This week Richard Lacey gave evidence to the public inquiry into BSE. Here he criticises scientists for their continuing ignorance about the disease and warns that 18 million people could fall ill
It is sad that 12 years on from England's first case of mad-cow disease, or bovine spongiform encephalopathy, knowledge of the disease is still scant. I hope that the public inquiry that opened last week will provide answers but, in the popular imagination, there is only horror at the way in which the disease spreads and at the fear created by half-truths and rumours. Is BSE passed from sheep to cows and then to people - causing a new and dreadful variant of the progressive and fatal dementia, Creutzfeldt-Jakob disease? Is it the result of a new type of cannibalism, the eating of meat-eating cattle? Can it turn the human brain soft and spongy? Will it result in an epidemic with millions of fatalities? What bits of the cow are the most fatal? The lack of facts has made the public only more frightened.
Even scientists understand little about the illness. This is partly because it is difficult to develop tests to detect the disease. Unlike all other infectious diseases, transmissible spongiform encephalopathies - of which BSE is one form and CJD probably another - do not provoke an immune response. Because cells do not produce antibodies to resist the infection, as they do in the case of AIDS, tests based on antibody production cannot be set up.
Moreover, the chief cause of TSEs - what is called a prion, a protein that can cause further similar proteins to be produced in cells - is a tough opponent. It is difficult to destroy using disinfectants or sterilising methods.
Tracking the disease is also difficult. There is a long incubation period before the final distressing illnesses of TSEs emerge, and in that period the disease can spread. Unlike HIV, which has a predilection for people, the causative prions of TSEs can probably infect several species, including cats, cattle and humans.
The crucial year was 1985. Before then, TSEs under "natural" conditions had been identified in only six mammals - humans, sheep, goats, mink, elk and deer. Since 1985, TSEs have cropped up in 13 new species, including zoo cats, domestic cats, antelopes and even ostriches. The most significant medical finding has been the discovery of a new type of CJD in humans. The old type of CJD usually manifested itself in people of 65 or older, the final illness lasted about seven months and dementia occurred early on. In the new variety, sufferers have been as young as 16, the illness lasts an average of 14 months and dementia sets in fairly late.
The inevitable inference is that BSE causes the new variant of CJD (nvCJD), although it is uncertain how the disease jumped from cattle to people. The most likely way is via eating beef products, particularly those containing offal. Drinking milk cannot be ruled out as a cause, even though, in experiments, milk did not transfer the disease to mice.
Where did BSE come from? United States research published in 1994 showed that the disease sheep scrapie did not cause BSE (no similar research was performed in the United Kingdom, a terrible indictment of the authorities at the time). What that meant, and contrary to what was thought until recently, was that cattle's eating of sheep brains was not the cause of BSE. So what was?
One possibility, and I believe this to be the most likely, is that BSE is a variant of a rare similar cattle disease that was responsible for the earlier types of CJD in many countries. That BSE arose initially in the UK would then be a matter of chance, because cannibalistic cattle feeding - cattle being fed the carcasses of other cattle - was widespread in the developed world.
The second possibility is that BSE sprang from the remains of another animal. The culprit could be domestic cats that had been put down by vets, who disposed of their carcasses in rendering plants, which then added the resulting meat and bone meal to cattle feed. TSE in cats is very like BSE. However, the first TSE in a cat was not reported until 1990, making it more likely that infection spread from cattle to cats than the reverse.
Third, it is just possible that human remains entered rendering plants and then passed into cattle feed. It has been reported that human placentas were fed to Swiss cattle, and if BSE was caused by CJD, it might explain why the new variant CJD and BSE are virtually identical. But this is unlikely.
Research has shown that TSE infection can be transferred in several ways: through eating, direct blood contact or from a mother to her offspring before birth via the umbilical cord. Transfer by semen is also theoretically possible. CJD has been acquired by blood transfusion, grafts,transplants and injections into children of contaminated hormones from pituitary glands (growth hormones). It is even possible that buried infected animals might contaminate water supplies.
Regrettably, little is known about how the BSE prion spreads within cattle to produce the final brain disease. But, by analogy with other TSEs,it is possible to paint a general picture that is relevant to predicting which parts of the cow might be most infectious to humans. We know, for instance, that the greater the dose of infection entering an animal, the shorter the time before fatal brain damage sets in. We also know that the way the prion enters the animal does not determine the course of the disease and that the first cells the prion attacks are those related to immunity. These are found mainly in the guts, spleen, thymus and tonsils, and this is why these organs (and the brain and spinal cord) have been removed from cattle aged six months or older at slaughter since late 1989. However, these cells are also found in many other tissues, including liver,blood, bones, lungs and lymph nodes.
The infection probably reaches the brain through the blood and, once in the brain, gradually destroys the nerve cells, causing irreparable brain damage. Greatest infectivity is thus found in the animal's brain after death, sometimes to such a degree that a single gram of tissue can infect ten thousand million mice.
One of the problems with investigating BSE is that experiments have been done not on calves but on a breed of mouse that is barely vulnerable to the disease. The only organs that have infected mice fed with cattle remains are the brain, spinal cord, optic nerve and intestines. This does not, however, mean that other bits of diseased cows are not infectious. Indeed, we think that infectivity is widespread through the bodies of cattle with BSE. Since the disease is passed on from cow to calf in about 10 per cent of cases, it seems it must be passed through blood.
How many people might succumb to nvCJD and when? Any figure is nothing more than a guess. Apparently, 18 million people possess the right genes to have the potential to develop CJD, if infected. A worrying possibility is that some people may incubate the disease but appear healthy. Such carriers might transfer the infection in ways comparable to the spread of HIV, eg blood transfusions, surgery, transplants or sex. The uncertainty in making predictions is due to the variation of the incubation period. For example, if those already diagnosed with nvCJD caught it in the early or mid-1980s when BSE was rare, we might expect many more cases to emerge soon in those exposed to the infection a few years later.
If the incubation period turns out to be about 30 years, the omens are gloomy. This last prediction is based on the analogy with cattle, where by 1996 only 80 BSE cases out of about 160,000 (ie 0.05 per cent) were in animals aged under 30 months. The average age of BSE cattle is about five years. It would be reasonable to expect that people, who live much longer, would experience a much longer incubation period.
Because the infection causing TSEs can pass between animals in various ways, loiter in the environment for years, and as there is still no practical means of identifying which animals are incubating the disease, the only absolutely safe course of action is the slaughter of all infected herds and their replacement with BSE-free stock. This policy has been adopted by other countries. But it seems as if the potential cost of this policy, together with the inadequate facilities for disposal of unwanted cattle remains, puts it beyond our capability. The current policy of preventing the carcasses of cattle aged over 30 months from entering the food chain is evidently a compromise.
Unfortunately, avoiding eating beef from cattle aged over 30 months does not completely wipe out the risk of contracting nvCJD. Because calves can be infected at or before birth, younger animals will carry some infection. Pregnant women, young children and people from abroad who have never been exposed to British beef should not eat beef at all.
While some of the details of BSE remain disputed, the cause has to be attributed to intensive farming, centralised food production and the consumer demand for cheap, convenient dairy products and beef. Almost as soon as the disease was identified, its scale was such that the political and economic cost of attempting to eradicate it was beyond that of the government of the time. The message is simple: when centralised food production goes wrong, the consequences are devastating. This is the price the urban dweller pays for cheap food.
My analysis is pessimistic. The previous UK government and the farming industry came up with an alternative assessment that played down the health risks and played up the economic harm being inflicted on farmers. The hysteria over BSE was not justified, according to their argument, and the real need was to encourage the consumption of British beef, said to be the best in the world. In other words BSE is a problem of consumer confidence. This view may or may not be correct. Right now, we do not know.Science has failed to deliver the facts. Scientists have failed us, and that failure shamefully has allowed the disaster to escalate unchecked.
Richard Lacey is professor of microbiology at the University of Leeds.