared to have contracted a new disease. It left the cattle uncoordinated and jerky, and ultimately proved fatal. Under a microscope, the brain damage resembled scrapie, a disease caused by rogue proteins known as "prions" that had been endemic in the national sheep flock for nearly 200 years.
Without publicity, an investigation was launched to find the cause of the outbreak. It revealed an alarmingly widespread disease. One year later, 95 cases of BSE had been confirmed on 80 farms. By February 1988, 264 cases had been tracked back to 223 farms. The number of cases began to grow exponentially.
"It was turning into a major crisis and there was all sorts of wild guesswork going on because no one understood it," says Chris Higgins, who now chairs the government's advisory committee on spongiform encephalopathy diseases. "The politicians didn't know what to do and the scientists didn't know what to do. We didn't know where it came from, what caused it, how bad it might be. We didn't know anything."
John Wilesmith, an epidemiologist and lead investigator at the Central Veterinary Laboratory, suspected that cattle feed - the common factor linking the cases - was to blame. Specifically, he proposed that scrapie-infected sheep offal had been mixed into meat-and-bone meal, a nutritious food source that is made by grinding down and baking a slurry of sheep and cow remains. The process had been perfected by the rendering industry (which uses every scrap of the animal carcass for various products) during an efficiency drive in the aftermath of the second world war.
The investigation led to the government imposing what the cattle industry regarded, at the time, as a draconian measure - a ban on the use of certain meat-and-bone meal in feed for cattle and sheep. The ban was followed by compulsory orders to slaughter all animals showing signs of BSE. The moves were made to protect cattle, but the possibility of risk to the public had not gone unnoticed.
As events gathered pace, Acheson, the chief medical officer, set up a working party, headed by Sir Richard Southwood, an Oxford University zoologist, to advise on the implications of BSE. When the working party reported back in early 1989, it agreed that scrapie-contaminated meat and bone meal was the most likely cause of the BSE outbreak. It advised that baby-food manufacturers should stop using cow and sheep offal, especially the thymus (a gland known to be highly infected by scrapie prions), in their meat-based meals. But it still maintained that it was "most unlikely BSE would have any implications for human health".
Officials at what was then the Ministry of Agriculture, Fisheries and Food (Maff) were unsettled. If potentially infected offal from cows was not considered safe for babies, why should it be safe for adults? After wrangling with the Department of Health, a blanket ban on cow offal entering the food chain was introduced, but not before health secretary Kenneth Clarke's officials recommended he let Maff take sole responsibility for the move. They feared that the ban was going beyond the scientific advice of the Southwood committee, which maintained there was little cause for alarm.
On farms around Britain, veterinary inspectors were stretched to breaking point. Some were visiting four farms a day, making diagnoses, completing paperwork and arranging the slaughter and destruction of animals. The carcasses mounted up. Government had made the decision to leave the building of new incinerators to the private sector and many were held up by difficulties with planning permission. The carcasses that could not be incinerated were dumped in landfills.
At the Central Veterinary Laboratory and other sites, where cattle heads were being sent for brain-tissue analysis, scientists faced a growing backlog, despite working around the clock. Cases of BSE continued to rise, and by the end of 1989, nearly 10,000 cattle at more than 5,000 farms had tested positive.
Within government, confidence that bans on offal and meat and bone meal would stem the rise in new BSE cases began to build and efforts shifted toward lifting the restrictions on British beef which had been imposed by other countries, including the European Union. But in April 1990, a Siamese cat in Bristol was to trigger a new wave of concern. Two vets at the city's university diagnosed the cat as having a feline form of BSE. While the government maintained the best course of action was to reassert the safety of eating beef, scientists knew the discovery was a turning point. "The argument that this disease was going to be safe to humans was based on it coming from scrapie, even though it hadn't caused problems before in humans," says John Collinge, director of the Medical Research Council's prion unit at University College, London. "When domestic cats started going down with it, we knew the disease had a new host range, and you couldn't say anything about whether humans were or weren't at risk. The problem was that people who stood up and said there might be a risk were quite severely leant on."
Late in 1990, it became clear that the ban on meat-and-bone meal was beginning to have an effect. The rate of increase of new BSE cases began to slow down. Banning the feed turned out to be the single most important measure in stemming the tide of BSE. "Getting that ban in place so quickly, even though it was incomplete, was remarkably effective," says Danny Matthews at the Veterinary Laboratories Agency in Weybridge. "When you could see what sort of tsunami was coming up, if we hadn't got the ban in place then, we really would have been in a disastrous situation 12 months later."
But fears that the disease might still strike humans were growing. Enormous quantities of BSE-contaminated beef had started pouring into the food chain in 1986. The incubation period in cattle meant that infected but outwardly healthy cattle had been processed into steaks, burgers, pet food and baby food. And scientists knew the disease, were it able to jump into humans, would take time to appear.
Behind the scenes, researchers were frantically trying to understand the infection. The consensus was that a new type of rogue prion was to blame. When it infected other animals, it forced healthy prions to change, and then spread the disease. Many experiments were insightful but not encouraging. In one test, sheep resistant to a major strain of scrapie contracted BSE after being fed just half a gram of infected cow brain tissue. Another test proved BSE could infect primates. Despite an emergency meeting of scientists to discuss the primate study, government assurances maintained that the risk to humans was remote. What they failed to make clear was that the scientists only felt the risk was low because of the raft of bans already in place. The studies made it abundantly clear that there was a grave risk for people who had already eaten infected meat.
The scientists' worries intensified when random inspections of abattoirs revealed that the offal ban was being widely flouted. In the mid-1990s, inspectors returned with tales of slaughterhouse staff claiming that they had been told to remove spinal cords from carcasses before cutting them up only two weeks beforehand. The revelation meant that cuts of meat contaminated by infected spinal cord had been finding their way into the human food chain for more than 10 years. Professor Collinge, who had recently joined the government's spongiform encephalopathy advisory committee, was dismayed. "It was clear the ban was a fiction and that it wasn't being policed," he says now. "But then, there were government ministers saying there was no conceivable risk [to humans], so how could we expect abattoir workers to go to extraordinary lengths to dissect out spinal cords?"
In 1995, one month after ministers formed a new Meat Hygiene Service to police the abattoirs, news came that an 18-year-old, Stephen Churchill, had died of a CJD-like disease. He was later identified as the first confirmed victim of vCJD. Two more deaths that year were also attributed to vCJD. "Very rapidly it became apparent that what we feared was indeed beginning to happen," says Collinge.
In 2000, 28 people died from vCJD, the largest death toll recorded in one year, bringing the total at the time to 84. In each case, the disease was as harrowing as it was unstoppable. It began with a change in personality: happy, confident young people developed mood swings, depression, lapses in memory. Some were prescribed antidepressants by baffled GPs. Others ended up in psychiatric wards. Then more symptoms emerged. Pins and needles, limb pain. Neurologists eventually diagnosed degenerative brain disease. Later on, unsteadiness would set in, then speech difficulties, incontinence, jerky movements and progressive immobility. While sporadic CJD, an illness that strikes at random and usually affects the over-60s, takes a few months to kill, vCJD was infecting mostly young people and killing them more than a year later.
From 2000, cases of vCJD began to tail off, but the threat is far from over and huge questions remain. Animal studies proved that less than a gram of BSE-contaminated material could infect cattle. In humans, the lethal dose remains unknown. Other unanswered questions are more worrying.
Many scientists believe two more waves of vCJD are looming. Genetic tests on vCJD patients reveal that all of them, so far at least, belong to 40% of the population who have what is called the MM form of human prion protein. When BSE infects a human, it is this form of prion that is most susceptible to changing and causing vCJD.
The remaining 60% of the population have different genetic variants of human prion (known as MV or VV). When they are infected with BSE, tests suggest their prions will still eventually misfold into a form that causes vCJD, only the process will take much longer. The upshot is that two future waves of vCJD could strike in the next 10 to 50 years.
The fear of future waves of disease is real: it is backed up by animal tests and studies of cannibalistic behaviour in Papua New Guinea. Research published in the Lancet last year supports the idea. Collinge's group investigated an epidemic of brain disease called kuru, triggered by cannibalistic rituals that were only banned in Papua New Guinea in 1950. Like vCJD, the disease is caused by a rogue prion. They found that, even without a species barrier to jump, the infection could linger unnoticed in people for more than 50 years. Disturbingly, the first to succumb had the MM form of prion.
According to Collinge, the prospect of two further waves of vCJD is just one possible scenario. It is possible, he says, that those who have already succumbed to vCJD are a tiny fraction of the population, who are especially susceptible not just because they have the MM form of prion, but because of other genetic traits. If he is right, a future wave of infections could be huge, as the less susceptible majority gradually develop the disease that infected them many years ago. "People think I'm being very pessimistic, but this will be part of the story. The only question is how big a part," he says.
The prospect of thousands of people harbouring the disease unknowingly has more immediate implications. Three people have so far contracted vCJD after receiving blood transfusions from donors who were unknowingly carriers of the disease. Among the victims was a woman with the MV form of prion protein, the first to be identified with vCJD. She died of other causes before the disease took hold. Worryingly, all had received the minimum transfusion of one unit of blood, proving the infection was easily passed on by contaminated blood. "The danger now is not from cattle, it's from other human beings," says Sheila Bird, an expert in vCJD at the MRC Biostatistics Unit in Cambridge.
The threat has forced the national blood service to bring in extensive measures to protect the blood supply. Anyone who has received a transfusion cannot donate blood themselves. Plasma is imported from the US. Other blood products are stripped of their white blood cells, which carry the infectious prions. The service recently began trials of new filters to "scrub" vCJD prions from blood. But there is still no blood test for vCJD, so it is impossible to know how much has been infected. If you receive a blood transfusion tomorrow, it could still be contaminated with vCJD.
Blood transfusions are not the only risk. Prions are not destroyed by the heating process that is used to make meat-and-bone meal and, likewise, they are not destroyed when surgical instruments are sterilised. Which means that surgeons operating on someone harbouring the disease could unwittingly pass it on via contaminated instruments.
Not knowing how many people are silently infected with vCJD is a gaping hole in scientists' knowledge, despite near-heroic attempts to find out. Last year James Ironside, at the CJD surveillance unit in Edinburgh, examined 11,000 organs from patients in the late 1990s and found two appendices and one other organ tested positive. The figure suggests that thousands in the general population could be carrying the disease.
Other serious attempts to find out will begin soon. Since 2003, the Health Protection Agency has been collecting tonsils from operations across the country. Tonsils test positive for prions in people diagnosed with vCJD, and the hope is that the prions are detectable before symptoms begin to show. The HPA now has around 35,000 pairs of tonsils at its site in Colindale, north London, and will begin testing them at the end of this month. In all, they will examine 100,000 pairs of tonsils to try to get an idea of the amount of vCJD in the general population, and should have their first figures in the spring. The effort is to be bolstered by plans to test organs for vCJD when they are removed during routine autopsies.
So far, a blood test for the disease has confounded scientists, largely because the infectious vCJD prions do not trigger an immune reaction and contain no genetic material. But if scientists are able to use autopsies or the tonsil archive to work out how many of us are infected with vCJD, the major unanswered question will be the most fundamental one: where did BSE come from?
Researchers are still divided on the issue. The theory that scrapie in sheep was to blame all along is still considered credible by some scientists, but others are convinced that a spontaneous mutation of healthy cattle prions was to blame, a mutation that could easily happen again, and may already have done so. Wherever it came from, it is clear that the practice of feeding infected cattle brains back to healthy cattle amplified the infectious prion and spread it to cattle across the country. "It's never a good idea to be a cannibal," says Higgins.
The fear of some researchers now is that, 20 years on, interest in answering the crucial remaining questions will wane. But leaving them unanswered would be a desperate mistake, says Professor Bird. "If that happens, we won't have all the information, and that's extremely dangerous".
