Volume 8: Variant CJD
2. History of CJD surveillance up to 1990
BSE discovery and the recommendations for CJD surveillance
Southwood recommendations with respect to CJD surveillance
Government's response to Southwood recommendations with respect to CJD surveillance
Tyrrell recommendations with respect to CJD surveillance

2.21 In December 1986, the Central Veterinary Laboratory (CVL) identified the possible emergence in cattle of a new TSE, later to be known as BSE. ¹ In March 1988, in response to a request from the Ministry of Agriculture, Fisheries and Food (MAFF) for advice on the human health risk, the Department of Health (DH) proposed the formation of a Working Party on BSE chaired by Sir Richard Southwood. The remit of the Southwood Working Party was to 'establish and examine the implications of Bovine Spongiform Encephalopathy (BSE), a newly identified neurological disorder of cattle, in relation to both animal health and any possible human health hazards and to advise the Government on any necessary measures'. ²

2.22 The membership of the Southwood Working Party reflected its concern with both animal and human health and included Sir John Walton ³ who had chaired the MRC's Committee on CJD in the 1970s. ⁴ They met on four occasions between 20 June 1988 and 3 February 1989. (Full details of their deliberations can be found in vol. 4: The Southwood Working Party, 1988-89.)

2.23 The Southwood Working Party discussed the risk that BSE posed to human health. They knew that a link between scrapie in sheep and the human TSE, CJD, had been suggested, but they also knew that there was no evidence to support this suggestion. ⁵ However, they were aware that the agent causing BSE might be a more 'virulent' agent than that causing scrapie, hence the recommendation to destroy carcasses of BSE-affected cattle.

2.24 They considered many points relating to the possible transmission of BSE to humans including:

1. How would it appear and be recognisable?
2. What risk factors might be involved? Would it be occupationally related, or confined to the food chain only?
3. What diseases could it mimic, eg, Alzheimer's, motor neurone disease, and/or multiple sclerosis? ⁶

2.25 The Southwood Working Party felt that 'were transmission to take place then the clinical presentation is likely to be as Creutzfeldt-Jakob Disease' based on what was known about the neuropathology of BSE. This led them to consider the question of CJD surveillance. They were aware of the studies conducted by Professor Matthews ⁷ but they queried how sensitive the present surveillance for CJD was and how readily an increase would be detected. ⁸

Southwood recommendations with respect to CJD surveillance

2.26 On 27 February 1989, the Working Party report was published including their comments on CJD surveillance. ⁹ The report discussed in detail the possible transmission of BSE to man. ¹⁰ It commented that humans were susceptible to some spongiform encephalopathies but that close examination of the evidence suggested that:

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. ¹¹

2.27 However, the Report also stated that it would be a decade or more before complete reassurance of an absence of risk to humans could be given, because of the very long incubation period of TSEs in humans. ¹²

2.28 The Southwood Working Party expressed the view, in paragraph 5.3.6 of their report, that:

It is a reasonable assumption that were BSE to be transmitted to humans, the clinical disorder would closely resemble CJD. Depending upon the route of transmission, the incubation period could be as little as a year (as with some iatrogenic CJD cases) or several decades (as estimated for many natural CJD cases). Identification of any such cases as unusual or atypical would not be easy. However, the Chief Medical Officer could consider whether specialist branches of the medical profession such as neurologists, neurophysiologists and neuropathologists, to whom cases of suspected CJD are referred for diagnosis, should be made aware of the emergence of BSE so that they can report any atypical cases or changing patterns in the incidence of disease. CJD also remains of considerable interest to epidemiologists and they should also be advised to watch for any changing patterns in relation to the disease. The Office of Population Censuses and Surveys is already reviewing deaths attributed to CJD and will be looking for any trend or particular occupation or other characteristics in the deaths certificated to CJD. The question of specific monitoring of population groups considered at enhanced risk of BSE exposure, or more detailed surveys of CJD cases, are included amongst those to be referred to the Consultative Committee on Research. ¹³

Government's response to Southwood recommendations with respect to CJD surveillance

2.29 MAFF and DH announced their response to the Southwood Report on the same day as it was published. ¹⁴ This response included the statement that the Chief Medical Officer (CMO) was ensuring that mechanisms were in place to detect any change in the pattern of CJD, and announced that the Departments intended to set up a Consultative Committee on Research into Spongiform Encephalopathies.

2.30 The CMO, Sir Donald Acheson, wrote on 24 February 1989 to the President of the Association of British Neurologists, Professor David Shaw, enclosing a copy of the Southwood Report. He stated that he would be asking all the neurologists and neurophysiologists for their assistance in monitoring any changes in TSE patterns in man. He also said that the new Consultative Committee on Research, under the chairmanship of Dr David Tyrrell, ¹⁵ would be considering whether more formal monitoring of CJD cases would be appropriate. ¹⁶ Professor Shaw responded on 1 March 1989, offering the cooperation of the Association of British Neurologists. ¹⁷

2.31 On 2 March 1989, Dr Hilary Pickles, Department of Health (DH) secretary to the Southwood Working Party, minuted Sir Donald asking for a steer on a letter she was drafting on his behalf to neurologists and neurophysiologists. In particular, she sought his advice about what neurologists should do in terms of reporting if they believed they had identified an atypical case of CJD. Dr Pickles suggested four options for monitoring any changes reported by neurologists: the Office of Population Censuses and Surveys; the Communicable Disease Surveillance Centre (CDSC); ¹⁸ DH; and an MRC-coordinated surveillance study similar to Professor Matthews's study ten years previously. ¹⁹ She proposed that the 'most satisfactory solution' would be an MRC-coordinated study. Her minute included a handwritten note stating that:

Since writing this I have spoken to Dr Will the neurologist who was involved in the earlier monitoring exercise with CJD and who is on the Tyrrell Committee. He is firmly convinced that only a proper study, with an experienced neurologist deciding which cases can be accepted as true CJD, will give us the information we need. Clinical diagnosis and death certification is potentially misleading in his view.

2.32 Both Sir Donald and Professor Shaw agreed with Dr Pickles that the best way forward for the CJD monitoring was to continue with the system of notification that Professor Matthews had previously instituted. ²⁰ DH also agreed that until the matter of CJD surveillance was discussed with the Tyrrell Consultative Committee on Research and the MRC, the CMO would postpone writing to the neurological network. ²¹

2.33 Sir Donald, in a letter to Professor Shaw, suggested that the reinstitution of surveillance would be a relatively straightforward task, especially as Dr Will, who was a consultant neurologist with experience of working with Professor Matthews on CJD surveillance, was to be included on the Tyrrell Committee, which was to discuss the plans for CJD surveillance:

Would the best way to ensure a continuation of the surveillance of CJD be to invite Dr Will simply to take up Bryan Matthews's mantle if this has not already been passed on to someone else and leave it at that? ²²

2.34 However, Professor Matthews soon highlighted to Professor Shaw the problems that would be encountered in the surveillance of CJD (see paragraphs 2.11-2.16). ²³ Professor Shaw then passed on these comments to Sir Donald. ²⁴ In summary:

1. It was essential that supposed cases were seen by someone (perhaps more than once) with clinical experience.
2. Reliance on death certificates was no help, as 'CJD is written on death certificates in quite a reckless way!'
3. The necessary chasing of pathologists for reports could take up much time. Pathologists were reluctant to perform post-mortems and would be more so after reports of CJD in three neuropathology technicians. There was also the related expense of getting the bodies to willing pathologists.
4. There were potential difficulties in employing a research registrar to do the leg-work for Dr Will. Research registrars would normally expect to produce publications from their work at this stage in their career and this work might not be original enough as several papers had already been written on CJD surveillance.
5. A large budget would be needed to maintain the surveillance for a sufficient period of time, taking into account the long incubation period of human TSEs.

2.35 Sir Donald and Professor Shaw discussed these difficulties and sought advice from Dr Will. ²⁵ The final outcome of their request for advice was that Dr Will presented a paper on his proposals for CJD surveillance at a meeting of the Tyrrell Committee (see below).

Tyrrell recommendations with respect to CJD surveillance

2.36 The Tyrrell Committee met in March, April and May of 1989. The members of this Committee who had experience of CJD surveillance were Dr Tyrrell, the Chairman, and Dr Will.

2.37 Dr Tyrrell had been a member of the Committee on Safety of Medicines (CSM) when it had considered the problems of CJD induced by human growth hormone (see paragraphs 2.17-2.18). He also served as Chairman of the Advisory Committee on Dangerous Pathogens (ACDP), which recommended safe working practices in laboratories handling, amongst other things, TSEs. ²⁶ (See vol. 6: Human Health, 1989-96 for more details on the ACDP.)

2.38 Dr Will was a consultant neurologist at the Western General Hospital in Edinburgh. Between November 1979 and January 1982, he had worked with Professor Matthews on the surveillance of CJD both in England and Wales. ²⁷

2.39 CJD surveillance was discussed at all three meetings of the Tyrrell Committee, and Dr Will presented a paper entitled 'Proposal for the Monitoring of Creutzfeldt-Jakob Disease' ²⁸ at the second meeting in April 1989. ²⁹ Monitoring the incidence of CJD in humans, and instigating a study of relevant occupational groups such as abattoir workers, were suggested but it was also noted that the clinical features of BSE in humans might prove different from sporadic CJD, as had some of the iatrogenic CJD cases. ³⁰

2.40 The Committee approved the proposals in Dr Will's paper and agreed that a surveillance programme should cover all of Britain. It was noted that the programme duration was expected to be lengthy, as it was known that possible analogous human diseases such as kuru had long incubation periods. ³¹

2.41 The Tyrrell Report was presented to the Government on 10 June 1989. Dr Pickles urged her colleagues in DH to arrange the funding for the CJD surveillance programme quickly. She felt that DH should be seen to have research 'on the road' when the Tyrrell Report was finally published and that this programme was the most urgent project for DH. ³²

2.42 On 9 January 1990, the Tyrrell Report was finally published. The Report recommended the monitoring of all UK cases of CJD over the following two decades. It reiterated the view that scrapie was not considered causally linked with CJD but that it was 'urgent that the same reassurance can be given about the lack of effect of BSE on human health.' ³³

2.43 The Report separated the CJD surveillance project into two parts: ³⁴

1. Surveillance of cases of CJD with particular reference to the overall incidence, the geographical distribution, the age and sex distribution, occupational history, association with medication, and any atypical clinical features. This part of the project was rated the highest priority.
2. Prospective monitoring of groups with high exposure to bovine tissues, such as slaughtermen, veterinarians, and regular recipients of medicinal products of bovine origin. This part of the project was rated the lowest priority. As described in subsequent chapters of this volume, this monitoring was not in the event undertaken, as it was considered that the same result could be obtained from an analysis of the occupations of CJD cases.