Volume 6: Human Health, 1989-96
5. Human health developments: 1 January 1991 to 31 March 1995
Developments in knowledge and understanding about BSE from 1991 to 31 March 1995
Introduction
Transmission of BSE to primates
Increase in the host range for BSE
Developments in understanding about dose
Report on TSEs by SEAC in September 1994: Transmissible Spongiform Encephalopathies: A Summary of Present Knowledge and Research
Discussion

Introduction

5.235 During the period 1991 to 31 March 1995 there were several significant milestones in the development of knowledge and understanding about BSE. We have just described the discovery of BSE in the distal ileum of calves in mid-1994. Other developments and the responses of MAFF and DH at that time are described in this section. Public pronouncements relating to these developments are covered in a separate section (see paragraphs 5.295-5.394). Further details of the science behind these developments are given in vol. 2: Science.

5.236 Developments in relation to the incidence of CJD in farmers and teenagers during this period are described in vol. 8: Variant CJD.

Transmission of BSE to primates

5.237 On 14 February 1992, the Medical Research Council (MRC) advised MAFF and DH that BSE had been experimentally transmitted by inoculation to marmosets, a primate species. ¹

5.238 Mr Lowson (Head of Animal Health (Disease Control) Division, MAFF) advised Mr Gummer of the results and noted:

At first sight this is not particularly surprising and has no implication for human or animal health. Nevertheless we have agreed with DH that it would make sense to call together members of the Tyrrell Committee as quickly as possible to consider the matter, and in the light of their advice we can consider with DH how to put the information into the public domain. ²

5.239 On the same day, Mr Thomas Murray (Head, Environmental Health and Food Safety Division, DH) minuted Dr Kenneth Calman informing him of the results. Mr Murray said that 'news of this development has not yet been made public but there is always a risk that details will leak out and attract media attention before a formal DH/MAFF co-ordinated announcement'. He attached a background note by Dr Ailsa Wight, who was responsible for handling BSE matters, ³ which included the following points:

Significance of New Findings

Transmission of other SE agents to primates, including marmosets, has occurred in the past, and is well recorded. CJD, kuru and scrapie agent have been successfully transmitted to primates.

. . .

The finding is not therefore particularly unexpected, although interesting. Moreover, it does not have any particular implications for human health with respect to BSE agent.

Action

As a primate is affected, in view of any potential for the development of human disease, DH is taking this finding seriously. We are consulting with independent expert members of the Tyrrell Committee, which advises the Government on all matters relating to SEs.

. . . It is vital we at DH co-ordinate our response with MAFF, though perhaps in this instance our interest might be greater than MAFF's as primates are one step removed from humans.

LINE TO TAKE

DH and MAFF [are] closely monitoring research developments in the BSE field on a broad front and are aware of the recent (Marmoset) results.

At this stage there would seem to be no significant implications for present BSE control measures. However, the Tyrrell Committee has been asked to give special consideration to the study results. ⁴

5.240 Dr (later Sir) Dai Rees, Secretary then Chief Executive of the MRC (1987-96), wrote to Dr Calman on 21 February, and said in relation to the experiment:

We were informed about this on 14th February, when we understood that MAFF would shortly be issuing a press statement. At the beginning of this week it became clear that neither DH nor MAFF would be prepared to go public until the Tyrrell Committee (or rather key members of that Committee) had met to consider the matter. This could not be arranged until the afternoon of 27th February. It seems to us, however, that the outcome of the experiment was so predictable, that any press statement would give it undue prominence, and indeed could lead to unwarranted public anxiety. I am doubly apprehensive that it is proposed that the release be so delayed to allow time for a possible leak; if there is indeed such a leak, to follow it by a press release would be a real shot in the foot.

I would therefore urge that any thought of a press statement be abandoned. ⁵

5.241 The members of SEAC considered the transmission of BSE to marmosets, at the request of DH, at an informal meeting on 27 February 1992.

5.242 It was noted in the minutes of the meeting:

. . . that although pathological study of the marmosets was continuing, enough had been done to confirm the presence of an SE. In the scrapie cases, there were no gross pathological findings. Histopathology revealed moderate changes in the brain stem and severe vacuolation in the cortical areas, which was asymmetric in the cerebral hemispheres. In the BSE cases, again there were no gross changes. Histopathology was similar to the scrapie cases but almost all confined to the brain stem, basal ganglia, and thalamus, with much less vacuolation in the cerebral cortex. ⁶

5.243 The members of SEAC concluded that the inoculation into the brains of the marmosets was 'more likely' to have caused BSE than 'giving it by mouth', on the basis of previous studies of spongiform encephalopathies. Although marmosets had not previously been infected with BSE, 'they had been infected with S.E including scrapie using similar methods so the results of this experiment are not surprising'. SEAC concluded 'that the measures at present in place provide adequate safeguards for human and animal health'. ⁷

5.244 Dr Harry Baker of the MRC ⁸, who had conducted the experiment, told the Inquiry in oral evidence that, at the time, he thought that Dr Rosalind Ridley ⁹, his MRC co-worker on the experiment, and he were in agreement with SEAC's conclusion. ¹⁰

5.245 MAFF and DH then published a news release on 4 March 1992, giving details of the experiment and SEAC's conclusion, which concluded:

Although it was already known that marmosets were susceptible under similar artificial laboratory conditions, to other spongiform encephalopathies, the Spongiform Encephalopathy Advisory Committee, chaired by Dr David Tyrrell, were immediately asked to advise on the implications of this experiment. The Committee concluded that the results of the experiment were not surprising and had no implications for the safeguards already in place for human and animal health. ¹¹

The press release is detailed in full in paragraphs 5.298-5.299 below.

5.246 In June 1992, SEAC published an Interim Report on Research and considered the work to date on BSE and transmissibility. It noted:

The epidemic of the bovine disease sparked off renewed interest in transmissible SEs generally and several species are now known to have been affected by this group of disorders . . . and others have been shown to be susceptible to experimental challenge. The most common of these diseases is scrapie in sheep, the others (excepting BSE) being reported infrequently. There remains no evidence to suggest that the human disorders are causally associated with those in animals. ¹²

5.247 The interim report then repeated the conclusion SEAC had reached on 27 February 1992 in relation to the marmoset experiment:

At present, the Committee are satisfied that all the necessary safeguards are in place to minimise further spread of spongiform encephalopathies in animals and to prevent any risk of transmission to humans. ¹³

5.248 In oral evidence, Mr Gummer referred to the marmoset experiment when asked whether he had considered, at any stage, that possibly 'Southwood is wrong and there is a link between BSE and some disease of humans'. He stated:

. . . We were always asking questions. If I may say so they were of a more precise kind than that. We would say: 'Well, what happens if this happens? What happens if that happens?' Constantly doing that. And I think that was the proper way to do it. We were faced with the very clear and almost - I only say almost because I would not say like to say any more - almost universal advice which was very clearly said. There was Southwood itself, then there was the international statement which quite clearly said this, then Dr Tyrrell said it, that the risk was so remote as for all practical purposes to be ignored, and we went back to them all the time. But what we went back to was to say this piece of information that we have just got, this marmoset, this issue, does that make any difference to your advice?

Now that seems to me the proper way to approach it. In other words, we had asked the scientists to give us the best advice in the circumstances in which they were. Our point of view, having accepted that advice, was constantly to make sure that those circumstances had not changed, and that their advice was no different. And during the period of time in which I was Minister and my junior Ministers were with me, that science was tested all the time, but it did not change. The advice was and continued to be that the risk to human beings was remote . . . ¹⁴

5.249 Sir Kenneth Calman, in reference to the marmoset experiment, said in his statement to the Inquiry that 'these experiments were significant in the fact that they extended the host range of experimental BSE to include a primate species'. ¹⁵ He then said in oral evidence that the result of the marmoset research was:

Another bit of evidence, albeit experimental, which simply confirmed the fact that transmission was possible. But it also provides me with an opportunity of saying how that would be dealt with. And that would be that we would have asked, as we did, SEAC and any other expert committee to give us that advice. We relied very heavily on independent experts' advice to look at the data, give us their views from which we could help Ministers take things forward. They did look at that and concluded that no further action was required at the time. ¹⁶

Increase in the host range for BSE ¹⁷

5.250 Between 1991 and March 1995, a number of zoo animals succumbed to spongiform encephalopathies. A puma in Chester was reported in 1991 to have feline SE (FSE), possibly from ingesting infected cattle tissue. ¹⁸ In 1992 a cheetah in Australia, exported from Marwell Zoo in England, died of FSE. It was noted in the minutes of a meeting of the Central Veterinary Laboratory (CVL) and the Neuropathogenesis Unit (NPU) on 8 April 1992 that the cheetah (while in England) 'had been fed on knacker meat (containing little offal, but possibly spinal cord) at a zoo in an area of relatively high BSE incidence'. ¹⁹

5.251 SEAC referred to the CVL/NPU meeting minutes at their meeting on 28 April 1992, and recorded that the captive wild cat cases 'further weakened the Southwood Working Party's view of the likely limited host range of SEs'. ²⁰

5.252 The cases were discussed in an article in the Independent on 29 June 1992 (discussed in paragraphs 5.305-5.306 of this chapter).

5.253 Dr Tyrrell was asked in oral evidence if the transmission of BSE to cats and captive wild cats altered his perception of the risk to humans:

LORD PHILLIPS: Were these matters which shifted your perception as to just how unlikely it was that BSE would be transmissible to humans?

DR TYRRELL: It is very difficult, even with hindsight, sir, to recall. I think it shifted it a bit. I think there are two points: one is that in fact what you have just described so clearly took place over quite a long period of time, because first of all the epidemic took about a year to build up, secondly the study of the cat agent had to show it to be a really transmissible spongiform encephalopathy, and then finally it had to be characterised, which takes a year or more, to show that it really was indistinguishable from the BSE agent. By that time years had gone by. I think my main comment would be that I had always been worried whether BSE would pass to man, and I saw this as a possible example of what might happen if it did get to man. We came to the conclusion that it was likely to have been animals which had been fed pet food, offal off the market stall or something like that, and this was the consequence. So it just meant that we had to be very serious about considering whether there was evidence of it spreading to other species.

Incidentally, if I may just add one or two other things, there were a number of other species besides even large cats: the kudu, the nyala, so we knew it did not have to go only to cattle already. ²¹

5.254 In September 1992, three kudu ²² from London Zoo succumbed to SEs. There had been previous reports of SEs in antelopes - a nyala had succumbed to an SE in June 1986, a gemsbok in June 1987, an Arabian oryx in March 1989 and a greater kudu in August 1989. ²³

5.255 Mr Lowson minuted Mr Soames on 25 September 1992 to inform him of the infection in the three kudu. Mr Lowson advised that in one animal transmission from dam to calf appeared to be 'the most likely source of infection'. He noted that the case was likely to be published in the Veterinary Record and the zoo 'had not made a secret' of the case. He had prepared a background note and answers to possible questions.

5.256 The background note said:

. . . In one animal born after contaminated feeds were withdrawn, the source of infection may have been its mother as she died of the disease four months after calving. The most recent case was born in August 1990, long after the withdrawal of potentially contaminated feed, and his mother appears still to be healthy. It therefore seems that the disease may have been spread from animal to animal or indirectly via the environment. This adds to the evidence that these animals are particularly susceptible to the disease (suggested by the possibility of maternal transmission and the short incubation period observed in the past). Why they should be so susceptible, and why they apparently transmit infection (as sheep do with scrapie) while cattle apparently do not transmit BSE, is unknown.

5.257 A possible question, 'Is there any risk of spread to humans?', was answered:

There is no evidence of any risk to human health. Similar diseases, e.g. scrapie in sheep and chronic wasting disease in mule deer and elk, also spread from animal to animal. There is no evidence of any connection between an animal SE and any human spongiform encephalopathy. As a measure of extreme caution, to deal with the remote risk that the BSE agent might be different from those of such long-standing diseases, those cattle tissues which might be harbouring the BSE agent in animals which have not shown clinical signs are banned from human and animal consumption. And suspect BSE cases are slaughtered and completely destroyed. ²⁴

5.258 Mr Soames referred to the minute in his statement to the Inquiry:

I am sure that I would have sought advice from officials on whether these findings had any relevance to human health, and was told that they did not, and that there was no need to review the public message about human health (although I have no record of this). ²⁵

5.259 At their meeting on 15 October 1992, SEAC considered a paper prepared by MAFF on the incidence of SEs in cats and exotic species. ²⁶ SEAC concluded that the apparent high susceptibility of kudu was not relevant to BSE in cattle. No discussion on the implications for human health was recorded at this meeting. ²⁷

5.260 In October 1992, London Zoo introduced safety measures to prevent any risk to the public and zoo staff from the remaining infected kudu. Tools used in the kudu pen were not to be used elsewhere, boots and overalls were to be changed on entering and leaving the pen, the kudu were not to be moved from the pen, and all waste from the kudu pen was to be incinerated. The kudu were not considered to be a risk to the public. ²⁸

5.261 Professor John Collinge, Professor of Molecular Neurogenetics at St Mary's Hospital and a member of SEAC since December 1995, was asked in oral evidence:

Had your perception of the likelihood or unlikelihood of transmissibility to humans been changing over the years up to 1995?

5.262 He replied:

Yes, it had. Certainly the appearance in domestic and captive wild cats was a very important development. It demonstrated that you could no longer really plausibly argue that BSE was just scrapie in cows with all the same properties. This agent, wherever it had originated from, had quite different biological properties to scrapie as manifested by the extended host range affecting species, including things like nyala and kudu as well as the cats that had not been affected by scrapie before, so far as we were aware.

Whether humans were part of that extended host range of BSE was an entirely open question. The fact that it appeared in cats did not mean that humans were any more at risk. It may be that we were less at risk than cats or more at risk than cats, but it certainly put to bed the idea that this was just going to behave like sheep scrapie. ²⁹

Developments in understanding about dose

5.263 In vol. 2: Science we examined how understanding about dose (and in particular, the amount of infectious material sufficient to cause infection) developed during the BSE story. We also discuss dose in relation to animal health issues in vol. 5: Animal Health, 1989-96. In the following paragraphs we shall look briefly at the results of two experiments that demonstrated oral transmission of BSE using only small amounts of BSE-infected material, in the first case to sheep and in the second case to cattle. Before these results were known, many MAFF scientists and officials assumed that the amount of infectious material sufficient to cause infection would be much higher. The results might therefore have provided an opportunity to review the BSE control measures that had so far been introduced.

5.264 The results from both experiments were widely known within MAFF by the end of 1994, but, as described below, we have seen some evidence to suggest that preliminary results for the sheep experiment were sent to some MAFF officials in 1990. We have tried to determine when MAFF first knew about these results, but without much success.

Oral transmission of BSE to sheep

5.265 The NPU, part of the Institute of Animal Health (IAH), initiated an experiment in mid-1988 with groups of sheep and goats, which were given either 0.5 grams of BSE-infected cattle brain homogenate orally or 0.05 grams by intracerebral inoculation. The sheep used in the experiment were from two lines selected and bred for their different responses to scrapie infection: the 'positive' line sheep were susceptible to scrapie challenge and the 'negative' line sheep were not. At the time, it was known that natural scrapie in goats was very rare. The sheep and goats were monitored to determine whether they succumbed to the disease. The two routes of infection were shown to be almost equally efficient in transmitting the disease, and the results highlighted the ability of the BSE agent to infect orally with a small amount, even allowing for a species barrier (ie, cattle to sheep). ³⁰

5.266 Senior officials at MAFF were aware of the results of this work by late 1994. On 2 December 1994, in a minute to the Minister and copied to others in MAFF, Mr Packer (Permanent Secretary) stated that 'one experiment has shown that 0.5gm of infected raw cow's brain fed to sheep will cause BSE'. ³¹

5.267 Dr Chris Bostock (Head of Division of Molecular Biology, IAH, 1989-97) told us that the results would have been known to some MAFF officials in 1990:

Those responsible for this experiment were aware early in 1990 that one of the six orally dosed "positive" line sheep was showing clinical signs of a transmissible spongiform encephalopathy. Post mortem histopathological examination of the brain subsequently confirmed that this animal had a transmissible spongiform encephalopathy. This fact was recorded on the April 1990 summary data sheet for the transmission experiments that would have been sent to MAFF to keep them up to date with progress. The first appearance of clinical disease in the above 'positive' line sheep was followed some 200 days later by a transmissible spongiform encephalopathy in one of the orally dosed 'negative' line sheep (confirmed November 1990) and, after a further 200 days by a transmissible spongiform encephalopathy in one of the orally dosed goats. Apart from being recorded on the up-dated data sheets which were regularly sent to MAFF, the incubation periods for these latter two apparent transmissions of BSE were noted in a letter from David Taylor, dated 17 January 1992, to Ray Bradley shortly after confirmation of the disease status of the goat. ³²

5.268 Dr Bostock added that interim results from this experiment were published in the Veterinary Record in October 1993, but observed that proof of transmission of BSE to these animals had to await strain typing which was completed in November 1993 and 'MAFF were informed shortly afterwards'. ³³

5.269 In oral evidence to the Inquiry Dr Kenneth MacOwan, Scientific Liaison Officer for MAFF, stated that:

One of the issues where the Chief Scientists Group has been, if you like, pro-active is in trying to stimulate research on BSE in sheep, to the work in 1988, SE 1402 showed that BSE would transmit to sheep. Also that it caused the disease in sheep that were genetically not susceptible to scrapie. These results were available in late 1989, 1990, 1991, 1992. They were all published. It seemed to many of us, not just CSG of course, that this should be taken further. If you like, it is the obverse of what we were talking about earlier of putting scrapie into cows. In spite of that, there was not really much support for doing this.

Now, I think it was discussed in SEAC more than once; and I have often asked myself why it was not taken forward earlier; and you can come back to the fact that we knew little about the genetic susceptibility of sheep to scrapie. We knew nothing about the genetic susceptibility of cows to BSE. And these were critical facts in taking this forward. ³⁴

5.270 In a statement to the Inquiry, Mr Meldrum said:

I note that the 'interim results' of the experiment conducted at NPU which involved oral dosing of sheep and goats with 0.5 grams of BSE infected cattle brain, were not published until October, 1993. Also, even at that stage NPU did not know that they had transmitted BSE orally to sheep. The recording by NPU in November 1990 of the appearance of a scrapie-like disease in the 'negative line' sheep was very much later than the time during which MAFF was considering the proposed SBO ban. ³⁵

. . .

As far as I am aware the preliminary results of NPU's experiment involving the intracerebral inoculation of BSE to sheep and goats were not available until November/December 1989, and the results of oral exposure of sheep and goats to BSE were not available until, at the earliest . . . November 1990. In actual fact the first results did no more than confirm that sheep and goats were susceptible to BSE by exposure by this route and did nothing to inform about the infective dose even if the dose, in the inoculum was known. ³⁶

5.271 There was some further discussion with Mr Meldrum about this experiment during oral evidence, in particular the rationale behind the selection of 0.5 grams of BSE-infected material for oral dosing:

MR WALKER: I wanted to refer you to paragraph 3 [of Dr Bostock's statement S108A]:

'We [that is the Institute of Animal Health] had been supplied by MAFF with samples of brain material from four BSE affected cattle in order to set up a number of mouse transmissions. The material that was left over, about 10 grammes I believe, was pooled, homogenised and apportioned between experimental animals as follows . . .'

Then at the first bullet point there he deals with intracerebral inoculation and there each of the sheep and goats in question received 0.05 of a gramme of this material.

The next bullet point deals with oral dosing. There the sheep and goats were given half a gramme. Dr Bostock continues:

'Thus the size of the oral dose was determined not so much by any theoretical consideration of what might constitute an infectious dose but by the limitations imposed by the experimental design and the material available.'

It seems that when making what use they could of this 10 grammes of material, those involved thought half a gramme of the pooled and homogenised brain was likely to contain a sufficient oral dose of BSE agent to see if sheep and goats would succumb. Do you agree that that is what seems to have been the position?

MR MELDRUM: Quite clearly the experiment had a number of purposes, one of them was that, yes, to determine whether a particular dose would cause disease in sheep. It was not even certain of course that BSE would transmit to sheep at that stage, we did not know. That was the first thing. Secondly, yes, it might give some indication as to dose. Can I put that in context?

MR WALKER: I do not suggest the experiment was designed to find the dose. It was just designed to see whether they would succumb?

MR MELDRUM: Indeed, both by intracerebral inoculation and also by oral dosing. Of course in the timeframe I thought we were considering that information was not available. I put that into my statement, as you know...

MR WALKER: The result was not available.

MR MELDRUM: I am not even sure by the way Mr Walker that I knew of the detail of the planning of that either.

MR WALKER: That is what I wanted to ask you about. Can you recall whether you knew that they were using half a gramme as an oral dose?

MR MELDRUM: Frankly, I cannot recall. ³⁷

The attack rate experiment

5.272 An 'attack rate' experiment started at the CVL in January 1992 involved groups of cattle orally receiving doses of 1 g, 10 g, 100 g or 3 x 100 g of BSE-infected cattle brain homogenate and being monitored to see whether they succumbed to the disease. ³⁸ We describe below consideration of the interim results of this experiment, when it became clear that one gram of BSE-infected cattle brain homogenate could be sufficient to cause disease when transmitted orally.

5.273 On 8 September 1994, MAFF officials, including Mr Kevin Taylor and Mr Andrew Fleetwood of the SVS, and Mr John Wilesmith, Head of Epidemiology, CVL, met the UK Agricultural Supply Trade Association (UKASTA). The experiment was discussed and it was noted:

Although the work was not yet complete, the indications were that a very low dose was sufficient to cause BSE. ³⁹

5.274 Mr Gerald Wells, Head of Neuropathology Department, CVL, was asked in oral evidence whether he was surprised to learn that one gram of BSE-infected material was an effective dose:

MR WELLS: Yes, I think it was rather a surprise to us initially that 1 gramme of brain extract - brain homogenate from affected cattle would affect another animal. It had implications that material that had gone through the rendering process and subsequently ended up in meat and bonemeal had to be in - could be in very small quantities to result in infection.

MR WALKER: Thank you. Are there any other implications of that result that you thought were important?

MR WELLS: I think it was the first time that we realised that any species could be infected by such a small dose relative to their body weight. And so although this was a ruminant, it had implications also for the possibility that in monogastric animals, relatively small doses would be effective by the oral route.

MR WALKER: When you say monogastric animals, what are you referring to?

MR WELLS: I am including all mammals that have one stomach, including man of course. ⁴⁰

5.275 On 28 February 1995, Mr Meldrum informed Mr Packer about the attack rate results and indicated that the amount of unprocessed brain needed to cause BSE was very small. He explained that further studies were necessary to determine the minimum infective dose. He also commented:

The findings may help to explain why the feed ban was less effective than intended, and they will certainly cause UKASTA uneasiness. This supports our view that we should tighten up our controls on the disposal of the specified bovine offals; an issue we have discussed with Ministers. ⁴¹

Studies reported later in 1995 also showed that part of the bovine eyeball contained detectable levels of infectivity. ⁴² This is discussed in Chapter 8.

5.276 Some of the provisions in the Specified Bovine Offal Order 1995, introduced in August 1995 (Chapter 6 of this volume), were a consequence of these findings about infective dose. The Order prohibited the practice of removing the brain from the skull and required the entire skull, including the eyeballs, after removal of the head meat, to be disposed of as SBO.

5.277 The minutes of SEAC's meeting of 5 January 1996 record in relation to the attack rate experiment that definite clinical signs had now been seen in the 1 g challenge group, and that pathology was awaited. ⁴³

Report on TSEs by SEAC in September 1994: Transmissible Spongiform Encephalopathies: A Summary of Present Knowledge and Research

5.278 In September 1994, SEAC produced their report Transmissible Spongiform Encephalopathies: A Summary of Present Knowledge and Research. This was their second report ⁴⁴ and its aim was to summarise what was known about the TSEs, providing information on research both completed and under way. In the preface to the report, SEAC commented: 'We believe the time has come to set out our understanding of these diseases since this forms the scientific basis of the advice we give.' ⁴⁵ The MAFF Minister, Mr Waldegrave, announced publication of the report in an answer to a Parliamentary Question on 7 February 1995.

5.279 The report's coverage of risk assessment, CJD surveillance and monitoring, which was part of chapter 5 on transmission, was as follows:

The SEAC has continuously reviewed the new data emerging from the epidemiological and other studies on the BSE epidemic with a view to making a judgement of the risks to man and other species. The risk to man from BSE depends on the inherent risk that the BSE agent is a human pathogen, which cannot yet be evaluated, and on the level of exposure to the pathogen, which can. Since scrapie was first clearly described in the literature of the 18th century there has been no epidemiological linkage of the disease, or indeed any animal TSE, with human disease, or vice versa. This does not prove there is no risk, but it suggests that any risk is probably small. To check that it is, the only means is to continue the in-progress CJD surveillance programme. This is because any unaccountable rise in incidence of CJD might hypothetically derive from animals. The logical target origin would be BSE, because it is a new disease and had occurred at a high incidence.

Twelve years after the first effective exposure of cows to BSE agent no such cases in man have been identified. Two recent cases of sporadic CJD in British dairy farmers are regarded as chance occurrences, not least because the clinical signs and other features are entirely consistent with a diagnosis of sporadic CJD. They are not like those in kuru or in peripherally exposed iatrogenic cases, which experts consider would be the more likely clinical presentation of BSE-derived infection. Our conclusion therefore is that, as the Southwood Working Party determined, taking all the available evidence together, the risk to man from BSE is remote. Nevertheless, advice given by them and this Committee has been aimed at reducing exposure of humans to the BSE agent. Long term this is achieved by the ruminant protein feed ban which is already showing evidence of success in eliminating BSE in the cattle population and preventing new infections of all ruminants via feed. In the short term the compulsory notification, slaughter and complete destruction of clinically suspect BSE cases, together with the SBO ban (including the extension to include the distal ileum and thymus of calves under 6 months of age used for human consumption) is protecting consumers from any significant exposure.

We are also content that the bioassay of tissues from confirmed, affected BSE cattle realistically reflects the tissues in which the agent may be present in significant quantity (brain and spinal cord) and those in which it is not detected (muscle, milk, liver, kidney, heart, testis, ovary, semen, tonsil, spleen, gut lymphoid tissues and many others). We believe that these measures and others relating to biologicals prepared from bovine tissues, or used in their manufacture (another potential source of BSE infection for man and animals), are sufficient with current knowledge to satisfactorily protect human and animal health.

Although we do not know for certain the sources of FSE in domestic cats, all evidence (temporal and geographic occurrence of the disease, and agent strain typing) points to a feed source and probable origin from BSE rather than from scrapie. The initial cases of SE in all the captive wild ruminant species, except the scimitar-horned oryx, were exposed to the same infected feed as cattle. The origin of infection in the scimitar-horned oryx and subsequent cases in greater kudu and eland is not known. The wild FELIDAE affected by FSE have been exposed to raw, central nervous tissue from potentially BSE-affected/infected cattle carcasses. 'Species jumping' is not an appropriate term to use since all these species have been exposed, probably via feed, provided 'artificially' by man. Indeed without man's interference BSE itself would never have occurred. In conclusion, therefore, our scientific assessment is that the risk to man and other species from BSE is remote because the control measures now in place are adequate to eliminate or reduce any risk to a negligible level. We do however point out that any species exposed already and before any bans were effective could be incubating disease, and therefore continuous monitoring is very important until any possible incubation period has been exceeded. ⁴⁶

5.280 The report was published in February 1995, under cover of a news release which stated that it:

. . . summarises what is now known about TSEs. The Report provides an insight into research both completed and underway. ⁴⁷

5.281 It appears to have attracted no press coverage.

Discussion

5.282 One of the strangest features of the BSE story is the fact that nobody appears to have attached significance to the results of the NPU BSE into sheep experiment. The first point of significance was that BSE transmitted into negative line sheep, which were not susceptible to scrapie. This was one of a number of factors which threw doubt on Mr Wilesmith's theory as to the nature of the agent.

5.283 Much more significant, however, was the fact that 0.5 gram of infective material had proved sufficient to transmit BSE across a species barrier by the oral route.

5.284 When the attack rate experiment demonstrated that 1 gram of infective material was sufficient to transmit BSE orally within the species, there was widespread surprise. The result led to an appreciation of the possible significance of:

1. Contamination of MBM designed for animal feed with SBO in the course of rendering, and
2. Contamination of ruminant feed with monogastric feed containing such MBM in the feed mills.

5.285 Knowledge that 0.5 gram had sufficed for oral infection of a negative line sheep was available as early as November 1990. It is extremely unfortunate that this did not lead to an appreciation of the risks of cross-contamination at this stage.

5.286 It seems to us that had arrangements for coordination of all BSE research been put in place the significance of the NPU experiment would have been likely to be noted by those responsible for the coordination and appreciated by officials in MAFF and DH.

5.287 The joint news release after the Southwood Report had informed the public that the risk of transmission of BSE to humans appeared remote and that it was very unlikely that BSE would have any implications for human health. ⁴⁸ It had reported that the Working Party believed that risks as then perceived would not justify special labelling requirements for products containing either bovine brain or spleen.

5.288 By September 1994 much had occurred to alter the perception of risk. SEAC's report recorded that it was possible that BSE was the source of infection of newly recognised SEs in:

(i) Gemsbok

(ii) Arabian oryx

(iii) Greater kudu

(iv) Eland

(v) Cat

(vi) Moufflon

(vii) Puma

(viii) Cheetah

(ix) Scimitar-horned oryx.

5.289 FSE had been reported in 57 domestic cats by September 1994.

5.290 The report referred to measures that included the human and animal SBO bans with the words:

Control measures are necessary for public health and animal health reasons, the former because the BSE agent may be a human pathogen . . . ⁴⁹

5.291 Some 36 pages later, there followed the passages on risk assessment set out above.

5.292 The careful reader might conclude that SEAC had assessed the risk of transmissibility to humans as significantly greater than had the Southwood Working Party, which had not thought that the risk justified labelling products containing spleen or brain, let alone banning them. SEAC described the risk as remote because of the reduction of that risk attributable to the control measures in place, which included the SBO ban.

5.293 SEAC did not, however, clearly spell out that their perception of risk differed from that of the Southwood Working Party. They stated 'our conclusion therefore is that, as the Southwood Working Party determined, taking all the available evidence together, the risk to man from BSE is remote'. ⁵⁰ This might have deceived the less careful reader into thinking that nothing had changed.

5.294 We do not criticise SEAC for what was a detailed and careful analysis of the existing data. None the less, we think it a pity that their report did not spell out more clearly and simply the fact that perception of risk had changed since Southwood. Had they done so, their report might have attracted some attention and resulted in the public being better informed about risk.