Volume 2: Science
Part 3: Research into TSEs - a narrative account
MAFF's TSE research
1989
SEAC

1989

The Southwood Working Party's approach to research

6.166 As noted above, the Working Party made interim recommendations in June 1988, one of which was that offspring of BSE-affected cattle should be obtained and monitored (this was referred to as 'the offspring' or the 'maternal transmission' study). On 24 January 1989, comments were requested within MAFF on a draft submission to the Parliamentary Secretary recommending the purchase and retention of 300 such offspring and 300 controls. ¹ The draft submission indicated that the study was being carried out on a voluntary basis, which meant that there would be nothing to stop the owners slaughtering the animals at any stage, without even informing MAFF. If a number of farmers chose to do so during the period of observation, the study would be invalidated.

6.167 The Southwood Working Party presented their report to Ministers on 3 February 1989. In it, they noted that MAFF had identified 300 offspring of affected cows, and they urged that all necessary resources be made available to ensure that these animals were monitored and were not destroyed before they were old enough to display the disease, should they be infected. Otherwise acquisition of knowledge about vertical transmission could be delayed for some years. ²

6.168 The Southwood Report noted that the Working Party's interim recommendation that a committee be set up to advise, coordinate and oversee the research work in this area had been accepted. It also identified areas of research that the Working Party believed should be considered in the fields of epidemiology, transmission, genetic studies, molecular biology and surveillance. As the Working Party noted, many of the recommended studies were already under way or were planned.

6.169 After some discussion, a revised version of the draft submission on the 'offspring' or 'maternal transmission' study was sent to the Parliamentary Secretary on 28 February 1989 by Dr Watson. ³ He emphasised the importance placed on the study by the Southwood Working Party, and recorded that the TSE consultant, Dr Kimberlin, and Dr Rosalind Ridley of the MRC had that morning agreed that it was essential that all the offspring in the cohort were under the complete control of MAFF. The submission estimated the costs of the study at £1.5 million over the full period of 6-7 years.

6.170 The study was one matter considered when the MAFF Permanent Secretary, the CSA, the CVO, Dr Watson and others met on 1 March 1989 to discuss the funding of the proposed new R&D programme. ⁴ They agreed that the study should be commissioned and that MAFF should purchase the whole study group of cattle. Dr Watson agreed to coordinate the preparation of a properly costed research proposition to be put to the new Consultative Committee on Research chaired by Dr Tyrrell, and also of a paper to be put to the Treasury at the same time, indicating the extent to which the study could be funded with existing resources, and the extent to which additional resources would be necessary.

The Tyrrell Committee

6.171 The work of the Tyrrell Committee is discussed in detail in vol. 11: Scientists after Southwood.

6.172 The maternal transmission study was discussed by the Committee at its first meeting, on 13 March 1989. ⁵ It noted that, while a more efficient [and cheaper] design using fewer animals could be put forward, this would be at the price of two years' delay. Dr Tyrrell agreed to circulate urgently a draft letter to the Permanent Secretary on the proposal.

6.173 The Committee also noted at this meeting that it would not consider research applications (although there might be exceptions for work originally it had suggested). ⁶ Individual members of the Committee would be recommended to the funding bodies as referees for relevant grant applications, and a list of these applications would be supplied for information and, if appropriate, comment. Hence, the Committee would not act as peer reviewers.

6.174 Among other general matters discussed were the centres that might be able to assist in fundamental and animal work. ⁷ The Committee noted: 'Factors limiting progress in understanding BSE included not only inadequate financial resources but also shortage of skilled manpower. The bulk of the work would have to remain with CVL and NPU, since no-one else matched the extent of their expertise.' However, certain other centres were identified for specific areas of work. The Committee also noted that since animal epidemiologists were few in number, modellers with more experience in human work might be able to help.

6.175 On 17 March Dr Shannon sent a minute to the Permanent Secretary, Mr Andrews, about the proposed R&D programme for BSE and salmonella. ⁸ His view was that they were not yet ready to make the detailed case for additional funding to the Treasury. There were details to be sorted out with the CVO and ADAS (relating to the reordering of priorities and the funding of the AFRC work at the NPU), and he proposed to hold a meeting to achieve this, and report back. Mr Andrews accepted that they were not yet ready to go to the Treasury, but asked for further advice as soon as possible. ⁹

6.176 Dr Tyrrell wrote to Mr Andrews on 21 March to summarise his Committee's discussion of the proposed maternal transmission experiment. ¹⁰ He noted that transmission from dam to offspring might be detected by carefully recording the development of cases in herds. Alternatively calves might be removed as proposed. The most clear-cut experimental design, he said, would be to separate them shortly after birth and maintain them under close supervision on MAFF premises. However, ensuring that they had not received any suspect feed supplement would restrict the study to calves born after the ruminant feed ban became operative. This would mean about two years' delay in the answer being available, since some of the oldest offspring of affected cattle were now over two years of age. The opportunity to use ADAS experimental husbandry farms to hold the animals might also be lost if not taken up at once. Therefore the trial had been designed to show whether calves available now from affected cows would have a significantly greater incidence of disease than contemporary controls. Consideration had been given to the number of animals (a total of 660) needed to ensure that if there was a low but significant rate of transmission, this would be detected by the study. Dr Tyrrell expressed the hope that his observations would assist Mr Andrews in deciding the form the study would take and how urgently it should be taken forward.

6.177 On 3 May 1989 the Chief Scientist's Group informed Mr Thompson of the programme of BSE (and salmonella) research recommended by its R&D subcommittee. ¹¹ Planning of the maternal transmission experiment continued. ¹² Mr Bradley had been appointed as project leader, ¹³ and on 4 May he noted that once funds were provided - 'and it is important to pay farmers for animals promptly and have funds for feed/veterinary services available at the outset' - it was thought that one month would be needed before the first animals were moved in.

6.178 On learning that the R&D programme would be considered by Ministers before it was submitted to the Treasury, Mr Bradley voiced concern about delays to Mr Meldrum:

CSG advise that even if the submission to Treasury is approved and prompt, funds are unlikely to be available until the Autumn. . . . This further round of bureaucracy will result in more delay especially with the initiation of the offspring experiment which is becoming impossible to defend. May I suggest that you write to Professor Bell indicating both our frustration at repeated preparation of documentation which bears no fruit and the inability to progress important experiments recommended by Professor Southwood (and I anticipate supported by the Tyrrell Committee). If we are to succeed in this disease and provide information for Ministers to make decisions or defend actions, we must short cut the 'red tape' and obtain what we can from the Treasury so the new R&D can begin.

Professor Bell said the offspring experiment cannot begin until funds are available (meeting minutes K C Taylor 7.3.89) but I understand the Management Board said it should go ahead without. This is not only difficult to reconcile but impossible to deliver as farmers and hauliers have to be paid promptly at the start of the experiment. Each delay increases the number of animals becoming pregnant and thus reduces the source number and delays the experimental result. Dr Watson and I commenced preparing information for submission to the Minister on BSE R&D as early as January 1988. It is regrettable that we are still doing the same nearly 18 months later and are unable to progress the offspring experiment, the infectivity studies (via NPU) and new work due to lack of funds and staff. ¹⁴

6.179 On 18 May 1989 Mr Wilesmith sent Mr Bradley a separate proposal for the maternal transmission study, ¹⁵ for formal approval. ¹⁶

6.180 On 26 May Mr Andrews minuted Mr Meldrum about the maternal transmission study. ¹⁷ He said that although he understood the funding problem, they must find the resources to initiate and carry forward the work. Mr Meldrum minuted Professor Bell on the subject expressing his 'extreme concern about the delays'. ¹⁸ He said that progress was 'impossible in the absence of any assurance that funds are available' and that one year had been lost already. The losses were exacerbated by the fact that the study had to be carried out only on non-pregnant and non-lactating animals; and 'the oldest of the offspring and controls will already have been served - and more will be served every month'. Mr Andrews, to whom Mr Meldrum's minute was copied, said that he wanted the work on the study to begin straightaway. He asked for a note from Mr Geoffrey Hollis, Head of MAFF's Financial Planning Division, on how the work would be funded pending the outcome of discussions with the Treasury on financing. ¹⁹

6.181 Mr Andrews held a meeting on 5 June 1989, and asked for two submissions on research funding to be prepared for the Minister. ²⁰ He confirmed this in a note to Professor Bell the next day. The first submission was to go forward the same week, on the immediate problems associated with setting up the maternal transmission experiment, in particular how it was to be financed in the short term before extra funds from the Treasury were obtained. The second, to go forward the following week, was to be a submission enabling the Minister to go to the Chief Secretary of the Treasury seeking supplementary funding in the current financial year and in the next PES for the necessary research into BSE (and salmonella). This was to be based on the earlier submission, circulated by Dr MacOwan, and was to set out why the research was needed, why it was to be carried out in-house, and the implications for other non-BSE work if extra funding was not forthcoming.

6.182 Accordingly, Professor Bell prepared a submission for the Minister on 9 June inviting him to agree to both the initiation of the maternal transmission experiment and the making of a bid to the Treasury for the full funding of the experiment. ²¹ He explained that some of the first year's costs would be deferred to the following year, and that, as an interim measure, the remainder of these costs would be underwritten from within the SVS budget. The Minister agreed on 12 June and Mr Bradley took steps to set the study in hand. ²² Following this approval, things moved quickly: the first animals arrived at the Experimental Husbandry Farm on 19 July 1989 and Mr Bradley reported that the experiment was under way. ²³

Interim Report of the Tyrrell Committee

6.183 Volume 11: Scientists after Southwood describes the recommendations of the Tyrrell Committee in its Interim Report, which was completed in June 1989, and the response of Ministers and officials to them. This process naturally interacted with the work that was already in progress on developing a BSE R&D programme, and obtaining funds for it. Mr Meldrum, for example, noted that the Report did not assist them in coming to a view on which projects should be funded, and suggested that no paper should go to the Treasury seeking additional funding for BSE R&D until the Report had been carefully scrutinised. ²⁴ He suggested a meeting between himself, Dr Shannon, Dr MacOwan, Dr Watson and Professor Bourne. Mr Andrews agreed in principle, although he preferred that the work should be done in-house, that is, without at that stage involving Professor Bourne. He asked that they review which of the Tyrrell recommended projects were in hand, and which were not, and that they advise him urgently.

6.184 The second of the two submissions requested by Mr Andrews on 5 June - a revised submission to the Minister in support of the supplementary bid for funding for the current financial year and the PES bid for 1990/1 and subsequent years - was forwarded by Dr Shannon to Mr Andrews on 20 June. ²⁵ Mr Richard McIvor, Head of MAFF's Finance Guidance Division, to whom the draft submission was copied, made a number of comments on what was needed in the submission to persuade the Treasury to provide the funding. ²⁶ He said that they needed to relate individual R&D projects closely to policy initiatives and to illustrate their preparedness to reassess the worthwhileness of every research project they were currently undertaking.

6.185 The two strands, Dr Shannon's R&D submission of 20 June and the response to the Tyrrell Committee's Interim Report, were brought together by Dr MacOwan in a draft of the urgent advice requested by Mr Andrews, which he circulated for comments on 26 June. ²⁷ This identified work that was in hand, and provided a table aligning the research proposals in the Interim Report with those in Dr Shannon's submission. Following discussions, a revised version was sent to Mr Andrews by Dr Shannon on 30 June 1989. Mr Andrews chaired a meeting to discuss the draft submission on 13 July. It was agreed that a letter should be drafted for the Minister to write to the Secretaries of State for Health and for Education and Science inviting them to agree that they had no choice but to fund as an immediate priority all work given two or three stars by the Tyrrell Committee. ²⁸ Two tables were produced following the meeting - one dealing with MAFF work, and one dealing with work considered the responsibility of other Departments.

6.186 Volume 7: Medicines and Cosmetics describes how these tables dealt with Tyrrell recommendation A1d (investigation into the fate of bovine tissues) and C2a and C2b (transmission studies relevant to pharmaceuticals). Much of the other work recommended by Tyrrell was, according to Dr Shannon, in hand or planned. ²⁹

Bid for supplementary funds from the Treasury

6.187 As described in vol. 11: Scientists after Southwood, Mr Andrews sent the revised submission and draft letter to the new Minister of Agriculture, Fisheries and Food on 28 July, and Mr John Gummer, who had been appointed to that post a few days earlier, duly wrote to the Secretaries of State for Health and for Education and Science. His letter included a draft press announcement about the implementation of research recommended by Tyrrell, but noted that this was contingent upon extra money being available from the Reserve for that year. The letter was copied to the Chief Secretary for the Treasury Reserve, Mr Norman Lamont, and therefore constituted a bid for extra funding.

6.188 Experiment Leaders and others met at the CVL on 28 July, when Dr Watson reported that Mr Andrews had instructed that all projects given two and three stars by the Tyrrell Committee should be initiated immediately. The position at the NPU on project C1a (tissue infectivity studies) was said to be uncertain, and there was a consensus that somebody senior should 'tell the AFRC to progress 2 star and 3 star work'. ³⁰

6.189 Following the meeting, Mr Bradley prepared documents identifying restraints on progress on the recommended research. ³¹ In relation to transmission studies C1a and C1b, he said that it was imperative that this work was initiated forthwith. An approach via senior management to the Permanent Secretary to instruct immediate funding of this work identified as NPU research would, he said, largely solve the problem. If this was not possible, there would be a serious danger of public criticism. Mr Bradley noted that the work could not be undertaken in-house on the scale necessary and in the timescale demanded. Setting up a mouse colony at the CVL was a more expensive alternative. The restraints Mr Bradley identified for these experiments were 'animal accommodation, specialist staffing (animals and pathology), capital equipment for storage of tissues and accommodation for such storage'.

6.190 Mr Meldrum met Dr Watson and Mr Bradley on 7 August 1989 to discuss BSE R&D. He said that no further cuts in non-BSE R&D at the CVL should be made to accommodate BSE work. The new R&D should be initiated and he would take up any shortfall of funding with the Permanent Secretary. There was also discussion of the problems with the tissue infectivity studies, and Dr Watson suggested in a minute to Mr Meldrum the following day that he might wish to consider what advice should be given on how stimulus might be applied to get this moving. ³²

The Treasury rejects the bid

6.191 The Chief Secretary to the Treasury replied to Mr Gummer on 11 August. While agreeing that it was necessary to carry out research into the causes of BSE, he had difficulty with the proposed funding arrangements. In the current year, he felt that the necessary funds could be found within MAFF's overall research budget. He added that the possibility of funding from industry should have been considered, given that it was very unlikely that BSE was transmissible to humans. ³³ Officials had also advised Mr Lamont that it was 'still early in the year to concede a claim on the Reserve'. ³⁴ He wrote a similar letter to Mr MacGregor, since 24 July the new Secretary of State for Education and Science, who had written to Mr Gummer agreeing to his proposed announcement about the Tyrrell Report, subject to funds being made available from the Reserve. ³⁵

6.192 The Treasury did not provide additional funds for the research recommended by the Tyrrell Committee, although they did agree to a modest increase in provision for the external programme. ³⁶ Mr Brian Dickinson, Principal Finance Officer in MAFF, told the Inquiry:

Well, what happened was [the Minister] withdrew the bid for strategic research and development. He withdrew the bid for extra BSE and salmonella research in terms of getting more money for it. But he retained the bid for an uprating of the externally commissioned research generally to take account of cost increases, which I think in particular were the pay increases in Research Councils. So that overall there was an increase in funding, but then out of that resultant amount it was necessary for the Ministry to find whatever we needed to pay for what was clearly the priority, namely BSE and salmonella. That meant crowding out other spending. ³⁷

The Treasury did, however, provide £6.3 million over three years for what became the AFRC's Biology of the Spongiform Encephalopathies Programme (BSEP), which is described briefly later in this chapter.

6.193 On 14 December 1989 Mr Bradley minuted the CVO regarding tissue infectivity studies. ³⁸ He stated that since his last document (9 November 1988) refinements to the list of tissues for potential study were required, resulting from the introduction of the ban on Specified Bovine Offal; extrapolation of data from Hadlow's studies into scrapie in sheep; the requirements of the research programme; additional uses of bovine tissues by the pharmaceutical industry; and additional uses of bovine tissues on farm land, in schools, etc. He noted that mouse transmission studies at the NPU were limited in years one and two to 30 in each, and in year three to 20. Already 13 of the available transmissions for year one were in progress, including semen, placenta, spleen, buffy coat and others. Four more were proposed and approved (liver, udder, pancreas and milk), which left only 13 available for year one. Mr Bradley noted that the tissues of highest priority for transmission studies should be identified and sent to the NPU for inoculation. He attached a draft list for proposed tissues to complete the quota for year one. These were: embryos, uterine flushings, semen, testis, ovary, abomasum, reticulum, rumen, omasum, oesophagus, distal ileum, prefemoral lymph nodes and foetal calf serum. Following consultation, Mr Bradley put forward a revised list of tissues to be inoculated in year one. ³⁹ As vol. 11: Scientists after Southwood notes, all the projects identified by the Tyrrell Committee as being of two- or three-star importance were put in hand.

6.194 The Tyrrell recommendations had included the following epidemiological study:

Survey of brains of cattle routinely sent for slaughter to monitor incidence of unrecognised infection. Although there is no firm evidence for evasion of compulsory notification and slaughter of BSE-suspect cattle, formal study of cattle presented as acceptable for human consumption would provide reassurance and might even reveal spongiform change in animals with atypical or subclinical infection that has not been recognised. ⁴⁰

6.195 However, a number of those closely involved with BSE considered that this project was not worthwhile, because it required substantial resource input while not promising particularly useful results. Mr Meldrum told the Inquiry that the aim of such a study would be 'to monitor the incidence of unrecognised infection and also to provide reassurance that there was no evasion of compulsory notification and slaughter of BSE suspect cattle', but that in his view:

. . . this project would place a very large burden on our over-stretched BSE diagnostic laboratories and I questioned whether it was likely to provide any valuable information that would have any bearing on any possible human health implications of the disease. I placed greater emphasis on veterinary ante-mortem inspection of cattle and the SBO controls to meet the legitimate public health concerns raised in this section of the Tyrrell Committee report. I was also aware that research proposals were in hand to examine a sample of positive and negative bovine brains to ensure that there was no change in the histopathological appearance of the disease. ⁴¹

6.196 The matter was raised by the House of Commons Select Committee on Agriculture during hearings in May and June 1990, one member stating that he could not see 'how epidemiological work of any merit can go ahead without routine sampling of cattle brains which may or may not have scrapie-like disease'. But Dr Pickles of DH, Dr Tyrrell himself and Dr Kimberlin, who each gave evidence to the Committee, were all cautious. Dr Pickles told the Committee:

I think I should explain to do this survey, on the evidence we had available that very, very small numbers of clinically affected animals reach slaughterhouses, the survey would involve not just histology of brains which is fairly quick but would actually involve inoculating brains from animals that looked normal, even brains that looked normal under the microscope, into a large number of mice and then taking it from those mice into more mice. You are doing it on thousands of brains for a very, very small chance of any information that would be of value scientifically. That is an enormous use of resources over a long period of time for very small return which is why, in fact, the rating has now dropped even lower, as the Minister has said. It is not a worthwhile project and does not really provide information on epidemiology. ⁴²

Later she added:

I think it is important to point out we are talking about human resources. There are a limited number of people who have sufficient skills to do this sort of work and it is very important they spend their time on the important topics. ⁴³

6.197 Dr Tyrrell acknowledged that the project presented problems:

. . . if you kill animals as they go through the abattoir and take the brain out, you could look for the changes of spongiform encephalopathy in the brain. This is very laborious. It is not particularly sensitive; it is, in fact, very doubtful whether you would see any until the animal was sick or just about to be sick, and therefore you would consume certainly a very large amount of the very precious resources we have in expert neuropathological skills and what you would probably find would be a large number of negatives. ⁴⁴

6.198 Dr Kimberlin said:

If I may summarise it very simply, in my opinion, the enormous amount of labour that would be involved in manning an operation of this kind is not worth the additional information it would produce. ⁴⁵

6.199 The Committee's report stated that:

Those calling for the random testing of cattle which have been slaughtered without having first shown clinical symptoms argue that such tests would accelerate our understanding of the likely extent of the disease. This form of research was not accorded high priority by the Tyrrell Committee (because of its heavy demand on technical resources), although the Committee did recommend it as having some value. We believe the Minister is correct to adopt the research priorities recommended by the Tyrrell Committee, but trust that he will give due consideration to this proposal when improved diagnostic tests become available. ⁴⁶

6.200 Although there was general scepticism about this project within MAFF at this time, ⁴⁷ the Permanent Secretary, Mr Andrews, was:

. . . uneasy about possible criticism for not pursuing some of the individual lines of research recommended in the Tyrrell Report even though we have good reasons for not doing so. I should be grateful if you would consider whether we should put a short note to Tyrrell reporting on how his Committee's research recommendations are being followed up. This would give us an opportunity of explaining why we are not pursuing a small number of items and getting his endorsement. ⁴⁸

6.201 Mr Meldrum told the Inquiry that the intention at the time had been that charts summarising the position on the Tyrrell Committee's recommendations were to be put to SEAC at their next meeting. ⁴⁹ However, neither this nor any other summary of MAFF's response to the Tyrrell Committee's Interim Report appears to have been tabled at subsequent SEAC meetings.

SEAC

6.202 The Tyrrell Report also recommended that a 'standing mechanism' might be required to oversee the cooperation and coordination of research. ⁵⁰ In the event, this was part of the wider remit given to the Spongiform Encephalopathy Advisory Committee (SEAC), which started work in April 1990. An account of its work and mode of operation is given in vol. 11: Scientists after Southwood.

6.203 The present volume does not set out how the MAFF R&D programme developed from this period onwards. Volume 11 describes the discussions that took place about the coordination of BSE R&D, including the question whether a research supremo should be appointed. Eventually SEAC was asked to oversee and coordinate all publicly funded research on BSE and other spongiform encephalopathies. It produced two interim reports on research, in April 1992 and September 1994 respectively.