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Meat industry fears controls after warning from scientist
Urgent need for faster diagnostic test
Doubts over ability to monitor risks of BSE spread to sheep
Nose drops may improve treatment of Alzheimer's
Atlantic Monthly article is on the Web
US nutritional supplements questioned

Urgent need for faster diagnostic test

Declan Butler  3 September 1998 Nature press release
Paris. Sheep BSE research is hampered by the lack of a highly specific diagnostic test suitable for field use. Conventional strain typing, pioneered by Moira Bruce at the BBSRC's Institute for Animal Health in Edinburgh, discrimates prion strains well, but involves inoculating legions of mice with sheep extracts, and analysing incubation times and lesion profiles in the brains of mice that succumb. Experiments take up to two years, and each costs 30,000.

John Collinge, head of the Prion Disease Group at Imperial College School of Medicine in London, and a member of SEAC, thinks he has a faster and cheaper method, but complains that the UK agriculture ministry has so far failed to commit itself to the refinement and scaling-up of the technique needed if large numbers of sheep are to be tested.

The technique distinguishes prion strains on the basis of Western blot patterns of conformation and glycosylation of prion proteins, and Collinge says pilot studies demonstrate its feasibility in screening for BSE in sheep.

But many scientists, including Stan Prusiner, who received the Nobel prize last year for his work on prions, remain sceptical about the theoretical basis of the method. Others question its validity in sheep where interpretation of patterns is complicated by the large variety of prion strains and host prion genotypes. The electrophoretic profiles of the many sheep prion genotypes needed to establish a baseline for comparison has also not yet been established.

Such uncertainties have divided SEAC members over the use of the technique. "It is not coming out clean in a way that makes it easy for us on SEAC to make decisions," says one SEAC scientist. These arguments miss the point, says Collinge, who argues that, even if the theoretical basis for his technique is not clear, it is an empirical marker that works. He admits the technique needs refinement: "But that's MAFF's job not mine."

Opinion on SEAC now seems to be swinging in Collinge's favour. Pattison says: "Glycotyping is likely to be one of the useful techniques in surveying the strain characteristics of the agents recoverable from a large(ish) number of animals. I think we've reached the point where accumulation of further data is the way to inform ourselves about the usefulness of the technique rather than further theorizing."

One compromise strategy that seems to be emerging from SEAC discussions is that, in the absence of a rapid specific test, a targeted search could use Collinge's technique to screen several thousand scrapie cases and identify suspicious signatures which could then be double-checked using the traditional strain-typing technique.

Some of the resistance to Collinge's technique seems, however, to be linked to fears that a preliminary diagnosis of BSE in sheep using this method may be interpreted by the public as firm evidence that BSE has passed to sheep. "The consequences of identifying a first case of BSE in sheep would be catastrophic so we need to be really sure [about the reliability of the identification]," says one member of the European Commission's independent Scientific Steering Committee.

Doubts over ability to monitor risks of BSE spread to sheep

 Declan Butler  3 September 1998 Nature press release
Paris. Has 'mad cow disease' BSE infected sheep in the United Kingdom? Scientific advisers to the UK government and the European Commission are calling for research to assess the risks to be stepped up. Scientists studying bovine spongiform encephalopathy agree on one thing: that there is a very real risk that BSE may have passed into flocks of sheep and goats in the United Kingdom and elsewhere.

UK sheep were fed BSE-contaminated meat and bone meal until the July 1988 feed ban, and limited experiments have shown that sheep fed infected cattle brain can succumb to BSE. It remains unknown whether BSE has entered the UK sheep population, but is going undetected because its symptoms are indistinguishable from those of scrapie, a spongiform encephalopathy endemic in UK flocks, but which does not seem to transmit to humans. However, if BSE has really passed into the sheep population, the consequences for human health could be extremely serious. "We could be facing a potential national emergency," says one member of the UK government's Spongiform Encephalopathy Advisory Committee (SEAC). Given that BSE seems capable of infecting humans via the oral route, SEAC judges that infected sheep tissues could likewise "pose a potential risk to human health if eaten".

SEAC, which reports to the agriculture ministry and the health department, confirmed last month that the total number of UK cases of new-variant CJD, the human version of BSE, is 27. Epidemiologists say it is still too soon to reach any conclusions about the scale of any epidemic. Not enough research is being done to assess how significant the danger of sheep BSE might be, according to many scientists. Unease persists within SEAC which is to set up a sub-committee to draft proposals for a large expansion of research. The European Commission's independent Scientific Steering Committee is also scheduled to recommend more research at the European level

This year the UK Ministry of Agriculture, Fisheries and Food (MAFF) is spending 2.8 million (US$4.6 million) of its 12.7 million BSE research budget on sheep spongiform encephalopathies, and the Biotechnology and Biological Sciences Research Council has budgeted 3 million over the next three years.

In July 1996, SEAC recommended more research to establish levels of scrapie in sheep and to assess the risks of BSE. An abattoir survey of the incidence of scrapie in sheep brains, suggested by the committee, began in August 1997, while the MAFF imported more than 1,000 scrapie-free sheep from New Zealand at the beginning of this year for pathogenesis and transmission research.

Sir John Pattison, SEAC's chairman, says the new subcommittee "will be the best way of developing specific recommendations". A MAFF spokesperson declined to comment on research needs before the subcommittee has delivered its recommendations, but said MAFF would follow SEAC's advice.

SEAC members admit that, as a result of the current insufficient effort to detect BSE in the sheep population, decisions on public health measures are based on uncertainty rather than science. Epidemiological data on scrapie-like cases is so poor throughout Europe that it is impossible to even tell whether the incidence has changed over the past decade .

Scientists are particularly concerned about the speed and scale of experiments to detect BSE strains in sheep. Conventional strain typing studies to distinguish scrapie from BSE are burdensome and take years. So far, results from only nine UK sheep isolates have been published.

Jack Cunningham, until recently Britain's agriculture minister, has publicly interpreted these results as reassuring: "So far all the samples studied have revealed scrapie and not BSE. Scrapie is a disease endemic in the UK and France for over 200 years and which is to our knowledge, while analogous to BSE, harmless to man."

Many scientists are more cautious. "Having found zero out of nine, what confidence can we attach to the statement 'BSE is not present in sheep'?" asks Jeffrey Almond, a virologist and professor of microbiology at the University of Reading, who is a member of SEAC. "The answer is very little; 'absence of evidence' is often confused with 'evidence of absence'." He points out that, to have a hope of detecting BSE levels as low as 0.1 per cent of supposed scrapie cases, for example a level that would have significant consequences for public health thousands of scrapie cases would need to be screened (see corresponding article). [what article? webmaster}

Until the risk of BSE in sheep is better assessed, scientific advisers are left contemplating an unknown risk. If BSE had entered the sheep population in the 1980s it may still be present. SEAC considers that, whereas cattle are a dead-end host for BSE, there is evidence that in sheep BSE behaves like scrapie. Scrapie is transmitted from animal to animal and is endemic, and they suspect that BSE in sheep might behave similarly.

The BSE prion shares characteristics with scrapie in sheep. The distribution of BSE infectivity in experimentally infected sheep mirrors that of scrapie and not that of BSE in cattle, with infectivity being present in a wider range of organs. The possibility remains that BSE was introduced in the sheep flock in the mid-1980s and has persisted, says Almond.

The wider distribution of infectivity of BSE in sheep also suggests that effective precautions to protect the public might be more difficult to make than in cattle, and that existing measures might be inadequate if BSE were to occur in sheep. UK measures, based on SEAC recommendations, include the compulsory slaughter of sheep and goats with scrapie with compensation for farmers, and a ban on clinically affected animals and the heads, spinal cords and spleens of all animals entering the human or animal food chains. Similar measures have been adopted in France, but not throughout the European Union.

But SEAC acknowledges that, if BSE behaves like scrapie, it "would also be present in the lymph nodes, spleen and parts of the intestine in medium titres in animals in the preclinical phase". "If you wanted to minimize risk you would have in practice to condemn the entire carcass," says Almond.

Almond justifies SEAC's decision to stop short of such drastic recommendations. "To do nothing would be inappropriate," he says, "while banning lamb would be ridiculous." It would not be possible to justify killing the entire national flock when not a single case of BSE had been identified, he says. "We had to find a middle ground, which we call a 'risk reduction strategy' as opposed to a 'risk minimization strategy'."

If new research identified BSE in sheep, SEAC would consider stricter measures, according to one member of the committee, who defends what he describes as an "incremental approach" that adds new measures according to perceived need. Lack of scientific data on the risks has placed SEAC in a position analogous to that of the scientists who advised the government at the beginning of the BSE crisis, admits one member. "We are back to square one," and "in a very, very difficult position" in recommending appropriate courses of action.

Also in a difficult position is Britain's new Labour government. In its handling of the risk of BSE in sheep, it is in danger of repeating the mistakes made by its Conservative predecessors in their management of the BSE beef crisis, warns the UK Consumers' Association. The association wrote to Tessa Jowell, the minister of state for public health, on 10 August complaining that the government was not keeping consumers properly informed about the BSE sheep issue, and excessively concentrating decision making in the hands of experts. The confidential letter contests SEAC's recent public recommendation that no further controls such as a ban on lamb offals are needed at present.

Sheila McKechnie, the head of the association, argues that SEAC's role should be limited to advising the Department of Health on the state of the science. Public health requires not only a scientific judgement but "a political and social one," she argues, which is the responsibility of government and not experts. "I find this very distressing," says McKechnie, "it is like history repeating itself".

SEAC also needs to explain more clearly to the public the rationale of its advice to government, argues Harriet Kimbell, a lecturer at the Guildford College of Law, and the first consumer representative on SEAC. "The public should be able to make the same informed judgements on their eating habits as I, as a member of SEAC, can." Kimbell claims SEAC is reluctant to make this cultural change "it is not the most open of bodies," she says. Pattison was unable to be reached for comment on this.

The letter to Jowell also called on the health department to consider advising parents not to feed lamb to young children, "who may not have been exposed to previous risks of BSE and not have eaten lamb so far". The letter argued that until the risk was better quantified this might be justified on the basis of "the public health principle of both precaution and proportionality".

The letter added that the association rejected concerns that "to issue any kind of statement would result in media hysteria and cause major damage to the industry," arguing that this was the policy taken by the previous government. SEAC dismissed the association's suggestion, and DOH has since said it does not intend to issue any further advice at this time.

The quality of the reasoning by some SEAC members is open to debate, however. One member criticizes the association's proposal, arguing that: "If you start saying don't feed lamb to children all hell will break loose." Another says: "I did not understand why children would be at a higher risk than adults, there may be actual reasons to speculate on that, but those would hardly be sufficient to justify such selective precautions."

Nose drops may improve treatment of Alzheimer's

Reuters News Service September 2, 1998
LONDON - Nose drops could transform the treatment of Alzheimer's disease and other illnesses that waste away the brain, New Scientist magazine reported Wednesday, citing recent research by a neuroscientist in Minnesota. The magazine said that the nasal passage, which provides a direct link to the brain, could be the ideal conduit for delivering therapeutic drugs that cannot reach the brain through the blood.

The molecules of many drugs are so large they cannot cross the blood-brain barrier -- cells in the blood vessels in and around the brain that form a kind of barrier to guard brain tissue. Finding an effective method of delivering drugs directly to the brain has been a stumbling block in treating neurological diseases.

The neuroscientist, William Frey of the Alzheimer's Research Center at the Regions Hospital in St. Paul, Minn., thought nose drops could be an ideal way to get a new treatment for the disease into the brain. "I knew that bad things could get in this way. It occurred to me that maybe good things could get in this way too," he said.

He and his colleagues tested the theory on 12 rats. Half were given the treatment in nose drops and the rest in an injection. Within an hour of treatment Frey found that the treatment given in nose drops had reached the hippocampus, amygdala and other regions of the rats' brains not involved in smelling. In contrast, the rats that received injections had very little of the treatment in their brains.

"The nose, they say, could deliver drugs not only for Alzheimer's disease but for a range of other neuro-degenerative conditions as well, including Parkinson's disease and multiple sclerosis," the weekly magazine said. Frey's team also used nose drops to administer insulin growth factor 1, a treatment for strokes, and found similar results. They will report their findings at a meeting of the American Association of Pharmaceutical Scientists in San Francisco in November.

Atlantic Monthly Article is on the Web

 Atlantic Monthly article by Ellen Ruppel Shell on mad cow disease in USA
A few colorful quotes from a 13 page article:

'In fact, brain doesn't just enter our food chain but goes directly into the human food supply. Each year, according to the USDA's Food Safety and Inspection Service, which is charged with regulating the meat industry, about a million cow brains are sold for consumption in the United States, and others are exported. Generally these are whole brains taken from cows slaughtered in the kosher manner -- that is, their throats are cut while they are still conscious. Most cows in the United States, though, are shot in the head with a stun gun before having their throats cut, a process perhaps more humane but also, at least when a pneumatic stun gun that injects air is used, more likely to contaminate other parts of the carcass with brain. This pneumatic gun can crack the cow's skull, causing the brain to leak out. And the force of the gun is such that it can blow pieces of brain into the bloodstream, where they can be carried to the animal's lungs or liver. Tam Garland has recovered chunks of brain as large as six inches across in the lungs of slaughtered cattle. Canadian researchers have spotted pieces of brain about two and a half inches wide lodged in cow livers.'

'Will Hueston, a veterinary epidemiologist formerly with the USDA and now an associate dean at the Virginia-Maryland Regional College of Veterinary Medicine, says that the agency has not imposed a ban on spinal column and brain in the rendering process because to do so would be very expensive and basically unenforceable. As one rendering-plant employee told me, "Who would want the job of cutting out all those spinal columns and brains? You couldn't even get occasional workers to do it." But when asked why brain and spinal column are not banned from the human food supply in the United States, Hueston was circumspect, suggesting that I speak with someone at the Food Safety and Inspection Service.'

'Jacque Knight, a spokeswoman for the FSIS, was vague and seemed annoyed when asked whether brain or spinal cord was getting directly into sausage or other processed meats. "Since the Meat Act of 1906 we have never prohibited brain or spinal cord," she said. "It is part of the animal. However, it is not something people expect to find in meat. Therefore, as of May of last year, we have told our inspectors that if they suspect brain or spinal cord of getting into meat, they should report it." The inspectors' union expressed concern that it would be difficult for its members, already bogged down in other duties, to take on this additional task. The agency employs 7,535 inspectors in 6,200 meat and poultry slaughtering and processing plants. To date fifty-four reports have been filed and five plants have been found in violation of the rule. '

'The Rocky Mountain Laboratories is an unassuming NIH outpost hunkered in the shadow of the magnificent snow-crested Bitterroot Mountains. Built on a residential street in Hamilton, Montana, the red-brick structure stands out like a Brooks Brothers suit on Casual Friday. The lab was set up by the state in 1928 to study Rocky Mountain spotted fever, a deadly tick-borne disease that plagued the region. The people of Hamilton were so nervous about ticks going AWOL from the lab that a moat -- really, a puddle-deep trench -- was dug around its perimeter. Over time the laboratory has branched out to consider a wide range of infectious diseases, and has attracted, among other notables, a world-renowned team of experts on TSE. One of these is Byron Caughey, a strapping, bearded biochemist who looks nothing like the poet whose name he shares.'

US food supplements questioned

Correspondent opinion: Terry S. Singeltary Sr.  1 Sept 98
"Thought you would want to know, I was in the store this morning (little fast food, stop n go type), by the cash register, where you always see the rack of SUPER DUPER VITAMINS for sale in a package (I can't ever pass a bottle of pack of vitamins, without reading the ingrediants), when LOW AND BEHOLD, there was MADCOW PILL FACING ME RIGHT IN THE EYE, FRESH START; 1-800-727-1226."

"They have several different packages, under the GREAT START INGREDIANTS, amongst all the vitamins and minerals, you find, DESICCATED LIVER, made from ARGENTINA BEEF LIVER. NEXT, under the ULTRA START, INGREDIANTS, RAW GLANDULAR COMPLEX 500, LIVER, SPLEEN, KIDNEY, PANCREAS, DUODENUM, HEART, THYMUS, ADRENAL, PITUITARY, AND "B R A I N"! When I called them, they didn't have to much to say, (WHAT THE HELL COULD THEY SAY!). "

Meat industry fears controls after warning from scientist

September 8 1998  Michael Hornsby The Tlimes
Europe to check on lamb safety after BSE claim

EUROPEAN Union scientists are to re-examine the safety of lamb after a British expert advising the Government said it was "a distinct possibility" that "mad cow" disease had passed into sheep. Franz Fischler, the European Agriculture Commissioner, is also to resubmit proposals to ban high-risk parts of sheep from the food chain. Britain already has such measures in place, but most EU countries have considered them unnecessary.

The flare-up of concern over BSE in sheep came at the worst possible time for the food industry in Britain, where the Meat and Livestock Commission yesterday began a 2 million campaign to promote lamb consumption.

Colin Maclean, director-general of the commission, said there was nothing new in the latest reports and insisted that the public was fully protected against potential risks by existing safeguards.

"The Government's expert committee on BSE has on three separate occasions examined the theoretical risk of BSE occurring in sheep and at its last meeting concluded that no further action was needed to protect the public," he said.

Ben Gill, president of the National Farmers' Union said: "It is essential to remember that not a single case of BSE has ever been found in a commercial flock. Meat and bonemeal, the suggested source of BSE, has not been fed to sheep since 1988. The amount fed to sheep was always far less than to cattle and any sheep that did eat it would have been slaughtered long ago."

Roger Reeson, managing director of Dewhurst, which has about 200 butchers' shops, said: "Lamb sales significantly increase at this time of year, which is the peak of the season, so, with the best-quality lamb in the shops now, the last thing we expect is a downturn in sales."

The Consumers' Association said the Government had failed to put the risk to consumers in context. "When we became aware that BSE might have got into sheep, we wrote to the Department of Health asking for advice, for example on whether babies should be fed lamb, but we did not get any coherent answer," said Sheila McKechnie, director of the association.

Sir Kenneth Calman, the Chief Medical Officer, said last night that the Government's Spongiform Encephalopathy Advisory Committee (Seac) had advised that "there was no new evidence and no grounds at this stage for thinking that the likelihood of BSE in sheep is any greater now than in the past" and that no further action to protect public or animal health was necessary.

The Department of Health said it accepted that parents would be concerned. "However, infants and children are not likely to be more susceptible to BSE infection than adults."

The flurry of statements came in response to remarks by Jeffrey Almond, Professor of Microbiology at Reading University, who chairs a sheep sub-group set by Seac to co-ordinate research. He said: "I think there is a distinct possibility that BSE is out there in the sheep population. If we found BSE in sheep it would be a national emergency.

"The politicians would have to live with the possibility that, if they went down the road of stopping the consumption of sheepmeat, that would be 40 million animals to be destroyed, a whole industry collapsing and the consequent cost to the nation of that."

What Professor Almond is saying is not essentially new. Seac advised the Government two years ago of the risk that BSE might have passed into sheep and be disguised as scrapie, which is not harmful to human beings. Last month it called on the Government to fund extra research.

The main difficulty is that strain-typing tests to show whether an infected sheep is suffering from scrapie or BSE cost 30,000 each and take up to two years to produce results. Only nine have so far been conducted.

John Collinge, head of neurogenetics at Imperial College School of Medicine in London, also a member of Seac, said: "We need now to scale up our tests to screen thousands of animals. There are quicker and cheaper ways of doing this."

Questions and answers:

Is BSE in sheep?

Nobody knows for sure. Scientists on the Spongiform Encephalopathy Advisory Committee (SEAC) warned the Government two years ago that there was a possibility that this had happened. So far no "mad cow" disease has been found in Britain's 40 million sheep but as yet no great effort has been made to look for it.

How could BSE have got into sheep?

Laboratory tests have shown that BSE can be passed to sheep by deliberate infection. In the field, the most plausible route would be via meat and bone meal derived from the remains of BSE-infected cattle. This could mean that BSE first went to cattle in meat and bone meal from scrapie-infected sheep and then passed back to sheep. But meat and bone meal has been banned as feed for both cattle and sheep since 1988 and sheep were never fed much of it anyway.

If BSE is in sheep, can it infect people?

It is possible that BSE in sheep would behave no differently from scrapie, which has been around for centuries without causing harm. But SEAC takes the view that if BSE were found in sheep, it would have to be assumed to be a danger to humans, in the same way as BSE in cattle. Since 1995 a total of 27 people have died from new-variant Creutzfeldt-Jakob disease, a fatal brain condition linked to eating contaminated beef.

Is it safe to eat lamb now ?

No 100 per cent guarantee can be given. But SEAC thinks the measures in force are enough to protect public health. Any risk, if it existed, is likely to have been in the past and any added danger in continuing to eat lamb is considered to be minuscule. The heads and spleens of sheep of any age, and the spinal cords of sheep over one year old are banned for human consumption, as is meat recovered from the vertebral column of any sheep. Lamb from New Zealand, which has no scrapie or BSE, must be completely safe. Lamb from organic farms, which banned meat and bone meal as feed six years earlier than other farms, is probably the next safest.

Should lamb be fed to infants who have not eaten it before?

The official view of SEAC and the Department of Health is that neither infants nor older children are likely to be any more susceptible to BSE than adults. But both accept that parents may wish to reduce risks for their children "below the level they would accept for themselves".

How can BSE be detected in sheep ?

With difficulty, as it would look the same as scrapie. Traditional "strain-typing" tests involve injecting infected tissue from sheep into the brains of mice and seeing if the resulting damage resembles that caused by BSE tissue. Such tests cost 30,000 each and take up to two years. It is not practicable to test tissue from thousands of animals in this way. It may be possible to screen fairly large numbers of sheep quite quickly by other techiques already used to detect the new strain of CJD in humans. SEAC is expected to recommend soon that these should be tried on sheep, but it is not certain how effective they will be.One solution might be to use these techniques to identify suspect cases which could then be double checked by the more laborious strain typing methods.

How much scrapie is there in sheep?

Information is unreliable. It has been a notifiable disease only since 1993, when 328 cases were reported, followed by 235 in 1994, 254 in 1995, 453 in 1996, 465 in 1997 and 175 so far this year. But there may be much under-reporting. Compulsory slaughter of scrapie-infected sheep, with compensation, was introduced only two months ago. Just over 80 suspect animals have been offered for slaughter since then. If BSE had got into sheep, scientists would have expected to see a dramatic surge in reports of scrapie. This does not appear to have happened.

What should be done if BSE is confirmed in sheep?

Jeff Almond, a SEAC member, says the Government would face "a national emergency" and be forced to contemplate slaughtering all flocks with a history of scrapie or even all 40 million sheep in the country. The problem is that scrapie infection is more widespread in a sheep carcass, appearing, for example, in the lymph nodes, than BSE is in cattle. This might also hold true for BSE in sheep. Simply removing the most dangerous carcass parts at the abattoir might thus not be a sufficient safeguard. BSE may also be able to spread from animal to animal in sheep, in a way it does not do in cattle, making it much harder to eradicate the disease.

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