Volume 11: Scientists after Southwood
2. The Tyrrell Consultative Committee
The first meeting
Consideration of research identified in the Southwood Report
Views on the Southwood Report

2.26 The first meeting of the Committee was held on 13 March 1989, at the CVL in Weybridge. All members of the Committee attended, as did Dr Levy (the MRC observer) and other representatives from the CVL and NPU.

2.27 Once its role under the terms of reference was established, the Committee considered the actual and proposed programme of research and development by the CVL and NPU, discussed the research areas listed in the Southwood Report (see paragraphs 2.31ff below), and considered the contribution made by bovine ingredients to pharmaceuticals.

2.28 There were a number of presentations of work in progress and planned. Mr John Wilesmith of the CVL's Epidemiology Department outlined his modelling studies thus far. Mr Gerald Wells of the CVL reported on the progress of clinical and neuropathological studies, and his colleague, Mr Michael Dawson, gave a progress report on transmission experiments in calves and hamsters and on one about to be set up in pigs. Dr Hugh Fraser of the NPU presented recent data from transmission experiments in mice, and Dr Watson gave a presentation on the maternal transmission study (see paragraphs 2.42ff below).

2.29 Other items on the agenda included a discussion of which centres might assist in research work, and consideration of a paper on the thermal analysis of DNA and RNA in relation to inactivation of infective agents in food. ¹

2.30 At the end of the meeting it was agreed that Dr Tyrrell, Dr Pickles and Mr Maslin would prepare a draft list of research questions to be considered at the next meeting. ²

Consideration of research identified in the Southwood Report

2.31 During the first meeting Dr Pickles told the Committee that although key research areas had been identified in the Southwood Report, the Working Party had not had time to go into detail. ³ Instead, they listed the following areas of research which they thought the Consultative Committee should consider in detail:

• epidemiological studies - in particular to examine further the role of meat and bone meal as the source of BSE and to determine whether maternal and horizontal transmission could take place;
• transmission studies in a variety of possible host species;
• transmission experiments using muscle and milk;
• the formal monitoring of the health of pigs and domestic pets, with possible transmission studies;
• studies to determine whether the BSE agent was identical in its molecular structure to scrapie, and to determine whether there were single or multiple strains;
• the determination of the nature of the infectious agent;
• studies to determine whether genetic factors were involved in the incidence of the disease in cattle; and
• the surveillance of humans at particular risk, and formal monitoring of CJD cases. ⁴

2.32 The Tyrrell Committee undertook a wide-ranging discussion covering all of these research areas at the meeting. It concluded that in relation to animal epidemiology it 'felt the need for access to supporting data and a detailed presentation from Mr Wilesmith' (see paragraphs 2.60-2.61 below). The epidemiology would then need to be reassessed in the light of the new information. Other questions that would need to be addressed included:

• why there were geographical differences in incidence of the disease;
• whether the scrapie agent had changed and, if so, whether that change was before or after it had crossed the species barrier; and
• whether BSE was already a transmissible disease in cattle and whether it would become endemic in cattle.

Views on the Southwood Report

2.33 Although the members of the Committee agreed that the Southwood Report was a good document, and was a fair reflection of the state of the BSE epidemic, their evidence suggests that they did not treat it as infallible. Dr Kimberlin, for example, said:

I think what Southwood did in the short space of time that he had available to him was admirable, and he did the obvious easy things, and that was fine. But it became very clear to some of us anyway that that would not be enough. ⁵

2.34 The following paragraphs consider particular conclusions in the Southwood Report that were questioned by Tyrrell Committee members.

Human health concerns

2.35 The Southwood Report had concluded that:

From present evidence, it is likely that cattle will prove to be a 'dead-end host' for the disease agent and most unlikely that BSE will have any implications for human health. Nevertheless, if our assessments of these likelihoods are incorrect, the implications would be extremely serious. ⁶

2.36 The term 'dead-end host' has caused some confusion. Volume 4: The Southwood Working Party, 1988-89 discusses the Working Party's use of this term. It is apparent that they took it to mean that BSE would not be naturally transmitted between cattle to a degree to make the disease endemic. They did not, however, discount the possibility that maternal transmission could occur. While Tyrrell Committee members did not dispute the 'dead-end host' conclusion, Dr Kimberlin referred to the Working Party's proviso that, if their assumptions were incorrect, the implications for human health would be very serious, and suggested that it weighed heavily on the Tyrrell Committee members' minds:

This concern about BSE not being a dead-end infection, that it might possibly become a naturally endemic infection in cattle, not only had tremendous implications to animal health, the future of the epidemic, but it had implications to public health, because if the disease was not going to go away, then it would obviously present much more of a public health problem than if it were to go away in due course. So the two things are extremely important, and I think were of major significance to us in focusing on quite a lot of the research programme, to anticipate that. ⁷

2.37 It is apparent that, like the Southwood Working Party, Tyrrell Committee members did not discount the possibility of maternal transmission. At the time Dr Watson felt that the placenta as a route of infection was very likely, ⁸ and Professor Bourne believed it was assumed that maternal transmission would occur. ⁹

2.38 During oral evidence Dr Kimberlin expressed further reservations about the Southwood Report. He referred to the 'enormous difficulty' the Southwood Working Party had encountered in making projections of the number of cases of BSE there would be, and said the Tyrrell Committee was aware that the epidemic was going to be bigger than the Southwood Report anticipated. This was because the Southwood Working Party had based their assessment on constant exposure to infective material, while the Tyrrell Committee knew that there was recycling of bovine material in the food chain, so that it was impossible to make accurate predictions of the number of cases. This realisation raised questions as to whether the Southwood recommendations were an adequate response to the public health issues. ¹⁰

2.39 Dr Tyrrell endorsed Dr Kimberlin's comments, and added that he was concerned about how the Southwood Report had dealt with public health issues in relation to subclinically affected animals. ¹¹ In particular he told us that, in relation to the Report, he:

. . . would have given more emphasis to the probable large numbers of [subclinically] infected cattle which would be by now around, and what we were going to do about them, and something ought to be done, because that is where risks for the human population would mainly arise. ¹²

Scrapie as the origin of BSE

2.40 The Southwood Report had concluded that scrapie in sheep was the origin of the BSE epidemic. ¹³ This conclusion provided an element of reassurance to Tyrrell Committee members that BSE would not transmit to humans, since it was known then that scrapie was not transmissible to humans. However, it did not mean there was no problem. Dr Kimberlin summarised the situation as follows:

There definitely was some good scientific data that said that sometimes, when you cross a species barrier, you create a situation in which the agent will change. You actually exercise or impose a selective pressure, the consequence of which is that the agent can change. So the ethos of scrapie not being transmissible to man that we knew about, and BSE probably having a scrapie origin, did give grounds for optimism, but by itself, it really was not enough to say that there would be no problem from BSE. ¹⁴

2.41 The fact that the scrapie agent had infected cattle suggested that it was possible that it could infect humans also. Dr Tyrrell told us that the Committee treated this threat as a 'distinct possibility and not just a hypothetical idea'. ¹⁵ Professor Bourne likewise commented that although the assumption that a scrapie agent was the origin of BSE was important, 'no one working in this field would ever suggest that BSE could not transmit to man'. ¹⁶