Volume 11: Scientists after Southwood
3. The Tyrrell Report
Discussion

3.20 The recommendation to establish the Consultative Committee on Research (the Tyrrell Committee) was one of the first recommendations made by Sir Richard Southwood, in his letter to Ministers of 20 June 1988. Both he and Sir Donald Acheson had envisaged a joint committee of experts chosen by the MRC and AFRC from among scientists with appropriate experience. This concept was opposed by MAFF, who claimed that the CVL had discovered BSE and was already deeply involved in its investigation, and should therefore take a leading role in the committee and appoint its chairman.

3.21 A compromise was eventually reached between DH and MAFF by October 1988. Sir Donald Acheson's nominee, Dr David Tyrrell, Director of the MRC Common Cold Unit and a distinguished virologist, was confirmed as chairman. Dr William Watson, Director of the CVL, and Professor John Bourne, Director of the Institute for Animal Health, both nominated by MAFF and the second DH nominee, Dr Robert Will, a clinical neurologist and expert in CJD, were duly accepted as members of the Committee. The fifth member to be appointed was Dr Richard Kimberlin, who had recently resigned from directorship of the NPU to become an independent adviser on TSEs. None of the members was actively engaged in scientific research on TSEs, although both Dr Watson and Professor Bourne were in charge of institutions in which such research was ongoing. The composition of the Committee was completed by the appointment of Dr Katherine Levy as MRC observer, and of Dr Hilary Pickles (DH) and Mr John Maslin (MAFF), who formed the secretariat.

3.22 The members of the Committee knew about current work on TSEs and were knowledgeable about the published literature. They did not see a need to organise workshops or seminars on the subject or consult more widely with universities, Research Councils and others to obtain new ideas about research into BSE and related issues. They relied on the suggestion of the Southwood Working Party and their review of ongoing research, largely at the CVL and NPU. This enabled them to proceed with speed. They completed an Interim Report after meeting on three occasions.

3.23 The 47 research projects described in the Interim Report of the Tyrrell Committee were prioritised, and a simple notation was used to indicate whether projects had been completed, were in progress, being planned, or simply suggested. The codes indicated where the work was being done, or where it was recommended that it might be done. The main institutes involved were the CVL and NPU. Three of the five members of the Committee were or had been closely associated with these two institutes. While they recommended that careful peer review be used to ensure quality, they did not seek external expert assistance in recommending projects or organisations to undertake them, or suggest an open call for proposals for unassigned projects.

3.24 We do not believe that it was totally satisfactory that the Committee set up to review research into BSE should have included members connected with institutions that were seeking to be involved in carrying out the majority of the research projects. Their priorities must have made it less easy to approach the task of according priority to the difficult projects with objectivity. They were well placed to argue the merits of the different projects, but we feel that it would have been better if they had not been involved in determining priorities. The independent committee envisaged by Sir Richard Southwood and Sir Donald Acheson would have been in a better position to review the current research work and advise on what further work was needed.

3.25 More generally we would observe that the process of recruitment of scientific advisers by MAFF and DH depended to a large extent on the consideration of individuals known to senior officials within the Departments. No attempt was made to consult more widely, and we believe that this limited the choice available. In such situations a wider range of suitable advisers is to be found within the biological sections of the Royal Society, the Royal College of Physicians, the Royal College of Pathologists, the Research Councils (BBSRC/AFRC and MRC), the Foresight Panels and the Wellcome Trust. The Royal Society has a Sectional Committee structure, which ensures a wide knowledge of top scientists in all scientific disciplines. The Royal Colleges have Scientific Advisory Committees for each speciality within their discipline. The Research Councils and the Wellcome Trust have Specialist Boards responsible for funding most of the research in the UK, and their granting and reporting procedures ensure that they have knowledge about the scientific merit of the research that they fund, including the quality of the investigators. This fund of knowledge about scientists and their work should be available to those charged with appointing scientific advisers to the Government.

3.26 The Committee met for the first time on 13 March 1989 and presented its 'Interim Report' on 10 June. It had set about its task with urgency. In a statement Dr Tyrrell explained to us how the Committee saw its task:

The members of the Committee believed that the role of the Committee was to follow up a specific recommendation of the Southwood Report [IBD2(IBD1 tab 2)] with a further report on research. As part of that, the Committee understood that their role was to identify areas of research which could be undertaken to better understand the nature of TSE's, BSE in particular, and their epidemiology. [Governments departments and research funding agencies would use this information to make policy decisions and develop strategies for research.] The Committee members thought they were expected to very rapidly construct a framework against which research proposals could be considered and produce a graded list of projects.

It is important to recognise that the members believed that they were expected to produce a report quickly and we learned that the expectation was that we would focus on immediate research priorities. ¹

3.27 Further urgency was added by the fact that the joint MRC/AFRC review meeting was scheduled for June 1989, and the Committee understandably believed it important to produce its conclusions on research before that meeting. In the event that meeting was postponed.

3.28 The speed with which the Tyrrell Committee produced its Report was commendable, but it had its drawbacks. The Report did not identify the criteria which had been applied to determine the order of priority of the research projects, nor did it explain the reasoning behind the priorities accorded to the different projects. It was not part of the Tyrrell Committee's remit to consider costs, although it was mindful of the resource implications of some proposals, notably those requiring experiments with cattle. ² Inevitably this meant that individual projects were not ranked on a cost/benefit basis. Had they been, we question whether the very expensive embryo transfer experiment would have received the priority that it did.

3.29 We believe that the Departments which received the Report would have wished to reassess its recommendations having regard to the cost/benefit of each project (see paragraph 3.46 below). This was difficult in the absence of any explanation as to why the Tyrrell Committee had accorded each project its particular priority. In the event, the Government decided to adopt a blanket response of putting in hand all the research in the top two categories of priority.

3.30 Dr Tyrrell gave us examples of the objectives of the research proposals:

(i) controlling the BSE epidemic

(ii) eradicating the BSE epidemic

(iii) protecting public and animal health

(iv) addressing basic scientific questions. ³

3.31 We understand that it was the members of the Committee themselves who formulated these objectives, and they succeeded in identifying a sensible list. We think, however, that it would have been desirable for the Committee to seek some input from those who were to be the 'customers' for whom the research would be carried out - those in MAFF and DH who had to handle the disease and take steps to deal with its implications.

3.32 For example, those who had just introduced the ruminant feed ban might then have told the Committee of their need for a test to identify the presence of ruminant protein in feed - an area of research which did not feature in the Tyrrell Report and which did not receive priority treatment.

3.33 In the same context, the practical importance of identifying the minimum amount of infective material capable of orally transmitting the disease might have been identified. Absence of knowledge about this was a recurrent problem when considering practical issues, eg:

1. Was there any need to address the risk that ruminant feed might be contaminated with feed for non-ruminants?
2. Was it safe to spread (i) MBM, (ii) blood or (iii) slaughterhouse waste on land as fertiliser?

3.34 The Tyrrell Committee did in fact give some consideration to whether it should recommend epidemiological research to attempt to identify just how small a pocket of contaminated material was sufficing to infect cattle through feed. Dr Tyrrell told us:

The members of the Committee were aware of the importance of ascertaining the size of the dose that could transmit BSE by oral ingestion. The members of the Committee had thought about epidemiological calculations of the amount of infective material likely to have been included in a cow's rations.

The Committee could have recommended epidemiological calculations of the amount of infected material likely to have been included in a cow's rations. This approach, however, fails to identify an important part of the question, which is that you are concerned with the concentration of infectivity and not just the amount of infected material. The practical or scientific value of such a calculation would have been severely limited by the large number of unknown factors to which a range of arbitrary values would have had to be assigned. ⁴

3.35 We were not persuaded by this reasoning. It seems to us that from the practical viewpoint the important question was the amount of material that was resulting in transmission of the disease rather than more sophisticated questions of titration.

3.36 Another practical need was a cheap and simple post-mortem test, such as the one that Dr Narang attempted to develop (see Chapter 5 below).

3.37 We mention these matters not by way of criticism but simply to draw attention to some of the consequences of having drawn up that Report under pressure. We consider that the Interim Report was a commendable piece of work in the limited time available.

3.38 The Southwood Working Party had recommended, as important research, the feeding to cattle of scrapie-infected meal in order to confirm that scrapie was indeed the source of BSE. The Tyrrell Report did not explain why this experiment had not been recommended by the Committee. These were the reasons given later:

(i) On 25th October 1988 Dr Watson reported to the Chief Veterinary Officer on evidence that scrapie had been transmitted to cattle in the United States of America. He provided information which had been obtained by one of his colleagues, Dr Wrathall, on a visit to America. On 17th November 1988 a BSE Research and Development meeting with the Chief Veterinary Officer was attended by representatives of MAFF and by Neuropathogenesis Unit scientists. The minutes of that meeting record:

'There was a lower priority for the scrapie to cattle experiment since this had been done in the USA but not published. Professor Bourne stated that it was not anticipated that IAH (NPU) would be conducting experiments in cattle at Skedbush; it was agreed these would be done by CVL.' [YB88/11.17/3.1-3.5 at 3.4-3.5]

(ii) The American study had been carried out, not by oral exposure, but intracerebral injection and the scrapie sources used would not have been representative of the strains of agent present in United Kingdom sheep. Collecting suitable sheep material was a major problem and strain typing methods were not available to show that BSE agent was not present as a contaminant.

(iii) Another obstacle was that the possible influence of the genetic make up on the susceptibility of cattle to these agents was not known. This was an important factor to resolve before attempting some of the further experiments on the transmission of BSE to cattle.

(iv) It was recognised that other experiments were being conducted on cattle at the Central Veterinary Laboratory and would either have to be abandoned or new accommodation would be required. A five-year development plan prepared by Dr Watson for the CVO on 9th September 1988 contained a section on transmission of scrapie to cattle [YB88/9.9/2.1-2.16] although it was noted that it was unlikely the experiment would commence in 1988/89. At this time a complete site redevelopment plan was being prepared for the Central Veterinary Laboratory and additional high security cattle accommodation was a first priority in the proposed construction work.

(v) Since BSE was a problem in cattle it made sense to work initially with the bovine agent in preference to scrapie. Although the origin of disease in cattle was of great scientific interest it was not of fundamental importance to the animal and public heath consequences of BSE. Therefore, it was not given priority by the members of the Committee in the Report [IBD4(IBD1 tab 4)]. ⁵

3.39 We now understand why the Tyrrell Committee did not recommend this experiment, and make no criticism of their decision not to do so. It was, however, unfortunate that they did not explain their reasons at the time. In one sense it was true that the origin of BSE was not of fundamental importance to the animal and public health consequences of BSE. Whatever its origin, there was no guarantee that the virulence of the agent would not change upon transmission to the cow. Nonetheless, the belief that BSE was scrapie in cattle was the reason why many - Sir Donald Acheson is but one example - believed that BSE would be as innocuous as scrapie. In time the obstacles that the Tyrrell Committee saw in the way of the scrapie-to-cattle experiment were diminished. More became known on the question whether the susceptibility of cattle to infection was not influenced by their genetic makeup. Additional accommodation was constructed for cattle experiments. Unfortunately, the desirability of the scrapie-to-cattle experiment was lost sight of, and many continued to think that the scrapie theory was not seriously open to question.

3.40 The Tyrrell Committee rightly described its Report as 'Interim', and saw it as a first step:

. . . a framework that could be used by scientists to develop their own project proposals for research which could then be considered by the various funding bodies, that is MAFF, DoH, AFRC and MRC. ⁶

3.41 It also envisaged that the projects would be peer-reviewed. ⁷ We now turn to see what occurred when, having succeeded in producing a Report within three months, the Committee handed that Report to Ministers.