Volume 2: Science
7. Conclusions drawn from the scientific response to BSE
Policies on research management and evaluation
Funding
Planning and coordination

7.40 We have not undertaken a critical examination of the programme of scientific research carried out by MAFF and the Research Councils. Nevertheless, our consideration of the use of research in response to BSE has been sufficient to identify a number of lessons to be learnt about the management and evaluation of research. We discuss them in this section. We are conscious that there have been many changes in the period since 20 March 1996. It is the task of others to evaluate the extent to which those changes address the matters we have identified. In doing so, and in dealing with similar situations in the future, they should not lose sight of these lessons from the BSE story.

Funding

7.41 We deal first with a common misconception, namely that necessary research into BSE was not carried out because the Government would not provide money to fund it. For most of the necessary research, we did not find any evidence to support this: when additional funding was not forthcoming from the Treasury, resources were diverted from other non-BSE projects. We identify below the small number of areas where lack of, or delay in providing, funds played a real part in delaying necessary research. For the most part delay occurred because of the protracted procedures for obtaining funds, not because they were refused.

Before the bid for supplementary funds was rejected

7.42 A striking feature was the lengthy process of actually bidding for funding. We describe in Chapter 6 the PES system for planning government expenditure. This system required Departments to work to a strict annual cycle for seeking funds for research as for other expenditure. Bids covering three years were submitted in the spring, and, following a series of negotiations, the Department's share of the overall public expenditure was fixed in the autumn by the Cabinet. The detailed Estimates of spending for the next financial year were then presented to Parliament in the spring. If a need for further spending arose during the financial year, the Treasury expected Departments to meet the need by switching resources from other budgets, where possible. If this search proved impracticable, Departments might approach the Treasury for extra resources from the Reserve, but this was regarded as a last resort. The Reserve was rightly kept back by the Treasury for real emergencies. Bids made earlier in the year were less likely to be successful, given that Departments would more readily be able to switch funds from other budgets.

7.43 It was via these procedures that MAFF had to obtain additional funds for its BSE R&D programme. Chapter 6 describes the protracted sequence of events leading eventually to a bid for funds from the Reserve in August 1989, and for strategic funds for R&D in the PES round. This process had taken some two years, involving consultation and drafting and redrafting of submissions and project proposals. An added complication was the involvement of the Southwood Working Party and Tyrrell Committee, and the need for their recommendations to be taken into account in the process. Mr Bradley was clearly frustrated in December 1988 by the 'prelude of time-consuming administrative procedures' which he said was causing progress to stagnate. There had been little progress six months later, when Mr Bradley again expressed his frustration, this time in a minute to the CVO:

. . . If we are to succeed in cracking 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 . . .

. . . 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. ¹

7.44 It is to the credit of those involved that the research programme was not simply halted by this process. As is clear from Chapter 6, research was funded by diverting resources from other projects during this period, despite the cuts that were prevalent at the time. Mr Bradley's updated programme paper at the end of 1988 also demonstrated that in many cases projects had been held up not through lack of funds, but for other reasons. For instance, some awaited the establishment of a suitable animal model - the first stage of which was achieved only in September 1988 with the transmission of BSE to mice.

7.45 However, it was clear that one project in particular did suffer during this period from lack of funds: the maternal transmission study. As we describe in detail in Chapter 6, the importance of ascertaining whether BSE was transmitted vertically from dam to calf was recognised at an early stage. It was identified in the CVO's submission to Mr Thompson in June 1988, and its importance was confirmed repeatedly by, among others, the Southwood Working Party, the Tyrrell Committee, Dr Kimberlin, Dr Ridley and senior officials. Yet there was a considerable delay before the study was finally initiated in August 1989. Although the offspring of affected cattle had been identified and monitored before then, for the reasons Mr Meldrum gave Professor Bell on 31 May 1989, this was not a satisfactory alternative to MAFF acquiring and monitoring the animals. It seemed to us that the principal reason for this delay was lack of funds, coupled with the protracted process of actually bidding for funding. When the go-ahead was finally given for the project in June 1989, it was not as a result of a successful bid for additional funds from the Treasury, but because Professor Bell had found a way of deferring some of the costs, and because the remainder were to be underwritten as an interim measure from within the SVS budget.

7.46 The consequence, it seemed to us, was a delay of some months in acquiring the animals and initiating the study proper.

7.47 Our understanding is that the Chief Scientist's 'special fund' could not be used to fund in-house research, and thus could not have been used in this case. ² However, this episode illustrated to us the tremendous value in having available a small strategic fund that could have been used in such circumstances.

Effect of rejection of bid for funds

7.48 As described in Chapter 6, the bid for funds from the Reserve made in August 1989 was rejected: it was thought that the necessary funds could be found within MAFF's overall research budget. As a result of PES negotiations in the autumn, the bid for strategic funds for BSE R&D was withdrawn, although there was some uprating of funding for externally commissioned research.

7.49 We asked a number of those involved what the effect of this failure to obtain additional funds was. Dr Shannon told us:

I think we were severely disappointed that this bid was rejected, but I suppose we picked up the pieces and tried to get on and put as much work in place as possible. ³

7.50 We also explored the question with Dr Watson and Mr Bradley. When we asked Mr Bradley whether there were other experiments, besides the maternal transmission study, that they were unable to progress because of the funding difficulties, he said:

I do not think in a specific nature like this one because this one was a very expensive study and it was a big decision to go ahead or not. The other experiments, for reasons we have explained previously, due to lack of resource, lack of funding, there were potentially degrees of delay but I do not think significantly so compared with the position at this particular time. As it turned out, in the shortness of time, we did get the experiment under way and very little was actually lost. ⁴

7.51 Mr Bradley thought that lack of funding was one of the constraints on tissue infectivity studies using mice:

. . . when the studies into mice to which Dr Watson refers were initiated, we had a whole range of tissues which we wished to inoculate into mice and which were scientifically sensible, we thought. And obviously multiple sources for each of these tissues as well. And yet we were subsequently rationed to inoculating 30 tissues in one year, 30 in the next and 20 in the final year. Had we had more funding and there had been more resource available, admittedly that work was done without the CVL, done at NPU, it would have progressed quicker. ⁵

7.52 Dr Watson was asked whether studies using hamsters, cattle and pigs carried out at the CVL could have been started earlier if the funding had been available:

There were other constraints in all of this, and accommodation was one in particular, particularly with cattle experiments. We did, I think, utilise funds from other sources and staff and so on to carry out the transmission work that we had planned. It is very, very difficult to say what part funding or lack of funding played in some of this, to be frank . . .

. . . If one is looking you know into the crystal ball and how funding might have helped the situation in the longer term, I am sure that, you know, one could have been thinking of more high security cattle accommodation. This was a major lack in the research institute. Pirbright had it for foot and mouth, it was tied up; Compton had it, it was tied up with work there on BVD. And ours was limited, it was not fully satisfactory. ⁶

7.53 However, he said that a bid for cattle accommodation was not made at that time:

. . . I do not think so, because we had already committed and were completing a major capital expenditure programme for small animal accommodation. . . We used a major tranche of capital allowance for this accommodation, but to be honest I do not think we had put forward plans for additional cattle accommodation at that time because we were relying for transmission work heavily on the NPU and mouse inoculation, which had been agreed at a meeting chaired by the CVO in November 1988, I think the allocation of work between the two institutes, collaborating institutes. ⁷

7.54 With more funding doubtless more could have been done more quickly. The position was of course different after a link between BSE and vCJD had been announced. Dr MacOwan pointed out:

Post 1996, however, there was a need to expand the BSE programme rapidly after the link to nvCJD was announced. This diverted much of the funding to the necessary investment in the research infrastructure to accommodate the additional projects before the projects themselves could begin. This related to many aspects of the overall programme but notably substantial funds were allocated to pay for the building of large animal accommodation. I understand that the spend on this and other capital items was a total of over £40 million. Prior to the announcement of the link between BSE and nvCJD it would have been impossible to obtain funds of this magnitude for research on BSE. ⁸

7.55 However, notwithstanding that funds were more limited, with the exception of the delays in the maternal transmission studies, it did not seem to us that the carrying out of research into BSE that had been identified as necessary was prevented by lack of funding. As Dr MacOwan said:

While [the refusal of extra funding in 1989] did not deter MAFF from funding BSE research, it did mean it was necessary to free up funds from other commitments and to recruit and train new staff in a field where expertise was scarce worldwide. The gradual build up of the BSE research spend was initially concentrated on the high priority projects recommended by the Tyrrell Research Consultative Committee. As a result projects given lower priority by the Tyrrell Consultative Committee and possibly research subsequently identified as necessary did not receive immediate funding. It was recognised by all concerned that there were limited resources available and that the projects had to be dealt with in order of priority. ⁹

The background of cuts in research funding

7.56 The background of cuts in research budgets prior to the emergence of BSE, described in Chapter 6, played a part in determining the resources and infrastructure in place to enable research into BSE to be carried out when the disease emerged. 'Resources' went beyond funding per se - as alluded to by Mr Bradley when he spoke about constraints on the tissue infectivity studies - and included skilled staff, for example. Professor Bell explained:

. . . you had to make use of existing people. You cannot suddenly produce people who are experts in this kind of thing. ¹⁰

7.57 His successor, Dr Bunyan, made the same point:

. . . you cannot manufacture expertise, it has to grow. ¹¹

7.58 Animal accommodation was another resource affected by limited funds. We note Dr MacOwan's description of the expenditure on new animal accommodation and capital items when more funds became available after March 1996.

7.59 We also note in this context the relatively precarious position of the NPU prior to and during the BSE period, as a result of pressure to reduce overheads. We consider it to have been extremely fortunate that this centre of expertise was available throughout the period.

Planning and coordination

7.60 Chapter 6 illustrates that the majority of BSE research was carried out in-house by the CVL, and was not subjected to open competition or peer review. Moreover, not only did the CVL perform the role of the contractor, but also its views in large measure determined the research that was undertaken.

7.61 Had the necessary research fallen principally within the province of DH, a very different approach would have been adopted. The research needed would have been identified by DH in conjunction with the MRC, and would then have been put out to contract to whichever contractor appeared best able to provide it, through projects subjected to external peer review. An open call for proposals has the advantage that scientists working in diverse areas may identify a wider range of potential avenues of investigation.

7.62 With hindsight, such an arrangement might have proved preferable in the case of research into BSE.

7.63 An alternative approach would have been to subject the research programme to the overview of an independent research 'supremo' or committee whose remit was, in discussion with MAFF and DH, to coordinate the research and to ensure that contracts were awarded, following open competition, to whoever appeared best able to carry it out appropriately. Professor Almond said of such an approach, following the Review of MAFF-funded TSE research in February 1995: 'This would have the advantage that overlap could be avoided and funds could be directed to the best experts in the field. Moreover a longer term strategic view of the need for certain types of research (eg, the development of transgenic animals) could be developed.' ¹²

7.64 There had previously been proposals for a research 'supremo' to coordinate BSE research - we discuss their fate in vol. 11: Scientists after Southwood.

7.65 Had such a system been adopted in the case of the BSE research programme, alternative strategies to address some of the questions and policy needs might have been identified and explored. It is of course a matter of speculation to seek to identify the differences that such an approach might have made, but we draw attention below to some areas which, with hindsight, it strikes us might have benefited from a research supremo or directed research programme:

1. Epidemiology
   We discuss in vol. 3: The Early Years, 1986-88 the early work of the Epidemiology Department of the CVL. Valuable additional work, including sophisticated modelling based on detailed analysis of a wide variety of data on affected cattle, feed and other factors, has been carried out by other groups, notably under Professor Anderson at Oxford University, and Professor Morris at Massey University, New Zealand. Many of the techniques deployed have been developed only during the period since the emergence of BSE. A research supremo or appropriate body might have helped to bring about the involvement of epidemiologists outside the CVL, and facilitate data sharing with them.An important question was whether the epidemic was fuelled by animals slaughtered for human food at a stage when they were incubating the disease. Another question for epidemiologists was to identify the cause of BABs. Related to both these questions was the need to establish the minimum amount of infective material capable of transmitting the disease orally. We discuss the wide-ranging relevance of this issue above, and note here that its importance might have been apparent at an earlier stage to someone charged with directing and overseeing the whole BSE research programme.
2. Diagnosis
   As indicated in Chapter 3, diagnosis of BSE and other TSEs has depended largely on post-mortem histopathological examination of brain and examination for SAFs by electron microscopy. More recently western blotting and ELISA techniques have been developed. Experimental results of a promising ante-mortem test from the USA using capillary electrophoresis immunoassay, to assay the level of PrPSc in white cell concentrates from blood samples, were published in 1999. Similar research has not been carried out in the UK, although investigations into potential biochemical markers in blood and urine have been undertaken at the CVL. There are many uses for simple, cheap and reliable ante- and post-mortem tests for BSE. A reliable blood test for the diagnosis of subclinical BSE would have been extremely valuable in the management of the BSE epidemic, and might have avoided the cull of a very large number of healthy animals after March 1996 under the Over Thirty Months Scheme. A test suitable for screening either ante- or post-mortem could be used (and could have been used) to assess the number of subclinically infected animals, and in particular to ensure that such animals were excluded from the human food chain. In his report on the Review of MAFF-funded TSE research in February 1995, Professor Almond noted the difficulty in this area and the unique problems encountered. ¹³ He thought it 'somewhat disappointing, but perhaps not surprising' that in spite of the significant amount of money being spent (£1.3 million in 1995/96), there had been little progress towards the development of a diagnostic test that could be used in live animals. We note the detailed evaluation of the different approaches to this problem, and the conclusion that some of them were definitely worth pursuing, while the value of others was doubtful. In his comments on the Review, Professor Hueston noted the importance of identifying clearly the policy objectives behind the search for an ante-mortem test. ¹⁴An open call for proposals, and strategic overview and coordination of the research, might have been of benefit in this difficult area. A resource centre, charged with the distribution of BSE-affected brain samples, antibodies and other biological reagents might also have been very helpful.
3. BSE in sheep and scrapie into cattle
   We discuss above the importance both of seeking to confirm experimentally the hypothesis that BSE was caused by transmission of conventional scrapie agent(s) to cattle, and of the unanswered question about whether BSE is endemic in sheep. A strategic overview of the research programme, and of the emerging results, might have prompted earlier consideration of these questions and initiation of appropriate experiments.
4. Sensitivity of mouse bioassay
   We have noted the doubts about the sensitivity of the mouse bioassay expressed as early as 1991. A research supremo might have assisted in initiating a comparative bioassay at the earliest possible opportunity, and in encouraging alternative approaches to infectivity studies, such as the development and use of bovine PrP transgenic mice.
5. Lateral transmission
   It seems to us that more attention might have been given to the investigation of lateral transmission of BSE in cattle following the tentative results of the 1993 case cohort study to which we have referred above. A coordinated study, based on the experiments which successfully demonstrated lateral transmission in sheep in the past, might have been very informative on this issue.

7.66 Finally, a 'supremo' arrangement of this kind would have given more scope for independent scientists to make imaginative proposals.