Volume 11: Scientists after Southwood
4. The Spongiform Encephalopathy Advisory Committee (SEAC)
Deliberations and advice
14. CJD in farmers and young people

14. CJD in farmers and young people

4.590 The surveillance of CJD in the UK, which had been recommended by the Southwood Working Party, led ultimately to the discovery of significant similarities between the clinical presentation of BSE in cattle and a new form of CJD which was occurring in young people ('vCJD'). In this section we will look at the consideration given by SEAC to the emergence of a number of cases of CJD in farmers, which were statistically unlikely and therefore suggested a possible connection with the emergence of BSE. We will then set out the consideration given by SEAC to the later cases of what turned out to be vCJD. For a more detailed description of the work of the CJD Surveillance Unit (CJDSU) in monitoring cases of CJD, refer to vol. 8: Variant CJD (vCJD).

4.591 On 13 August 1992, Dr Calman was informed of a first possible case of CJD in a dairy farmer. ¹ On 21 August 1992, Mr Lowson was copied in on a minute from Mr Murray informing the Secretary of State for Health of a probable case of CJD in a farmer who had a cow with BSE on his farm. ² Mr Maslin reported the news to Mr Soames, the MAFF Parliamentary Under-Secretary (Commons), on the same day. He explained that DH advised that there was nothing to suggest that there was any link between this case of CJD and BSE on the farm. Nevertheless, the full facts of the case would be put to SEAC. ³

4.592 At SEAC's 13th meeting on 15 October 1992, Dr Will reported that a cattle farmer, one of whose animals had been confirmed with BSE in 1989, had developed CJD two years later and had died three months after that. Dr Will conveyed his intention to publish a report of the case, which would probably draw the conclusion that there was no evidence that this was not a chance occurrence of normal disease. He also reported that an analysis of the occupational backgrounds of CJD cases in his study revealed no trend. The minutes of the meeting record that DH would look at what needed to be done to ensure that funding was available for follow-up laboratory studies of this case. The importance of such studies in strain typing the agent was stressed. ⁴

4.593 The case was the subject of a letter by Dr Will which was published in The Lancet on 6 March 1993. It resulted in intense media interest. ⁵ In response, Dr Calman released a statement on 11 March 1993 confirming that beef was still considered safe. An extract from the statement reads:

I wish to emphasise that there is no scientific evidence of a causal link between BSE in cattle and CJD in humans. The Tyrrell Committee have considered the details of this case [of CJD in a farmer] and have advised that this does not alter the advice that has previously been given. ⁶

4.594 At SEAC's 14th meeting on 22 April 1993, Dr Will reported that the CJD study continued to show no link with occupation or diet. ⁷ The possibility that the UK farmer might have drunk milk from a BSE-affected cow was discussed. Given the lack of any evidence from epidemiological or transmission studies that milk transmitted the disease, the Committee took the view that there was no further evidence to suggest that milk was a hazard to animals or man and no further measures were needed to protect human health.

4.595 On 12 July 1993, Dr Calman learned of a second case of CJD in a dairy farmer. SEAC was immediately requested to consider this. ⁸ Mr Kevin Taylor reported this development to the MAFF Minister by a minute dated 19 July 1993. ⁹

4.596 A meeting was convened at short notice for 20 July 1993 at which an ad hoc group from SEAC considered the second case of CJD in a dairy farmer. Dr Will began by confirming that the CJD Surveillance Unit (CJDSU) had learnt two weeks previously that a patient with suspected CJD was a dairy farmer with BSE in his herd. ¹⁰

4.597 A number of possible routes of infection were discussed which were connected with the case's work as a dairy farmer were discussed. It was agreed that Dr Will would write to the farmer's wife to ask:

whether the farmer assisted in calving with BSE animals;

what his system was for dealing with the placentae;

whether he carried out de-budding as well as de-horning;

whether the farmer himself injected the cattle and, if so, what injections were actually used? ¹¹

4.598 In connection with the assessment of risk following the identification of the new case, Dr Will drew attention to the CJDSU's Second Annual Report, which had concluded that 'these figures [relating to the case control study on occupation] did not suggest any significant increase in risk of developing CJD in association with any of the specified occupational groups [including farmers]'. ¹²

4.599 SEAC members considered a fax from Professor Peter Smith, an epidemiologist at the London School of Hygiene and Tropical Medicine, concerning the number of cases of CJD that would be expected in the first five years of the national surveillance scheme. On the basis of the information available, Professor Smith concluded that 'the observation of two cases in workers in dairy farmers with BSE-infected herds is disquieting, but the evidence is insufficient at this stage to draw any definite conclusions'. ¹³

4.600 SEAC members concluded that there was no evidence that inoculation of BSE tissue from affected animals had occurred in this case; that the fact that the illness in the cattle and the patient were incubating together made it very unlikely that there was a connection between the two; and that no conclusions could be drawn from the available statistical information. It was agreed that DH would draw up a statement on the basis of these conclusions and that transmission studies should go ahead on the two cases of CJD in dairy farmers. ¹⁴

4.601 SEAC reconsidered the case of the second dairy farmer at its next full meeting on 7 October 1993. Dr Will brought the Committee up to date with the detail of the case. The minutes of the meeting recorded:

The statistical view is that this [second] case should not cause too much concern, however the scientific meaning of the statistical information was discussed. It was agreed that there was a need to use other occupational groups and other countries as a base-line. Dr Will outlined proposed studies using the CJD material from this case and the previous one. The Committee agreed that biological characterisation of the agent needed to be carried out as a matter of urgency. It was also agreed that if a third case of CJD in a farmer with BSE in their herd occurred, an immediate full Committee meeting would be required. ¹⁵

4.602 At SEAC's 16th meeting on 26 January 1994, the Committee was informed of an alleged case of CJD in a teenage girl. ¹⁶ CJD had not been confirmed and the CJDSU was continuing to monitor the case. Dr Will reported that there were three cases of sporadic CJD in teenagers in the literature. Turning to the incidence of CJD, he reported that there were 28 definite and probable cases of CJD reported to the Unit in 1993, compared with 53 in 1992. The 1993 figure would probably increase slightly because of lags in post-mortems and because death certificates were not yet available for 1993. This drop was therefore consistent with ascertainment bias. ¹⁷ Dr Will also reported that a final funding decision for transmission studies on the brain material from the two dairy farmers with CJD was expected in the first week of February 1994, but there was no money for adding extra patients. ¹⁸

4.603 At the SEAC meeting called at short notice on 25 June 1994 to discuss the result of the pathogenesis experiment, Dr Will presented the annual report of the CJDSU. This showed that the general increase in CJD cases in recent years could be ascribed to more cases in patients aged over 75 and that the likeliest explanation was better ascertainment. Subject to some further work, the case control study showed no occupational risk groups but positive association between CJD and eating lamb, beef, venison, veal, kidney and brain. More detailed statistical analysis to strip out confounding variables left only a higher risk of CJD in those with a lifetime exposure to consumption of veal (to a ratio of 13). Meat puddings that had been a factor in the previous year had dropped out. It had to be emphasised that the numbers were very small. ¹⁹

4.604 At SEAC's meeting on 30 August 1994, Dr Will reported that the transmission studies on the two dairy farmers had not yet started. The facilities at the NPU were not complete and might not be for two to three months. The Committee expressed extreme disappointment at this lack of progress. The draft annual report of the CJDSU was also tabled. ²⁰ A covering note for the draft report from the secretariat asked members to form a view on the significance of the finding that veal eating may be a risk factor for CJD. It explained that DH proposed to publish the report at the earliest opportunity, and that it would be helpful if SEAC could provide a statement of its conclusion which DH could include in a press notice. ²¹

4.605 The overall conclusion of the draft report was that there was no conclusive evidence of any change in CJD that could be attributable to BSE. On the finding of increased risk related to consumption of veal, the draft report concluded:

In the context of the overall findings of the study, it is unlikely that this statistical association is of biological significance and the likeliest explanation for the positive findings in the dietary case-control study is recall bias. ²²

4.606 Members agreed a statement that could be used by DH when the report was published. This noted that evidence so far from the combined study of CJD in the EC had demonstrated no difference in the incidence of CJD in countries with or without BSE. This project would provide important comparative information in assessing any epidemiological changes that might be identified in the UK, including the following:

There is no evidence of space-time clustering of CJD cases and no evidence of links with particular occupations. Analysis of possible dietary links continues but interpretation is difficult. We note that the statistical association between black pudding consumption and CJD in last year's report has not been confirmed in the present analysis. The finding on veal in this year's report should be seen in this context. It does, however, appear worthy of further investigation by the Unit in conjunction with other national CJD surveillance projects within Europe.

We have no further recommendations to make to Government on the basis of the report and remain satisfied with the adequacy of current controls to protect public health in regard to CJD. ²³

4.607 On 19 September 1994, Dr Calman and DH Ministers were informed by Mr Lister of a possible case of CJD in a third farm worker. ²⁴ Mr Eddy wrote to the MAFF Minister on the same day to report that MAFF had just been informed by DH of this possible case.

4.608 A special meeting of SEAC was convened on 13 January 1995 to consider the significance of this third case. Dr Will confirmed that a dairy farm worker aged 54, who had worked on a farm with three reported cases of BSE in the herd, had died from suspected CJD. The man was know to have assisted with calving but never with any operative procedure. He rarely drank unpasteurised milk and never drank milk from BSE-affected animals. It was not known if he had ever eaten cattle feed. ²⁵

4.609 The minutes of the meeting recorded that members were reminded that, after the death of the second dairy farmer in 1993, Professor Smith had advised that if four cases arose in the first five years of the surveillance scheme the possibility of an association which was not due to chance had to be given very serious consideration.

4.610 Dr Sheila Gore of the MRC Biostatistics Unit, Cambridge, said that if the adult incidence of sporadic CJD in the UK was taken as one case per million (the figure used by Professor Smith) and if the same incidence applied to workers on dairy farms with BSE-affected herds, the probability of observing three or more definite CJD cases in such workers in England and Wales in five years was low: four in a thousand. The probability was higher if the calculation was made using the total number of dairy farm workers in England and Wales. However, this was considered to be less relevant as the only reported cases of CJD in dairy farm workers since 1990 had been in lifetime dairy farm workers all with BSE-affected herds. Dr Gore recommended:

the number of dairy farmers should be put on a UK basis;

it should be established whether the figure used for the proportion of herds with one or more cases of BSE applied to the UK or to England and Wales only;

actual CJD incidence figures should be used for 1990 to 1994 rather than the guesstimate of one case per million. ²⁶

4.611 The importance of comparative data with other occupational groups was again stressed. For example, the CJDSU had received reports of three cases of confirmed CJD in priests, but had no priests in the control group. Dr Will presented information on CJD in farmers in other European countries - three cases in France in 1992 and 1993, two of which were dairy farmers, and two cases in dairy farmers in Germany since October 1993. However, he had no information on numbers of dairy farmers in these countries. There were no comparative occupational data on CJD in New Zealand or Australia, although Australia was beginning to collect some data. ²⁷

4.612 The Committee concluded that CJD occurring in three dairy farm workers with BSE in their herds within the first five years of the surveillance study was of concern given the low probability of this happening by chance, although there was no evidence to suggest that these were other than sporadic cases. More information was needed before firmer conclusions could be drawn, and Members recommended that the following work should be undertaken as a matter of priority:

a further statistical analysis comparing the relative risks of developing CJD between farmers and other workers who have contact with animals (such as abattoir workers, veterinary surgeons and butchers) with other occupational groups who have no such contact, for example priests and teachers. It was suggested that a breakdown of these cases would be helpful;

a study of working practices in occupational groups such as farmers, abattoir workers, veterinary surgeons, etc, which could be potential risk factors for transmission of the BSE agent. One suggestion was farmers' contact with dust from cattle feed;

a comparison of the incidence of CJD in farmers in the UK with cases in countries with no, or little, BSE;

brain material from the third farmer should undergo transmission studies in the same way as that from the first and second farmers. ²⁸

4.613 The Committee recommended that additional resources should be found for these studies if necessary. It was further agreed that:

the case did not suggest that there was any need for Government to revise the measures already taken to safeguard public health against occupational and other possible routes of exposure to the BSE agent;

a statement reflecting the Committee's assessment of the situation should be prepared by the secretariat for the Department of Health to use in response to any media enquiries.

any further evidence would be considered at the Committee's next meeting on 10 February. ²⁹

4.614 The statement prepared by the SEAC secretariat stated that the third case of CJD in a dairy farmer had been referred to SEAC. It repeated the Committee's conclusion that no further measures were necessary to safeguard public health. In relation to the Committee's view of the statistical relevance of the case, it stated:

Although it is statistically reasonable that three cases of CJD in farmers could have occurred by chance, the Committee recognised that this is a cause for concern. The Committee therefore recommended that, as a matter of priority, further statistical analysis should be undertaken comparing farmers and other workers who have contact with cattle with other occupational groups who don't.

The Committee also noted that cases of CJD in dairy farmers occur in other European countries where BSE is very rare. It is therefore important that the incidence of CJD in farmers in the UK is compared with these cases before any conclusions are drawn. ³⁰

4.615 On 16 January 1995, Mr Eddy reported to the Minister the outcome of SEAC's meeting. He informed the Minister that further work had been requested to refine the statistics to take account of a number of factors to try to get a more accurate idea of the probability of three cases arising in dairy farmers and farm workers purely by chance. In this regard, he reported that MAFF would be cooperating with the study and providing information on the age distribution of farmers, so that the analysis could take account of the age of farmers rather than that of the whole population. ³¹

4.616 At the 18th meeting of SEAC on 10 February 1995, Dr Will presented preliminary information on the third CJD case in a dairy farm worker. He informed the Committee that familial CJD could still not be ruled out in the third case but that the clinical presentations of the three dairy farmers were all typical of sporadic CJD. ³² Dr Tyrrell again emphasised that transmission studies in mice and strain typing in mice of isolates from the three farmers with CJD must be given the highest priority.

4.617 By the time of SEAC's meeting on 8 September 1995, one case of CJD had been identified in a 19-year-old and had been confirmed and another in a 17-year-old was suspected. In addition, Professor Allen was able to update the Committee on studies of the brain of the third farmer. ³³ In response to the news of the second case of CJD in a teenager, the Committee concluded:

It was the Committee's view that the presentation of CJD in adolescents is exceptional but not without precedent. CJD has occurred in adolescents in other countries which are free from BSE and it would therefore be premature to conclude that its occurrence in a teenager in the UK was indicative of transmission of BSE. The Committee agreed that these cases should be studied in great detail and it should consider whether they had any implications for the cause of management of the disease. ³⁴

4.618 In earlier discussions relating to the third case of CJD in a farmer, Dr Will concluded that the priority cases for study, in order of importance, were the cases of the 19-year-old, the 17-year-old, and the third farmer. Professor Allen questioned why teenagers should be given priority over farmers. Dr Will replied that the youngest case prior to the two teenage cases had been 34 years old. He said:

If BSE were infecting the human population, it could be argued that it would be first seen in a teenager. There were also some atypical features - the pathology was unusual for CJD - whereas with the third farmer the clinical features and pathology were typical of sporadic CJD. ³⁵

4.619 Professor Allen said that the 'real problem' was one of resources and of deciding priorities. The work had 'been compromised by a lack of funding, but this should not be an issue for the NPU to address'. ³⁶ Dr Will commented that the NPU had been very helpful in setting up the first cases but they had made it clear from the outset that they did not wish to be a 'titration centre for CJD'. The Chairman said that obtaining resources was not a matter for the Committee. He was worried about deciding on different priorities ahead of time. It was agreed that the issue would be placed on the agenda for the Committee's next meeting.

4.620 The Committee was also invited to consider a draft of the fourth annual report of the CJDSU. The report noted an increase in the incidence of sporadic CJD in the UK; that there was no evidence of a link between occupational exposure to animals and CJD; and that there were statistical associations between various meats/meat products, the strongest association being with venison - veal was no longer a major dietary risk factor for CJD. ³⁷ The minutes of the meeting record that, broadly speaking, the Committee found the findings reassuring. The Committee concluded that although there had been an increase in the incidence of CJD in 1994, it would be premature to conclude that this indicated any additional risk factor for CJD in the UK as this may be due to increased ascertainment, and the incidence in other countries without BSE was similar or even higher. The Committee agreed that no conclusive evidence existed of any change in the incidence of CJD attributable to BSE. ³⁸

4.621 On 28 September 1995, Mr Eddy reported to the Minister on a fourth probable case of CJD in a farmer. ³⁹ He referred to advice to SEAC in 1993 from Professor Smith of the London School of Hygiene and Tropical Medicine, that if four cases of CJD occurred in farmers over a five-year period, the possibility that the association was not due to chance had to be given very serious consideration. A special meeting of SEAC was therefore to be convened to discuss the case.

4.622 This was held on 4 October 1995. Professor Smith and Dr Simon Cousens of the London School of Hygiene and Tropical Medicine attended this meeting to provide expert epidemiological advice. SEAC advised that it was important to undertake further epidemiological studies to detect any particular risk factors that might be involved. ⁴⁰

4.623 Dr Wight invited members to make a 'fairly clear' statement on how they viewed the significance of a fourth case and to consider what other practical measures might be taken. Dr Tyrrell concluded that although numbers were higher than expected they were still extremely small. It would be irrational to take specific measures at the moment. ⁴¹ A statement was drawn up to be issued by DH which included the following:

The Committee concluded that [the fourth suspect case] was difficult to explain as simply a chance phenomenon . . . There may be other explanations for such an association besides infection with BSE, and the Committee noted that there are no reported cases in other occupational groups such as veterinarians who might be expected to be similarly exposed. They also noted that surveillance of CJD elsewhere in Europe has shown a similar incidence of CJD in farmers, including dairy farmers, in countries with no or very few cases of BSE. They therefore felt that it was important to undertake further epidemiological studies to detect any particular risk factors which might be involved, and reiterated their advice that the UK cases of CJD in cattle farmers and the strain of the agent recovered from them should be covered in greater detail.

The Committee have asked for further work to be done, but have not altered their advice to the Government on the precautions necessary to protect either the public health, including farmers, or animal health. ⁴²

4.624 At the 23rd SEAC meeting on 5 January 1996, Dr Will updated SEAC on the CJD situation. There was discussion of a new CJD suspect, aged 52, who had worked in an abattoir. Professor Smith (now a member of SEAC) calculated that one would expect 0.2 cases over a five-year period in the red meat slaughterhouse industry, and felt it was not possible to come to any conclusions on the basis of this case alone even if CJD were confirmed. Nevertheless, he considered that the number of cases in 'at risk' occupations could not be dismissed. Dr Will reviewed the age distribution of cases. Since 1990, there had been four confirmed cases under 30 and one possible, with a very high chance that two of these were genetic. He was not unduly concerned at the overall number of CJD suspect cases that had occurred in the under 30 age bracket, but found it worrying that all the cases had occurred over a very short period. Professor Collinge was 'extremely worried' at the number of young cases in such a short period, 'which could suggest a link to BSE', and requested that a formal statistical analysis be carried out. The Committee concluded that the situation demanded the continuation of the intensive monitoring of CJD. ⁴³

4.625 SEAC's consideration of the events following the 23rd SEAC meeting is dealt with in detail in vol. 6: Human Health, 1989-1996, ch. 7. We can summarise the story as follows. SEAC met again on 1 February. Further concern was expressed about the cases of CJD in young persons. Five cases of patients under 30 years of age had been confirmed. These had an unusual pathology. Further investigations into their genetic data and into the incidence of young cases abroad needed to be carried out before firm conclusions could be drawn.

4.626 SEAC's discussion was clear indication of a real possibility that a link between BSE and a new variant of CJD might be established. It did not, however, result in any attempt to discuss with SEAC what action, if any, might be desirable if the link were established, nor to contingency planning between or within Departments.

4.627 At SEAC's next meeting on 8 March 1996, the Committee was informed that the CJDSU had concluded that a new variant of CJD had emerged in young people in the UK. Eight or nine possible cases had been identified. SEAC expressed concern at the possibility that this disease was related to BSE. At Dr Calman's request, Professor Pattison attended an inter-departmental meeting on 13 March. There was discussion about additional controls that might be introduced. Professor Pattison was told that if SEAC made a recommendation, the Government was likely to follow it. He asked for guidance on the limits of SEAC's considerations and was told that, while economic considerations were secondary, any recommendation should be balanced. ⁴⁴

4.628 SEAC held an emergency meeting on Saturday 16 March. It agreed to recommend that 'all steps should be taken to ensure that the current SBO ban be enforced completely rigorously', but did not reach any conclusion on the need for further action. In the course of discussion, Professor Almond remarked that 'ultimately a decision on whether a zero or minimal risk was acceptable was a political one'. ⁴⁵ It agreed the following formal advice to Ministers:

This is cause for great concern. On current data . . . the most likely explanation at present is that these cases are linked to exposure to BSE before the introduction of the SBO ban in 1989.

CJD remains a rare disease and it is too early to predict how many further cases, if any, there will be of this new form. The Committee are actively seeking further data from both the UK and abroad to help assess the full significance of the Unit's findings. ⁴⁶

4.629 At a meeting of Cabinet Ministers, chaired by the Prime Minister, SEAC's position was explained as follows:

SEAC themselves were split on what action should be taken. Some were of the view that nothing should be done above and beyond the existing controls. Some were of the view that total eradication was the only answer. Others were of the view that the position the Minister of Agriculture was proposing would be acceptable. No doubt SEAC would produce a common position in due course, but given the differing views of some members of the committee, it might not be acceptable to rest on that.

4.630 Professor Pattison was invited to a further meeting of Ministers on the morning of Tuesday 19 March 1996. He explained that SEAC would be giving further consideration of the measures that should be taken at a meeting scheduled for the following weekend. This was not soon enough for the Government, who were anxious to make a statement about the probable link between BSE and CJD, coupled with the Government's response, before the news leaked out.

4.631 A further meeting of SEAC was convened on the afternoon of 19 March, and continued the following morning, in response to a request to deliver their advice by 10.30 a.m. ⁴⁷

4.632 At the 28th SEAC meeting on 20 March 1996, the Committee agreed a statement for discussion by the Cabinet in preparation for Ministerial statements:

The Spongiform Encephalopathy Advisory Committee have considered 10 cases of CJD which have occurred in people aged under 42 which have recently been identified by the CJD Surveillance Unit, Edinburgh. The Committee have concluded that the Unit has identified a previously unrecognised and consistent disease pattern. A review of patients' medical histories, genetic analysis to date and consideration of other possible causes, such as increased ascertainment, have failed to explain these cases adequately. Although there is no direct evidence of a link, on current data and in the absence of any credible alternative the most likely explanation at present is that these cases are linked to exposure to BSE before the introduction of the SBO ban in 1989. This is cause for great concern . . .

The Committee emphasised it is imperative that current measures to protect the public health are properly enforced and recommend constant supervision to ensure the complete removal of spinal cord.

The Committee also recommend:

1. that carcasses from cattle aged over 30 months must be deboned in licensed plants supervised by the Meat Hygiene Service and the trimmings must be classified as SBOs.
2. a prohibition on the use of mammalian meat and bone meal in feed for all farm animals.
3. that HSE and ACDP, in consultation with SEAC should urgently review their advice in the light of these findings.
4. that the Committee urgently consider what further research is necessary.

The Committee does not consider that these findings lead it to revise its advice on the safety of milk.

If the recommendations set out above are carried out, the Committee concluded that the risk from eating beef is now likely to be extremely small. ⁴⁸

Discussion

4.633 There was much that was unsatisfactory about this series of events. A policy decision was needed. The range of options included:

1. do nothing;
2. debone meat from animals over 30 months;
3. prohibit consumption of animals aged more than 30 months; or
4. slaughter the entire herd.

4.634 SEAC was in a position to advise on its perception of the risk of further transmission to humans and the effect on that risk of each of the options. The choice of options should also have been influenced by:

1. the practicalities;
2. the financial consequences;
3. the need to maintain or restore public confidence in beef; and
4. the implications of international trade.

4.635 It was desirable that there should be a dialogue between Government and SEAC, resulting in Government weighing all the considerations and taking the policy decision. In the event, the policy decision was effectively delegated to SEAC, although SEAC was not well placed to weigh either the practicalities or the political considerations.

4.636 The option selected by SEAC and adopted by the Government proved not to be viable as a result of problems both of practicality and market perception. This outcome was, we believe, attributable to:

1. a tradition of relying upon SEAC to decide policy; and
2. a failure to establish a dialogue between Government and SEAC to discuss possible responses should the link between BSE and the new cases of CJD become established. The need for this should have been appreciated after SEAC's meeting on 1 February, if not before. ⁴⁹