Volume 11: Scientists after Southwood
2. The Tyrrell Consultative Committee
The maternal transmission study
Origin of the study
The Committee's consideration of the proposed study
Discussion

2.42 The request to the Tyrrell Committee in relation to the maternal transmission study was in effect to peer-review this. As such it fell outside its principal task of advising on the needs and priorities in research on TSEs.

Origin of the study

2.43 Prior to the formation of the Southwood Working Party, MAFF had been monitoring over 300 offspring of cows in which BSE had been confirmed, along with the same number of control animals (offspring of cows not infected with BSE). The Working Party believed it was 'essential that enough offspring of cows known to have had or to have subsequently developed BSE are monitored to enable evidence for or against vertical transmission to be obtained'. They also urged that all necessary resources be used to ensure those animals being monitored were not destroyed before they were old enough to display the disease. ¹

2.44 MAFF's existing monitoring was done with the agreement of the owners of the animals, which meant that the study could be invalidated if the owners decided to slaughter the cattle. While there were a number of options to help ensure the study 'cohort' remained intact, the purchase of animals was the only method by which MAFF could obtain complete control over the cattle concerned. On 24 January 1989 Mr Lawrence of MAFF distributed a draft submission intended for the Parliamentary Secretary to Mr Meldrum, Dr Watson, and Mr Wilesmith, among others. This recommended the purchase of 600 calves (300 offspring of BSE affected animals and 300 controls) for monitoring, followed by slaughter and histopathological examination at four years of age. ²

2.45 On 14 February a joint MAFF and DH meeting was held to discuss the implications of the Southwood Report recommendations. It was agreed that the monitoring of offspring of affected animals was an important point, and it was noted that Mr John MacGregor, the MAFF Minister, had already acknowledged this. MAFF would seek advice from independent experts to ensure that what they were doing was technically sound. Ministers would decide how to proceed once that advice had been received. ³

2.46 Dr Watson subsequently had a meeting with Dr Kimberlin and Dr Rosalind Ridley of the MRC on 28 February 1989, and their 'firm conclusion' was that it was essential that the study cohort be under the complete control of MAFF. They also thought 400 offspring of affected animals and 400 control animals would be required to allow for mortality throughout the duration of the experiment. Dr Watson sent a note to the Permanent Secretary that day, based on Mr Lawrence's draft submission, but also informing him of the conclusions drawn at the meeting held that morning, particularly that it was now thought that 800 animals were required to make the study successful. ⁴

2.47 The next day Mr Andrews met senior MAFF officials and agreed that the proposed study should be commissioned, and that the Ministry should purchase the whole study group of 800 cattle. Dr Watson was to coordinate the preparation of a properly costed research proposition that would set out the scientific design of the experiment, and this would be put to the Tyrrell Committee for comments and advice. ⁵

2.48 The research proposal was prepared by Mr Wilesmith, and was considered at a meeting of MAFF officials on 3 March 1989. ⁶ The objective of the study was to examine maternal transmission under natural conditions, and its main features were:

• the comparison of the incidence of BSE in the offspring of animals confirmed as having the disease (cases) with that in the offspring of unaffected animals (controls);
• cases were defined as female offspring of confirmed BSE-affected animals born six months or less before the onset of clinical signs in their dam or after the onset of clinical signs;
• controls were defined as female offspring of cows in affected herds from which the cases were selected, born in the same calving season as the cases. The dam should have survived to at least six years of age without clinical signs of BSE;
• a sample size of 300 cases and 300 controls (it appears that a late decision was made to settle for this number of animals, which was the statistical minimum required for the study to be successful);
• cases and controls would be purchased and maintained on MAFF or other property; and
• a maximum period of seven years for the experiment. ⁷

The Committee's consideration of the proposed study

2.49 Dr Watson presented Mr Wilesmith's paper to the Tyrrell Committee during its first meeting on 13 March 1989. The minute records that the Committee was told the Minister had already accepted the need for this study, ⁸ so their role was to advise on the most effective way of implementing it. ⁹

2.50 Following its discussion of the proposal, the Committee decided that Dr Tyrrell would write to Mr Andrews outlining its views on the maternal transmission study. ¹⁰ Dr Tyrrell's letter of 21 March 1989 summarised the main points raised by the Committee:

• the clearest experiment would involve separating the calves from their dam shortly after birth and maintaining them under supervision on Ministry premises;
• ensuring that the study cohort received no suspect feed supplements would involve restricting the study to calves born some time after the ruminant feed ban (ie, long enough to allow any residual meat and bone meal (MBM) in animal feed to be withdrawn or used up beforehand), and could delay the experiment by up to two years;
• the opportunity to use the Agricultural Development and Advisory Service (ADAS) experimental husbandry farms to accommodate the study cohort could be lost if not taken up at once; and
• the proposed experiment would therefore run the risk that the calves had been fed contaminated feed, but would still show whether calves from affected dams had significantly more disease incidence than the herd in general. ¹¹

2.51 Mr Wilesmith pointed out later that the Tyrrell Committee's recommendation that calves should be separated from their dam shortly after birth rested on the false assumption that one could tell whether or not the dam had BSE at that time. In only a few cases would the dam exhibit symptoms prior to calving. ¹²

Discussion

2.52 The maternal transmission study has been criticised by Professor Roy Anderson of the University of Oxford as a 'badly designed experiment'. In particular, the decision to proceed with a cohort exposed to contaminated feed was the 'flaw' in the study. ¹³ Members of the Tyrrell Committee agreed that the method employed by the study was not ideal, as indicated in Dr Tyrrell's letter of 21 March 1989 to Mr Andrews (see above).

2.53 Dr Tyrrell explained to the Inquiry that the central issues for the Committee's consideration were how urgent it was to do the experiment, and how important it was that it be refined and precise. The main problem was that if the experiment was undertaken quickly, there was a risk that the calves used would have been exposed to contaminated feed, necessitating the use of a large number of animals to obtain a reliable result. If the experiment was delayed until the risk of contaminated feed had passed, it could produce a clear-cut result with fewer animals. ¹⁴

2.54 The eventual decision to proceed quickly with a large number of animals was based on the need to get information on maternal transmission as soon as possible. In oral evidence Dr Tyrrell said:

Although a clean experiment would have been possible if we had waited until all the contaminated feed was out of the way, it would have meant the answer coming much later. If the answer had been that there was a lot of maternal transmission, it would be better to have that information sooner rather than later. ¹⁵

2.55 The Tyrrell Committee appears to have proceeded on the assumption that if a significantly greater number of cattle born of BSE-infected dams developed BSE than the controls, this would demonstrate that maternal transmission had occurred. They overlooked the fact than an alternative explanation for such a disparity would be a genetic susceptibility to infection from feed inherited by the calves of the BSE dams. This was the most significant weakness in the design of the experiment.

2.56 Whatever the weaknesses in design, however, the Tyrrell Committee rightly concluded that while the experiment was not ideal, it was worth doing. With hindsight, it was as well that the experiment proceeded without delay. Had the experiment been delayed until feed was presumed to be free of ruminant protein, that presumption would subsequently have been confounded when it became apparent that cattle feed had continued to be contaminated by ruminant protein.

2.57 Volume 2: Science can be consulted for an account of the implementation of the maternal transmission experiment, and the results obtained.