Expert doubts BSE will be eradicated in five years
BSE researchers bemoan 'ministry secrecy'
UK medical chief redefines safe
Swiss cull to meet fears of BSE
BSE experiment on monkeys 'a waste of time'
TSE infectivity in blood
Mad cow politics tries to corral science
BSE pre-dates rendering changes
Statistics suggest BSE now Europe-wide
Prion research programme proposed
:BSE transmission data cause confusion
BSE transmission data pose dilemma for UK scientists

Expert doubts BSE will be eradicated in five years

Reuter Information Service

BRUSSELS (Oct 9, 1996T) - Mad cow disease will probably still be around five years from now but the number of cases will be much lower, a leading expert hired by the European Commission said on Wednesday. Professor Charles Weissmann of Zurich University, who chaired a group of experts to look into research priorities, called for more work to determine whether the brain-wasting disease can be transmitted to humans and for development of a test for the disease on live animals and humans.

"I think it is pretty clear that it (mad cow disease) will diminish very considerably but whether it will go back to zero or whether there will be a low endemic level I don't think I would venture to predict," Weissmann told a news conference.

Speaking after presenting a report to EU Farm Commissioner Franz Fischler, Weissmann said that there were doubts about a report by Oxford University in England in August predicting that the disease would die out within five years and that an extra cull of cattle at risk to the disease was unnecessary.

"I am not quite sure that one can say that if all the sources of contaminated feed are eliminated that the disease will completely disappear," Weissmann said. Animal feed containing suspect tissue, such as ground up meat and bone meal, is believed to be the main source of the disease, known as Bovine Spongiform Encephalopathy (BSE). But Weissmann said more research was needed into how the disease could be passed from cows to calves and whether there were any hidden infectious agents.

On the link between BSE and its fatal human equivalent, Creutzfeldt Jakob Disease, experiments should be carried out on similar species to humans, such as monkeys, by giving them them increasing amounts of infected feed.

BSE researchers bemoan 'ministry secrecy'

10.10.96 Nature News

Scientific understanding of the epidemic of bovine spongiform encephalopathy (BSE) in British cattle has been delayed by the reluctance of the UK Ministry of Agriculture, Fisheries and Food (MAFF) to provide access to data, according to UK scientists. This reluctance, they say, has stemmed both from a 'culture of secrecy' at the ministry, and its failure to dedicate sufficient staff to analysing and distributing data on the epidemic.

Direct evidence of secrecy at MAFF comes from the uphill struggle faced by Roy Anderson, professor of zoology at the University of Oxford, and his colleagues, in gaining access to the confidential MAFF statistics needed to produce their recent analysis of the transmission dynamics and epidemiology of the BSE epidemic (see Nature 382, 787; 1996).

Indeed, Nature has learnt that MAFF agreed to make the statistics available only after senior officials at the Royal Society put pressure on government ministers, arguing that a credible analysis of MAFF data could be done only by independent experts.

Anderson's study was designed to estimate the number of infected cattle that may have entered the food chain undetected because they were slaughtered before showing clinical symptoms of BSE, and the efficiency of various culling policies designed to reduce the incidence of BSE. Both analyses required raw data on individual farms and the demography of herds, which -- according to several sources -- MAFF initially refused to provide.

"It was pretty clear that MAFF were scared about the outcome," says one scientist involved in the lengthy negotiations, suggesting that this was because the data would suggest -- as they did -- that many more sick animals had entered the food chain than was previously thought. MAFF eventually backed down and released the data, he says, after it had been persuaded that an independent epidemiological analysis of the BSE analysis was needed, given that Britain's European partners would be sceptical if this were done by MAFF, which would be perceived as having a vested interest in the outcome -- only in this way would other European countries be convinced that the study had been carried out "scientifically and properly".

Anderson declines to comment on this account of events. And a ministry spokeswoman dismisses allegations that it has been overly secretive, claiming that access to data is permitted within agreed collaborative projects. Requests for data that are readily available are met automatically, she says. Those for data that are more difficult to compile must be made through a more formal written procedure that includes a fee calculated on the basis of the amount and type of data required, and a pro rata charge for the salary costs needed to prepare it.

The spokeswoman last week promised that scientists can obtain all the data they need "as long as we deem it possible, and as long as the data doesn't infringe on the confidentiality of individual farmers or the data protection act". She declined to provide a copy of the detailed procedures for obtaining data, however, on the grounds that they had to be formally applied for through so-called 'open government' channels.

Not everyone has had problems. Several researchers acknowledge that MAFF has been helpful in providing relatively small sets of data. They point out that aggregated information has been made available, while MAFF's Central Veterinary Laboratory (CVL) in Weybridge has regularly published epidemiological studies. Similarly, Heino Diringer, a researcher at the Robert Koch Institute in Berlin, says that while he has never asked MAFF for statistical data, he has not encountered problems in obtaining other information.

But one scientist who has had difficulty obtaining data from MAFF complains of a "culture of confidentiality" among government ministries, and MAFF in particular. "This has worked to the detriment of the understanding [of the BSE epidemic] and dissemination of information in general," he says, pointing out that the health and environment ministries have better track records "in terms of being open and involving scientists from outside government".

"It has been a nightmare to get hold of comprehensive data," says John Kent, a statistician at the University of Leeds, adding that "not having the numbers more easily available has made life difficult". Kent is keen that MAFF should now make widely available the data used in the Anderson study so that they can be critically assessed.

Anderson agrees that this is necessary. But he points out that the database is not his to give, and that scientists must request it from MAFF. Mark Savey, a leading French epidemiologist working on BSE, says he has been given assurances by MAFF scientists that he will be given access to the particular datasets he wants.

Allegations of excessive secrecy within MAFF are confirmed by one MAFF scientist involved in BSE research. He says that while wider access to data on BSE might not have had much practical impact on the handling of the epidemic, MAFF's lack of openness has been "deplorable". "There is a general principle of not wanting to give the data to anybody. But then the political pressure became so great that it had to be given to the Anderson group," he says. "We shouldn't have been able to withhold data."

The MAFF spokeswoman defends the ministry's actions, however, arguing that its BSE database contains confidential information on individual farms, whose release is forbidden by current government policy; such databases must also respect the provisions of data protection legislation.

Anderson agrees that these factors are important. But he says that they are not insurmountable obstacles to the release of data, pointing out that the databases relating to the AIDS epidemic were made available to the entire scientific community "for analysis and interpretation".

Similarly, the spokeswoman argues that the general release of data could be misleading in the wrong hands. This view is supported by several scientists. "You can't make primary data widely available because it's too complicated," says one. "You need to first make a synthesis." Uncontrolled release of data could cause more problems than it solves, he says, through misinterpretation by both scientists and the press.

There is general agreement that complex databases should not simply be made freely available, as their proper exploitation requires an understanding of how the data have been assembled, and the various caveats they contain. But many scientists say that analogous problems in other areas -- such as census data -- are overcome by employing individuals to provide such assistance. The CVL would need an extra dozen people to do this, says one MAFF scientist. "It would take a lot of resources, but I think it would be well worth doing."

Indeed, MAFF's failure to assign sufficient staff to the analysis and distribution of BSE data appears to have been a major factor contributing to the difficulties faced by outside scientists. Graham Medley, a biostatistician at the University of Warwick, says he has benefited from greater cooperation from MAFF after having complained on a television programme about the problems of gaining access to MAFF data. Since then he has encountered few such difficulties, and attributes any that have arisen simply to the fact that the CVL is "inundated" with requests, and is "grossly understaffed".

Statistical research on the BSE epidemic within MAFF has been left mainly to a handful of researchers at the CVL. The small numbers of people involved is "staggering for a problem of this importance", says one scientist. Anderson says that, given the scale of the BSE problem, MAFF should have quickly assembled "a large and effective team collaborating with external teams with expertise in particular areas", and that this should have included researchers from other European countries.

Moreover, Anderson argues that cutbacks in government science over the past decade have made such external input more important than ever. These cuts have reduced the government's capacity to carry out the in-house research required to deal with complex scientific issues in many areas, he says. What is now needed, argues Anderson, is an interministerial body -- perhaps organized by the Office of Science and Technology -- that would assess important scientific issues, decide whether outside expertise was needed, and, if so, arrange for it to be brought in quickly.

UK medical chief suggests 'safe' does not mean 'no risk'

Nature News - 3 October 1996 The chief medical officer of the UK's Department of Health -- currently embroiled in political controversy over whether British beef is safe to eat -- has suggested standardizing the way in which risks are described to the public on a scale based on their severity.

Kenneth Calman proposes in his annual report, published last week, that the word 'safe' should, if used, "be seen to mean negligible" -- itself defined as "an adverse event occurring at a frequency below one per million". It should not, he adds, "imply no, or zero, risk".

Such a definition of negligible risk would, for example, include the chances of dying from being hit by lightning, or from the radiation released by a nuclear power station. It would also, on the basis of the most recent scientific evidence, include the chances of contracting Creutzfeldt-Jakob disease (CJD) by eating meat infected with bovine spongiform encephalopathy (BSE).

Calman's suggestions are put forward in a section of his report on "topics of particular importance". They are, he says, an attempt to "present a vocabulary for debate", adding that the perception of risk by the individual is "the most interesting but most difficult aspect of understanding risk".

He proposes dividing events into six categories, based on the chances of each occurring to an individual within any one year. These start with events of "high risk", where the risk estimate is considered to be greater than one in 100, and descend in a series of steps through "moderate", "low", "very low", and "minimal" to "negligible" risk, each encompassing events whose likelihood is an order of magnitude smaller than those in the previous category.

Calman acknowledges that any classification of a particular risk needs to be qualified by other words that may be equally important. These include whether the risk is avoidable or unavoidable; whether it is justifiable; whether it is acceptable or unacceptable (the latter meaning that it "would not be tolerated except for special reasons -- such as the use of unproven medical treatment as a therapy of last resort"); and whether the risk is "serious".

His categorization of risk has received a sceptical response from some public-interest and environmentalist groups. While acknowledging the importance of a more rational approach, these are concerned that events with any danger attached should not be officially labelled as 'safe' -- even if the risks are less than one in a million.

But Calman's scheme has, in general, been welcomed by industrial representatives such as those from the pharmaceutical industry, frustrated at what they argue to be the public's inability to distinguish the relative dangers posed by different kinds of risks. Britain's beef industry, for example, has slumped in the wake of the BSE scare, even though only about a dozen cases of CJD have been linked to 'mad cow disease' -- in a human population of almost 60 million.

Swiss cull to meet fears of BSE

Nature News - 26 September 1996 Switzerland's government announced last week that it has decided to subsidize the slaughter of 230,000 cows born before 1 December 1990 to restore the faith of consumers in Swiss beef. Feeding calves with animal protein, considered to be responsible for transmitting bovine spongiform encephalopathy (BSE), was legal until 1990.

Farmers will receive SFr1,000 (US$800) compensation for each cow slaughtered, and their use for human consumption will be banned. "This move is intended to restore to Switzerland the status of a BSE-free country," said the economics minister, Jean-Pascal Delamuraz.

BSE has already caused a serious economic problem for Swiss farmers. The domestic market has fallen by a third since the beginning of the year, leading to reduced beef prices and the decision to store large quantities of meat. Foreign markets have also been blocked, as the European Union -- of which Switzerland is not a member -- has banned the import of Swiss beef. The ban followed an announcement in March by the British government of a possible link between BSE and Creutzfeldt-Jakob disease in younger patients.

Switzerland has the second highest incidence of BSE in Europe, although, at 9.5 cases per 100,000 cattle, this is only one-hundredth of the UK level. "We intend to remove from the human food chain the entire cattle population which has a statistical chance of harbouring BSE-infected animals," says Heinz Mueller, a spokesman for the federal veterinary agency.

According to Mueller, the recent study by Roy Anderson and his colleagues at the University of Oxford showing that culling is likely to have only a limited impact on the extinction of BSE in the United Kingdom (see Nature 382, 779; 1996) is not relevant to Switzerland, as the objectives of the two countries are very different. "We want to rebuild trust in Swiss beef as soon as possible," he says.

The remains of Swiss cows born before 1990 will be used in animal feed given to pigs. But this is likely to cause problems. The two leading supermarket chains, Migros and Coop, announced last month that, in order to restore public trust in their products, they will stop selling meat from any species that is raised on feed containing animal protein.

BSE experiment on monkeys 'a waste of time'

The Times: Britain: October 10 1996
A LEADING European expert yesterday cast doubts on British forecasts that "mad cow" disease would die out soon and called for long-term tests using monkeys to establish whether it can be transmitted to human beings. A British scientist who has already transmitted BSE to monkeys said the experiment would be a waste of time.

After a year-long study ordered by the European Commission, Charles Weissmann of Zurich University said there were reasons to doubt the prediction by Oxford scientists that BSE would fall to negligible levels in about five years. "I am not quite sure that one can say that if all the sources of contaminated feed are eliminated that the disease will completely disappear," he said. The Government cited the Oxford forecast as the main reason for its decision last month to suspend a selected slaughter of cattle that was agreed in Florence last June.

Professor Weissmann said it appeared likely that BSE was transmissible to people through the consumption of beef. "The evidence we so far have is sufficiently suggestive of this transmission from cattle to man that we should act as though it were true."

The best way of establishing the facts was to start experiments in which monkeys would be fed increasing doses of BSE-infected tissue, the professor said. The long incubation time meant that the tests would have to be run over ten years. Monkeys were the best means because the "species barrier" was lower between humans and primates than any other animals. "The answer is that it will not be conclusive, but it is the best we can do under the circumstances," he said.

Ross Ridley, who works for the Medical Research Council in Cambridge, showed several years ago that BSE could be passed in the laboratory to marmoset monkeys by injecting infected material directly into their brains. This is thousands of times more effective as a route for infection than oral ingestion.

"Both the marmosets we inoculated developed brain disease after about four years," she said. "Subsequent comparisons have shown a resemblance to the pathology seen in human victims of the new variant of Creutzfeldt-Jakob disease."

Ms Ridley said she could see no point in the European experiment. "Once you have established what amount is needed, are you going to say that smaller doses do not matter? We have no way of translating a dose that is effective for a monkey into one that is effective for a human."

She added: "We have already shown that BSE can be transmitted to monkeys and hence that humans, if they ate enough, may also be able to get the disease. We have to assume that no dose of BSE is safe."

TSE infectivity in blood

Citations kindly provided by Roland Heynkes

Here are some references which reports TSE infectivity in blood. The very old article of Pattison et al. also demonstrated scrapie infectivity in muscle.

Casaccia,P.; Ladogana,A.; Xi,Y.G.; Pocchiari,M. - Levels of
infectivity in the blood throughout the incubation period of hamsters
peripherally injected with scrapie - Archives of Virology 1989;
108(1-2): 145-9

Diringer,H. - Sustained viremia in experimental hamster scrapie. Brief
report. - Archives of Virology 1984; 82(1-2): 105-9

Field,E.J.; Caspary,E.A.; Joyce,G. - Scra
pie agent in blood -
Veterinary Record 1968; 83: 109-10

Kuroda,Y.; Gibbs,C.J. Jr; Amyx,H.L.; Gajdusek,D.C. - Creutzfeldt-Jakob
disease in mice: persistent viremia and preferential replication of
virus in low-density lymphocytes - Infection and Immunity 1983 Jul;
41(1): 154-61

Manuelidis,E.E.; Gorgacs,E.J.; Manuelidis,L. - Viremia in experimental
Creutzfeldt-Jakob disease - Science 1978 Jun 2; 200(4345): 1069-71

Manuelidis,E.E.; Kim,J.H.; Mericangas,J.R.; Manuelidis,L. -
Transmission to animals of Creutzfeldt-Jakob disease from human blood
[letter] - Lancet 1985 Oct 19; 2(8460): 896-7

Pattison,I.H.; Millson,G.C. - Distribution of the scrapie agent in the
Tissues of experimentally inoculated goats - Journal of Comparative
Pathology and Therpeutics 1962; 72: 233-44

Tamai,Y.; Kojima,H.; Kitajima,R.; Taguchi,F.; Ohtani,Y.; Kawaguchi,T.;
Miura,S.; Sato,M.; Ishihara,Y. - Demonstration of the transmissible
agent in tissue from a pregnant woman with Creutzfeldt-Jakob disease
[letter] - New England Journal of Medicine 1992 Aug 27; 327(9): 649

Mad cow politics tries to corral science

Nature News - 19 September 1996

Science was this week once again called to the aid of politicians in Europe's 'mad cow' crisis, when the British government asked the European Commission to revise a previous agreement under which Britain would reduce the incidence of bovine spongiform encephalopathy (BSE) by culling 127,000 cattle.

The UK government has been reviewing the cull following the publication of an analysis suggesting that the epidemic phase of BSE would end around 2001 without any culling, and that, given the aetiology of the disease and uncertainty about which cattle are infected, its decline would not be greatly accelerated by any culling policy short of the slaughter of around a quarter of the 10 million cattle in the national herd.

But the interpretation of this analysis, which also puts estimated numbers on the level of infected cattle remaining in British herds, has also become a centre of controversy, with others contesting the claim that it undermines demands for a broad cull.

Speaking at a meeting of European Union (EU) farm ministers on Monday (16 September), Douglas Hogg, the UK agriculture minister, said that the paper concerned showed that "BSE will in any event die out in 2000 or 2001", and that there was no culling policy that "would make a substantial difference to the rate of decline".

The cull was originally agreed to by John Major, the prime minister, at the European Union summit in Florence in June, as the price to pay for an eventual lifting of the EU ban on the export of UK beef products. But Major needs parliamentary approval before the cull can go ahead, and this looks increasingly unlikely, given growing opposition among Tory members of Parliament.

There is also uncertainty about how the opposition Labour party will vote (opposing the cull would also win votes among farmers). With the prospect of an immediate lifting of the ban seeming increasingly remote, Major seems to be gambling on satisfying domestic interests at the risk of inflaming other EU governments, by demanding that the cull be reduced or abandoned.

The government is relying on the results of a study published by Roy Anderson, professor of zoology at the University of Oxford, and both academic colleagues and scientists working for the UK Ministry of Agriculture Fisheries and Food (MAFF). They used sophisticated modelling techniques and previously confidential MAFF statistics to analyse the transmission dynamics and epidemiology of BSE (see Nature 382, 787; 1996). They also compared the 'efficiency' of 14 different culling strategies, defined by the number of cases they eliminate for the total number of cattle culled.

But the European Commission disputes that the results undermine arguments in favour of the planned cull. The paper's estimates of the "efficiency" of various culling strategies -- in terms of how many cattle need to be killed to get rid of BSE cases -- are of no interest to the commission, says Gerard Kiely, a spokesman for Franz Fischler, the agriculture commissioner. "Whether it is 10,000 or 2 million cattle is irrelevant to us; what is relevant is reducing BSE [cases] as fast as possible," he says.

In contrast, Kiely argues that new evidence of maternal transmission of BSE -- which, as previously announced, has been submitted to Nature -- could, in fact, require an enlargement of the cull. The commission is open to reviewing the culling policy to take into account such data, he says, as it would allow "taking out more cases of BSE".

Like other critics, Kiely also points out that interpretations of the Anderson paper other than that of the British government are possible, and that the evaluation of the various culling strategies could similarly justify not a reduction but an extension of the planned cull. According to the Anderson paper, the agreed cull of 127,000 cattle would eliminate 1,580 cases of BSE. But by adding a maternally targeted policy and killing 150,000 cattle, 2,380 cases would be eliminated. "I think many member states would say that is the one we need," says Kiely.

Some scientists are also concerned that the British government has selected an interpretation of the paper that suits its political needs -- reinforcing the view that governments tend to accept scientific advice when it suits them and to reject it when it does not.

Mark Savey, a leading French epidemiologist on BSE, and a member of the BSE working group of the European Commission's scientific veterinary committee, also argues that the rapid interpretation given to the findings raises the wider problem of what he claims is insufficient discussion of research results in the BSE crisis.

"Non-scientists think that when a paper is published in a prestigious journal, it is the indisputable single truth -- that the matter is settled," says Savey. "But publication is only the first step; there is no paper in the BSE crisis that will close the discussion, and we will be discussing this disease for another decade."

In support of his arguments, Savey points out that much of the current literature focuses on the 'epidemic phase' of the disease. "It is a very British way of looking at things," he says. The British "say that BSE will be finished as an epidemic in 2001. What they don't say is that the disease will not have disappeared completely."

The scientific issue is to know whether the disease will remain sporadic, and how will this be handled, he says, pointing out that low levels of the disease in France has been enough to panic consumers. In a sporadic phase, BSE might evolve to find other routes of transmission, he warns, adding that the scientific community needs to "start thinking now" about these problems.

Savey also argues that, whereas the Anderson paper is "absolutely superb", the scientific aspects of the cull are merely one consideration. While scientific advice may influence culling policy, it would be simplistic to believe it should determine it, he says, arguing that this can only be done by also taking into account political, economic and other factors.

Certainly science, up to now, has had little to do with the decision to cull UK cattle. The cull was agreed by EU member states largely as a means of restoring public confidence in beef. But from the outset it has been opposed as lacking scientific justification by many scientific advisory bodies, including the British government's Spongiform Encephalopathy Advisory Committee (SEAC) and the World Organization for Animal Health.

Some British researchers argue, however, that the confirmation that any cull short of a massacre would not eradicate BSE any faster than doing nothing only lends weight to existing scientific criticism of the cull. "I suppose that is what the government is looking at, and I think the science supports it," says one of the paper's authors.

The epidemic should be allowed to die out naturally, given that precautions have been taken by abattoirs to prevent infected animals entering the food chain, says Ray Bradley, a MAFF scientist who is a member of SEAC and also chairman of the BSE working group of the European Commission's scientific veterinary committee. "The cull has no scientific basis," he says baldly. "It is only there to appease the other member states of EU."

BSE pre-dates rendering changes

Nature News - 11 July 1996

The bovine spongiform encephalopathy (BSE) epidemic pre-dates changes to Britain's rendering industry, according to new research published this week. Until now, the UK agriculture ministry has attributed BSE to rendering methods introduced in the 1980s.

The ministry has said that the new methods allowed the scrapie infective agent in sheep offal to survive and infect cows with BSE via cattle feed. But the results of new experiments funded in part by the European Union, the UK agriculture ministry and the UK's largest rendering company, Prosper De Mulder, shows that the scrapie agent remains active regardless of the choice of rendering method.

Statistics suggest BSE now Europe-wide

Nature News - 4 July 1996

Europe's veterinary surgeons have urged the European Union (EU) to introduce and enforce measures to ensure that bovine spongiform encephalopathy (BSE) cannot enter the human food chain. Their call comes as new analyses suggest that the incidence of BSE in continental Europe is much higher than officially reported.

EU member states in continental Europe have declared a total of around 50 cases of BSE. But some researchers estimate that these countries ought to have declared more than 2,000 cases, given that they imported large quantities of breeding cattle and potentially contaminated meat and bone meal from the United Kingdom

One explanation for this discrepancy, say observers, is that farmers may have been discouraged from reporting cases because many countries slaughter herds where BSE has occurred without adequately compensating farmers.

These estimates of the number of BSE cases in continental Europe are nonetheless an order of magnitude lower than in the United Kingdom, where around 160,000 cases have been reported. It follows that any impact on human health would be correspondingly lower, even if it was established that the agent that causes BSE can pass to humans and cause Creutzfeldt-Jakob disease (CJD). Experts also point out that most of the BSE cases in continental Europe will already have entered the food chain.

Nevertheless, at a meeting in Paris last month, the Federation of Veterinarians of Europe (FEV) acknowledged the BSE crisis is now a "European problem" -- and not just a British one -- according to one official present. Tougher European measures to protect public health are needed, he argues.

He points out that, until last week, when France banned the human consumption of specified bovine offals (SBO) -- the most infective parts, such as brain and spinal cord , the United Kingdom had been the only EU country to have done so. (Switzerland, which is not a member of the EU, had introduced a similar ban.)

To reassure consumers, "it must be demonstrated beyond any doubt that BSE cannot enter the food chain", says Francis Antony, president of FEV and the British Veterinary Association's spokesman on BSE. In a statement last week, FEV called on the EU to "design, apply and enforce" a comprehensive food hygiene programme "from the stable to the table".

"Consumer perception and the scientific reality of food safety are too far apart," says one FEV official. "The key issue is about keeping brain and spinal cord out of the food chain." Indeed, the FEV statement seems a thinly veiled attack on what one official says is the EU's excessive focus on the culling of UK cattle.

Although culling will precipitate the decline of the epidemic in cattle, it will have little direct impact on human health, argues one FEV official. Eliminating risk to public health requires a ban on the human consumption of SBOs and strict enforcement of deboning and denerving procedures in abattoirs to eliminate infective tissues.

The EU also needs to ensure that adequate resources are made available to enforce any new regulations, says one FEV official. The failure of the United Kingdom to police its early feed and SBO bans has shown that "you can ban things until you are blue in the face", but without proper enforcement this has little impact.

The revised estimates of cases of BSE in mainland EU states come from analyses of UK exports of animal feed and live cattle. Experts predict that imported feed may have resulted in several hundred cases of BSE. But the total is difficult to estimate precisely because the final destination and use of feed are often unknown, while the relationship between tonnage and infectivity is difficult to establish, according to John Wilesmith, of the UK Ministry of Agriculture's Central Veterinary Laboratory in Weybridge.

Better estimates may come from analysis of UK exports of breeding cattle. One group of researchers has estimated, for example, that the United Kingdom exported 57,900 pure-bred breeding bovines between 1985 and 1990, the latter being the year after the EU banned imports of breeding animals older than six months.

One of the scientists, B. E. C. Schreuder from the DLO-Institute for Animal Science and Health in Lelystad, the Netherlands, says that, statistically, around 1,700 of these animals would be expected to have developed BSE.

Such estimates must be taken with caution because of the assumptions they involve, says Schreuder. His estimates of total exports are somewhat higher than records of exports for "pure-bred breeding bovines" provided by Eurostat -- the body that supplies the European Commission with statistics -- as he has also included other export categories such as "bulls not intended for slaughter".

Nonetheless, Schreuder is confident that their estimate of BSE cases in continental Europe attributable to cattle exports is of the right order of magnitude. He says it is possible to identify the individual member states most at risk -- Portugal, which has declared just 30 cases of BSE, is expected to top this list.

Schreuder says that his warning of under-reporting is mainly aimed at countries where lack of regulation might yet allow recycling of BSE and new outbreaks. Wilesmith adds that better data on true BSE levels in continental Europe will be essential to studying the epidemiology of any cases of the new variant of CJD that arise there. The evidence for higher levels of BSE on the European mainland also underlines the need for an effective European CJD surveillance network, he says (see Nature 381, 453; 1996).

Wilesmith asserts that "we were lucky there were not BSE epidemics elsewhere". The factors that led the United Kingdom to be worst affected, he says, probably included the world's highest ratio of sheep to cattle (45 million to 12 million), a high prevalence of scrapie, and the use of high proportions of meat and bone meal in cattle feed.

Other countries may have escaped relatively unscathed only because they had more cattle than sheep, low levels of scrapie, or used less meat and bone meal in cattle feed. Indeed, a new report from the UK Institute of Animal Health suggests that the procedures used in many rendering plants throughout Europe would have been insufficient to inactivate the agent that causes BSE.

Prion research programme proposed

Nature News - 27 June 1996 The European Commission has proposed setting up a ECU100-150 million (US$123-185 million) research programme into BSE and other prion diseases. The commission raised the matter at the European Council meeting in Florence last weekend, and is expected to follow this up with a formal proposal in the near future.

The commission is asking that funding for the programme should be additional to existing allocations for research, and should come from other European Union (EU) budgets. A call for proposals would be issued for research to characterize the agents responsible for prion diseases, and to reinforce clinical research on Creutzfeldt-Jakob disease (CJD). The commission is also seeking to coordinate and strengthen CJD surveillance networks.

Meanwhile, the commission has also agreed to set up a multidisciplinary committee on BSE intended to "ensure that the scientific advice on BSE given to the commission takes into account the widest possible range of expertise". Members of the committee will be chosen by a seven-member steering group, which includes Robert Will, head of the UK National CJD Surveillance Unit.

The new committee will be only consultative, and political power remains in the hands of the agriculture directorate's Standing Veterinary Committee, recently criticized for allowing its judgement to be influenced by political factors (>see Nature 381, 353; 1996).

BSE transmission data cause confusion Nature News - 1 August 1996

The possibility that bovine spongiform encephalopathy (BSE) might be transmitted from cattle to sheep caused widespread concern and confusion last week. Franz Fischler, the European Union's Agricultural Commissioner, responded to what he described as "experimental evidence" by calling for a ban on various sheep and other ruminant tissues entering the food chain. Research by the UK Institute of Animal Health has found that sheep selectively bred for resistance to natural scrapie, a disease in the same family as BSE, could still be infected by brain extracts from cattle suffering from BSE. Tissues recovered from one such sheep, out of six fed the infected material, induced a disease in mice with incubation periods and pathology closely resembling those caused by direct transmission of BSE from cattle to mice.

Although the pathways of the disease seem to be different in cattle and sheep -- only sheep showed infectivity in the spleen -- the results have been taken to indicate a theoretical risk. Douglas Hogg, Britain's agriculture minister, says he is treating this with an "abundance of caution", recommending that sheep heads are destroyed in the same way as those of cattle.

Chris Bostock, head of molecular biology at the institute, describes the ban as a "sensible precaution". But he points out that, due to the similarities between BSE and scrapie, distinguishing between them when diagnosing sheep may be very difficult. But concerns that scrapie in sheep could be masking BSE have come from "people speculating", says Francis Anthony, a spokesman for the British Veterinary Association.

BSE transmission data pose dilemma for UK scientists

Nature News - 8 August 1996 Preliminary research results have confirmed fears that a small proportion of cows infected with bovine spongiform encephalopathy (BSE) can pass the disease on to their offspring, a conclusion that may directly affect the UK government's cattle slaughter programme.

The reported low rate of maternal infections -- ten per cent in the offspring of BSE-infected cattle, and an estimated one per cent or more in the national herd -- is not expected to affect overall BSE levels. Those ''are falling at a rate of 40 per cent a year", according to the Ministry of Agriculture.

An announcement on maternal transmission of BSE had been expected (see Nature 381, 724; 1996). But its timing has fuelled further controversy in the United Kingdom and Brussels. Although the 12-member UK Spongiform Encephalopathy Advisory Committee (SEAC) discussed the results at a meeting on 19 July, the official government announcement was made on 1 August, days after parliament closed for the summer.

Opposition politicians are accusing the government of deliberately withholding the results. But Sir John Pattison, chairman of SEAC and vice-provost of University College London, says the time between SEAC's meeting and the announcement was spent reviewing the findings and drafting a statement for government. Pattison says SEAC assessed the data in less than two weeks. "I can't see how we could have acted faster."

This is the second time that SEAC has decided to release results before the scheduled completion of an experiment -- or, indeed, its peer-reviewed publication in the scientific literature. The first occasion, when preliminary results suggested an association between the consumption of BSE-infected beef and a new strain of Creutzfeldt-Jakob disease, the human equivalent of BSE, helped to trigger the current beef crisis (see Nature 380, 273; 1996).

Francis Anthony, BSE spokesman for the British Veterinary Association, says he was "annoyed" when he heard that preliminary data had been released. "I believe there is a case for the scientists [conducting the experiments] to dig their heels in and say: 'we'll give the results when we're ready', otherwise they could be accused of doing bad science."

But Anthony acknowledges SEAC's dilemma. It had to act quickly in the interests of health, while ensuring the accuracy of the research being publicized, "particularly as I have been urging the government since 1988 to outlaw breeding from the offspring of BSE-infected cattle".

Sir Richard Southwood says the decision to release early data is justified on this occasion. Southwood, professor of zoology at the University of Oxford, was the chairman in 1988 of the government's first advisory committee on BSE, whose recommendations led to the setting up of the maternal transmission experiments. "I know this is a thorny problem," he says. "But this is an important matter. In an ideal world we could wait. But science cannot operate in a vacuum from political, economic or social considerations."

Pattison says the results were released after SEAC members had assured themselves that waiting for further analysis would not have altered the thrust of the findings. "We couldn't just sit on this, and felt we had to tell the government. We knew that a culling policy would need to take account of maternal transmission," he says.

Pattison adds that, if SEAC had waited until the end of the experiments, it would have been accused of endangering public safety. But he acknowledges the dangers of creating an expectation among the public and politicians of the automatic early release of research results, and hopes it will not happen with further BSE-related experiments. "Peer review is absolutely critical; it is the essence of how we operate."

The latest findings come from a seven-year project begun in 1989 at the government's Central Veterinary Laboratory in Weybridge, Surrey. The research compared rates of BSE infection in the offspring of two groups of cattle; analysis of the results has been complicated by the fact that, at an early stage in the experiments, many calves were fed with potentially infected feedstuff.

Of 333 calves born to mothers with BSE, 273 had died by 14 July. Initial histological examination showed that 42 suffered from BSE. An equivalent group was the offspring of BSE-free cattle. Thirteen of these animals had developed the disease. A comprehensive analysis of all the cases would have taken another year.