A sorry tale of BSE blunders

November 2, 2001

Even before the botched experiment on BSE in sheep made the news, shortcomings in Maff's studies of BSE had been pointed out by Malcolm Ferguson-Smith, who thinks the government should change how its research is done.

In 1990, it became evident that there was a possibility that BSE might have infected the national sheep flock. It had been found that very small oral doses (0.5g) of BSE-infected material given to sheep experimentally caused disease. The need for research into the possibility that this had occurred naturally was clear.

The main concern today is not whether BSE had been transmitted by meat and bone meal to sheep at the time when cattle were first infected, but whether BSE is present in the national flock. There is substantial evidence that the related prion disease scrapie is perpetuated by transmission from ewe to lamb. While maternal transmission of BSE in cattle is not believed to occur in sufficient numbers to maintain the disease, the same may not be true for BSE in sheep.

The experiment to determine whether the sheep flock had been infected was initiated only in 1995, and it did not begin until two years later (see volume 2, section 3.233, page 123 of the report of the BSE inquiry). It was badly designed. The sample pooled from nearly 3,000 scrapie-infected sheep heads used had been collected previously for a separate experiment by veterinary investigation centres at the same time as BSE-infected cattle heads were collected, and there was a real possibility for contamination. The experiment had no controls such as sheep from countries that are scrapie free or others deliberately spiked with BSE.

The decision to use pooled samples of scrapie-affected sheep brains was also flawed, as it was known that different strains of the infective agent would compete with one another, and as the testing involved infecting mice with the material, the one most compatible with the mouse genotype would tend to be the one detected. Thus the occurrence of scrapie in the pooled sample might mask BSE.

As it turns out, the pooled sample appears to be positive for BSE (see the response to the report of the BSE inquiry, 2.12, page 11), possibly indicating that sheep were infected with BSE via meat and bone meal. But contamination of the sample with cattle brains during collection cannot be excluded.

There is now even a question about the origin of the original pooled sample of scrapie-affected sheep brains, as DNA testing indicates that the sample contains material derived only from cattle. I presume that the samples sent for investigation of BSE infectivity by the Institute of Animal Health (IAH) and for DNA testing by the Laboratory of the Government Chemist both originated from the Ministry of Agriculture, Fisheries and Food (now the Department for Environment, Food and Rural Affairs). Any errors due to labelling or contamination during storage must be the responsibility of Maff, which collected the sheep brains and was almost the sole repository of BSE-affected cattle material.

There are two possibilities to account for the DNA result - either the original sample sent for testing by the IAH was wrongly labelled, or the sample sent for DNA testing was not from the sample investigated by the IAH. The latter possibility seems more likely as it is understood that the IAH found both sheep material and BSE in the original sample. Either possibility reflects badly on Maff and the Veterinary Laboratories Agency. It also raises the question of the competence of government departments and the IAH to carry out research to the required standard.

We also need to know why experiments to test for the presence of BSE have been based solely on a highly expensive bioassay, which requires large numbers of mice and incubation periods of up to two years. Western blotting, a biochemical technique that can identify the BSE protein, gives results almost immediately, but it has been almost completely neglected for unconvincing reasons. Those who have shown that Western blotting can provide unambiguous evidence of BSE infection should be given the opportunity to test current samples of sheep brain both with and without obvious scrapie; it would be possible to screen many thousands of sheep in this way.

The department's failure to develop the test provides another example of the need for coordination between scientists in Defra and external scientists, such as John Collinge of Imperial College, London, whose group has the necessary competence and who would, I am sure, be prepared to set up and supervise a screening laboratory.

A more serious question arising from the debacle is the need to review the 1972 Rothschild arrangements that dictate how scientific matters of serious public concern are researched by the government. Current arrangements have been shown to be inadequate. It would be much better if all projects were offered for open competition among scientists, including external scientists such as those working in universities and research institutes. All projects should be peer reviewed and the results audited.

A precedent for this approach is provided by the Department of Health, which has a concordat that allows it to contract out much of its research to the Medical Research Council. Funds made available to the DoH can be used for peer-reviewed projects by experienced scientists with proven records.

My review of Maff projects on BSE and related issues during the BSE inquiry identified serious shortcomings in design, outcomes and value for money. I believe Defra would be well advised to consider following the example of DoH in using its substantial financial resources to contract out more of its projects. The government's response to the report of the BSE inquiry, published on September 28 (page 110, paragraph 88), does not go far enough in addressing the inquiry's recommendations on research. This is a serious mistake.

Malcolm Ferguson-Smith was a member of the BSE inquiry and is head of the veterinary cytogenetics research group at Cambridge University. He writes in a personal capacity.

Questions that still hang over BSE research

Peter Cotgreave, Save British Science Society
"Maff/Defra research funding went down every single year, with one tiny blip, from 1986 to the present day. You cannot achieve the level of research needed to tackle an entirely new thing like BSE if you cut funding every year. You cannot do it on the cheap.

The May guidelines of 1997, which were updated in 2000, make it very clear that you have got to go where the best advice is going to come from. It is foolish to assume you will always get the best advice in-house."

Richard Lacey, clinical microbiologist and emeritus professor, University of Leeds
"Even if BSE did appear in sheep, the genetic make-up of sheep would make it unlikely that we would be at risk, as illustrated by sheep scrapie.

The real issue is: what is the prevalence of BSE in cattle in Britain at the moment? What I want to know is why they are not doing regular random testing on cattle brains at death, as is occurring in all other European Union countries."

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