The English Disease

Hugh Pennington

  • The BSE Inquiry by Lord Phillips et al
    Stationery Office, 5112 pp, £324.50, October 2000, ISBN 0 10 556986 0

The remarkable thing about the Phillips Inquiry into BSE is not its cost, £27 million, or its 16 volumes, weighing in at 25 kg, or its overrun – it went on for more than double the year originally planned – but its thoroughness. Digesting the massive final report will be more than enough for most. But there is a lot more: witness statements and transcripts of oral evidence have also been put into the public domain via www.bseinquiry.gov.uk. The Inquiry joins a long English tradition of detailed government-commissioned reports compiled with state-of-the-art technology. The Domesday Book was the first and BSE might be thought of as a tardy riposte to that Norman intrusion – the disease, after all, has crossed the Channel in the opposite direction. In any event, it is clear that the story Phillips tells is peculiarly English, to the point that some Scottish scientists, Welsh public health doctors and Northern Ireland veterinarians were left on the periphery despite their extraordinary expertise, working as they did in government departments known as ‘Territorials’.

There is no doubt at all that BSE is an English disease: it started in England and has claimed most of its cattle victims there. But it is not a parochial matter: its scientific, medical and political repercussions are global and general. As a case study of how science works, how scientists and politicians interact, and how governments cope with uncertainty and changing public attitudes to risk it is extremely important. And of course it is a story as rich in images, subsidiary plots and tragic outcomes as any novel. Recall the TV pictures of the doomed publicity stunt undertaken by the former Minister of Agriculture, John Gummer, showing his attempt to force his daughter Cordelia to eat an over-hot burger and her wise, peremptory rejection of it. Reflect on the work of the American scientist Carleton Gajdusek, who showed the relationship between cannibalism in Papua New Guinea and CJD, won the Nobel Prize for doing so and then went into exile as a convicted paedophile. Inevitably, and rightly, dominating the whole thing are the accounts of the victims of variant CJD, those infected with the BSE agent. Phillips took evidence right at the beginning of his Inquiry about the case of Clare Tomkins, who fell ill with vCJD in October 1996. Because of her love of animals she had been a vegetarian since 1985, when she was 13. Diagnoses of depression, anorexia and agoraphobia were entertained during the early part of her illness. She was given electroconvulsive therapy and sectioned under the Mental Health Act. Her father said: ‘the most harrowing thing was sometimes in bed at night . . . she howled like a sick injured animal. She looked at you as though you were the devil incarnate. She started to hallucinate.’ In March 1998, when he gave evidence, she was still alive but was bed-ridden, doubly incontinent, blind and, as far as anyone could tell, completely unaware of her surroundings. (She died a month later.)

BSE and vCJD belong to the family of diseases called Transmissible Spongiform Encephalopathies (TSEs). Transmissible because they can be passed from individual to individual (although not easily and only by certain routes), spongiform because the brain becomes dotted with microscopic holes, and encephalopathy because the symptoms are caused by brain and nervous system damage. Until BSE, only one TSE – scrapie – was common. For most of its 250-year history this sheep disease has been regarded as nothing more than a bloody nuisance. Infected animals rub themselves incessantly against fence posts and walls because of intense itching, and after a while, they die. But work over the last fifty years has shown that scrapie is very different from any other infectious disease of sheep, and in the whole of pathological science has parallels only in some vanishingly rare brain diseases of humans – notably Creutzfeldt-Jakob disease – and a few other animals. These remarkable differences have caused scientists to pay a lot more attention to TSEs than their economic or public health impact would seem to have warranted.

TSEs have very long incubation periods, of years and decades. But the properties of their infectious agents are far more curious. They are resistant to harsh physical and chemical environments that would kill all other lifeforms many times over – extremes of heat and radiation, and soaking for months in aggressively reactive chemicals such as formaldehyde. And all of many attempts to find an infectious particle like a conventional bacterium or virus have failed. So the central question has been: what is the nature of the infectious agent? There is no doubt that it is unconventional. But to what degree?

Scientific opinion about these matters falls into two categories, consensual and contentious. There is general agreement about the central role played by a single molecule, the prion protein. This protein is found in all the warm-blooded animals in which it has been looked for, from chickens to man. Its function is unknown. Genetic engineers have constructed mice that lack it and seem to have quite happy lives. It is located at the surface of many different cell types in the body; like other membrane proteins, it can be dissolved in chemicals that cause the coiled-up protein chain to uncoil and it can be digested by enzymes which specialise in cutting the bonds between the individual amino acid molecules that are linked to form the long protein chain. In TSEs this protein changes dramatically. It cannot be dissolved, it becomes resistant to enzyme digestion, and it changes its shape by coiling up in a different way. It begins to build up inside cells. It is reasonable to suppose that this is why the affected cells die, causing the loss of brain functions and the appearance of holes. Deposits of the altered protein can be found in the brains, tonsils and appendixes of patients with vCJD. A crucial confirmation of its central role in TSEs is that the genetically engineered mice which lack it are completely resistant to infection with agents such as scrapie that kill normal mice.

There is less agreement about what triggers the build-up of the altered prion protein. The majority view, championed by the Californian scientist Stanley Prusiner, is that the altered protein itself is the infectious agent. When it comes into contact with cells in the tissues of an animal or person that has eaten it or been injected with it, an interaction takes place between the normal prion protein on these cells and the infecting abnormal one, causing the former to become abnormal itself. This then reacts with its normal neighbours in the same way, starting a slow cascade that produces the build-up of abnormal molecules. Some doubt whether this is the whole story. They think that other molecules as well as, or even instead of, the abnormal protein start this process. If abnormal prion proteins were not so insoluble and sticky it would be possible to purify them chemically and show definitively what was present in an infectious sample, but this has not been done. The argument goes on.

The gene that codes for the normal prion protein has been sequenced. In the British population, three common variants are found in this sequence, involving the part of the DNA that codes for the 129th amino acid from the left-hand end of the protein chain. The most common variant is MV and the rarest VV. Over 60 per cent of the population has one or the other. So far, all the vCJD cases have had a different type, MM. There is evidence from other kinds of CJD that this variant may predispose people to develop TSEs. It may be, however, that the main effect of MM is only to shorten the incubation period. Estimates of the eventual size of the vCJD epidemic have to take this into account – are we all susceptible or will the disease target the 40 per cent of the population with MM? Nobody knows.

TSE research has attracted certain kinds of scientist: those who work on problems because they are difficult, and those who seek the big prizes. Of all the dramatis personae in the Phillips Inquiry, Alan Dickinson fits most convincingly into the first group. An intellectually rigorous man who puts science a long way ahead of office politics, he resembles the image that the public has of the brilliant, unworldly scientist. Only someone on another plane would work on the genetics of scrapie. But his virtuoso studies laid the basis for all current work on TSEs. He is a typical product of the British biometrical/statistical school of genetics that was particularly active in the first half of the 20th century. Unlike the ‘Phage Church’ established by the German emigré Max Delbrück in the US in the 1940s – which aimed to do genetics with very rapidly growing bacterial viruses (bacteriophages or ‘phages’) in order to determine the nature of the gene – the biometrical/statistical school focused on how genes behaved and what influences they exerted, rather than whether they were proteins, or nucleic acids, or neither. It treated genes as abstract concepts and left biochemists to worry about what they were made of. Dickinson worked on the factors that determined susceptibility to TSEs, using scrapie as his agent and sheep and mice as the host. By crossing different strains of mice and studying different strains of scrapie he established that a single gene, sinc, controlled the incubation period of the disease.

This work was a tour de force not only because of its conceptual complexity and difficulty, but because each experiment took a year or more to carry out. Sometimes the mice died of old age before the experiments were finished. The contrast with phage work could not have been greater – Delbrück could do a cross in his bacterial system, get all the results, and design his next experiment in less than 24 hours. Stanley Prusiner was indebted to Dickinson and won the Nobel Prize for the straightforward task of putting biochemical flesh on the genetic – more abstract – bones that Dickinson provided. Other members of Dickinson’s team in Edinburgh, Moira Bruce and Hugh Fraser, have developed the best typing tests and produced the most convincing results linking BSE and vCJD. How have these successes been rewarded?

One is forced to conclude that the malignant effect of scrapie in Britain is not confined to its boring of holes in the brains of sheep. Dickinson might have shared a Nobel Prize with Prusiner in 1997, but by then he had taken early retirement from the directorship of the research unit he used to run, a casualty of one of the many ‘rationalisations’ of government-funded science institutes that took place on a grand scale during the Thatcher years, along with massive funding cuts. It is by chance, not design, that the unit still survives. Phillips recounts the whole sorry tale. No doubt those who planned these changes thought that by concentrating scientists in ‘centres of excellence’, better science would result for less money. They defend their actions by saying that they had no choice. They are right in so far as the driving force was the Treasury. Its dark presence lurks throughout the whole BSE saga as insidiously as the agent of the disease itself.

Unfortunately the Dickinson tragedy does not end there. It might be thought that someone with his knowledge of TSEs would have been consulted on the scientific aspects of BSE when it emerged, particularly since experts in the field were extremely rare. But when the Government set up the Southwood Working Party in early 1988 ‘to advise on the implications of Bovine Spongiform Encephalopathy and matters relating thereto’ a deliberate decision was taken to exclude anyone who had worked on TSEs from its membership. In his statement to the Inquiry, Sir Richard Southwood, professor of zoology at Oxford, said: ‘we agreed that we should avoid those who were involved in the controversy surrounding the nature of the agent.’

Phillips disagrees with this approach, arguing that the composition of a scientific advisory committee ‘should include experts in the areas of the advice that is likely to be required’. There can be little doubt that Dickinson’s stubborn resistance to being messed about by bureaucrats had won him a reputation as an awkward chap – for this very reason alone he would have had a beneficial effect on the committee. That he was excluded was not only bad science (science draws its strength not from making hypotheses but from testing them), bad administration and bad politics, but it was bad for public health. It almost certainly meant that people went on being exposed to the BSE agent for longer than necessary.

The other factor – once again – was scrapie. Not long after BSE was discovered, outstanding epidemiological work identified the central role played in its spread by meat and bonemeal fed to cattle. The very reasonable hypothesis was proposed that the first cases were caused by cows eating ground-up sheep infected with scrapie. So, in essence, BSE was scrapie in cattle. What a comfort this was! People had been eating infected sheep for at least two hundred years. Detailed studies had shown not a scintilla of evidence for a connection between scrapie and classical CJD. So it was possible to tell the public that the risk of transmission of BSE to humans ‘appeared remote’. These words were used in the Southwood Report in 1989. To be fair, there were caveats: ‘Our deliberations have been limited by the paucity of the available evidence. Further research in this area is essential’ and ‘if our assessment of these likelihoods is incorrect, the implications would be extremely serious.’ But, as Phillips says: ‘unfortunately this warning and the tentative nature of the Working Party’s conclusions were not appreciated or were lost sight of. Right up to 1996 the Southwood Report was cited as if it demonstrated as a matter of scientific certainty, rather than provisional opinion, that any risk to humans from BSE was remote.’ But one of the most important experiments to test the scrapie hypothesis – feeding cows with material from scrapie-infected sheep – didn’t begin until 1997. Phillips summarises the harm done by the scrapie hypothesis succinctly. ‘From the moment in December 1986 when Mr Bradley’ – the head pathologist at the Government’s Veterinary Laboratory – ‘classified his first minute about BSE as “Confidential”, to the Chief Medical Officer’s reassuring recorded message of 20 March 1996, ending with the statement, “I myself will continue to eat beef as part of a varied and balanced diet,” officials and ministers followed an approach whose object was sedation.’ Meanwhile, despite the rapid disappearance of BSE from British cattle, the malignant influence of scrapie persists. There is serious concern that BSE has infected sheep, but has been overlooked because it is masquerading as scrapie. Tests are underway to look for this. They are very slow and very expensive. All the more reason to regret that their execution was put off for years by the sedative approach.

Secrecy and censorship have always been favourite tools of governments. Phillips had no difficulty in finding examples of their application during the sedative period of the BSE crisis. A good example is the official response early in the affair, in 1987, to the attempt by a member of the State Veterinary Service to publish his findings on BSE. The Assistant Chief Veterinary Officer, his superior, wrote to him:

I am now confirming that the letter to the Veterinary Record which I cleared earlier in the week should not be published. I explained to you that this condition had been discussed by the CVO and the Director of CVL [the Central Veterinary Laboratory], and because of possible effects on exports and the political implications it has been decided that, at this stage, no account should be published.

There was a similar line regarding the informal transmission of information outside official circles: ‘It is essential that VIS [Veterinary Investigation Service] staff must not, at this stage, discuss it with or consult workers at research institutes and university departments.’

We should not be surprised to find secrecy in the civil service, but there is something especially bad about secrecy and censorship in science. They are completely at odds with its norms: universalism, organised scepticism, communality, humility and disinterestedness. It has long been fashionable for sociologists of science to scoff at these values, but the public might reasonably expect scientists charged with looking after their interests to do their best to follow them. How else can trust be established? In the end, of course, it was not only trust in scientists that was destroyed. Phillips sums up: ‘When on 20 March 1996 it was announced that cases of new variant CJD were probably attributable to contact with BSE before precautionary regulations were introduced, the reaction of the public was that they had been misled, and deliberately misled, by the Government.’ Of the mistakes he attributes to named individuals, nearly two thirds were made by civil servants or government advisers with professional or scientific backgrounds – 18 by medical doctors, 15 by vets and five by scientists – as against 17 by other civil servants and four by Government ministers. He apportions particular blame to individuals who should have known better. The English and Scottish CMOs are taken to task for participating in the ‘British beef is safe’ campaign without adding that this was the case only if all controls were working as intended. There were also avoidable communication problems between agriculture and human health departments: for example, the Scottish civil servant who received the reports from the main scientific advisory committee in London regarded them as ‘all Greek’. They were filed away and never reached the CMO. Deirdre Hine, the Welsh CMO, was the exception, in part because some of her colleagues took a particular interest in TSEs.

Some doctors and vets have emerged with credit. The Northern Ireland Chief Veterinary Research Officer had serious doubts that BSE was scrapie in cattle and raised these at the European Commission’s scientific meetings in the late 1980s and early 1990s. The medical microbiologists Richard Lacey and Stephen Dealler of the Department of Clinical Microbiology at Leeds University vigorously challenged the scrapie hypothesis as well as many other aspects of the sedation policy. Their approach was summarised by Dealler: ‘I said to Lacey at the time, “You are being more aggressive than will be effective.” He said a number of times that to try to get things done through official channels would be ineffective. The only way to get things done would be through the media. I found he was right in the end.’ Lacey had been a vocal critic of the Government’s stance on various food safety issues for a long time. He became interested in BSE in 1989, and took a high media profile after a TSE – later shown to be BSE – had been diagnosed in a domestic cat in 1990. In essence what drove them to attack the sedative approach was not a concern that BSE and scrapie were unrelated, but that BSE, whatever its origin, was clearly different from scrapie, in that it had now moved to a new host. They felt that this should ring loud alarm bells warning that there was a possibility of transmission to humans – if the disease had crossed one species barrier in an efficient way, why could it not move across another as easily? They were also concerned that the disease might spread from animal to animal by an environmental route. Scrapie appeared to do this.

Phillips devotes 36 pages to Lacey and Dealler’s activities under the rubric ‘Challenges to the Government’s Approach’. Among other things he describes Lacey’s rubbishing by the House of Commons Agriculture Select Committee in 1990, and a failed attempt at a meeting of minds between officials, scientists and advisers on the one hand and Lacey and Dealler on the other at the MAFF pavilion at the Stoneleigh National Agricultural Showground. He comments:

Professor Lacey and Dr Dealler each gave evidence to us. Each impressed us as a serious scientist motivated by very real concerns about the hazards posed by BSE. Some of the conclusions they reached were speculative, some were extreme and some have been proved wrong. Many have, however, been vindicated as knowledge about BSE has increased. The public concerns raised by media coverage of views expressed by Professor Lacey were unwelcome to MAFF. With hindsight it seems to us that they were beneficial.

Welsh doctors, too, tried to raise their concerns, not with MAFF, but with the Department of Health. Since her appointment as Welsh CMO in 1990, Deirdre Hine and her colleagues, particularly the public health doctors Stephen Palmer and Roland Salmon, had been unhappy about the categorical statements from the Department that beef was safe, and they said as much. They were told to mind their own business by a DH medical officer:

I have done my best, as you acknowledge in your letter, to keep you informed of the main developments but it is quite inappropriate for me to share with you all the detail. If there is an aspect you think the experts may have overlooked, please feel free to raise it with me on the phone or in writing. For my own part, I do not see there is a particular Welsh ‘angle’ to BSE/CJD, and am surprised you feel it necessary to put so much effort into challenging the views of colleagues at DH who are more senior, more experienced in the area, devoted a higher proportion of their time to the topic, and have frequent access to the real experts in the field.

This is the civil service operating in Rolls-Royce mode – no indecision or mincing of words. Defending its patch is what a government department does best.

Phillips had no difficulty in finding examples of a rather muddier approach. The bovine eyeball dissection affair will surely become a classic. The possibility that dissecting cows’ eyeballs in schools might not be a good idea was first raised seriously in November 1989, when ‘specified bovine offals’ were banned from entering the food chain. The following February the Scottish Education Department advised that children shouldn’t dissect them. But in England a more leisurely approach was adopted. Logic chopping prevented a rapid decision. Eyes are extensions of the brain – which was banned. But eyes weren’t eaten by anybody, so were not banned. It was then argued that it would be inconsistent to stop their dissection, because it was still legal to eat them. There was a lengthy debate in the Department of Education and Science. It led to first (August 1990), second (January 1991) and third (February 1992) drafts of advice. Cross-departmental views were then sought. When pressure from the Welsh and from the Department of Health was applied, guidance was finally issued in December 1992, more than three years after the alarm was raised. Phillips sees sedation at work here, too. But he also identifies another important contributory factor: ‘as with all civil service documents, there was an urge to refine and polish wording. As time went on, the delay itself made the issue of guidance less appealing.’ Clearly the Rolls-Royce in production here belonged to the Silver Cloud stable.

Phillips’s conclusion is that in the face of great scientific uncertainty the right things were done – for example, stopping the transmission of BSE to cattle by banning the use of meat and bonemeal in cattle feed, destroying animals with BSE to stop them entering the human food chain, preventing offals likely to contain the BSE agent (such as the brain and spinal cord) getting into the food chain, stopping mechanically recovered meat being extracted from spinal columns, preventing the use of British bovine materials in medicines and cosmetics – but later and not as thoroughly as they should have been. There was a system failure. The deficiencies have been there a long time. Nothing much has changed since Don Price looked at the British civil service from a US standpoint in Government and Science (1954):

The British administrative class is a great deal more efficient than its chaotic counterpart in the United States. But I do not think that our main possibility of improvement lies in an effort to imitate it. Any such closed service is a profoundly conservative force . . . in the sense of looking on the Government and its programme as a single coherent machine in which inconsistencies cannot be permitted. Any novel idea is an inconsistency that could cause temporary waste and disorder and inefficiency and would probably detract from the current programme.

The Phillips Inquiry may drive reform, but he minces his words. The concept of corporate liability for disasters like rail crashes and ro-ro ferry sinkings has not been readily accepted in the English courts. Phillips seems to share this reluctance: although his attribution of blame is tightly focused on the actions of individuals, the civil servants responsible for policy at the highest level – permanent secretaries and their close colleagues – escape lightly from his strictures. More than any other group, they had the power to challenge the strategy of sedation. They did not. But although Phillips is lenient, the evidence given to his Inquiry and the description of events in his report are a harsh indictment of the civil service. Gifted amateurs with non-science first-class Oxbridge degrees may be able to write brilliant position papers proving that black is white, but they should not be occupying the heart of government. Scientific literacy was in such short supply at top levels during the BSE crisis that at crucial moments policy-making was handed over to scientists. This abdication of responsibility by the executive should never happen again. The Government’s need for scientific advice is bound to increase, but those who hold senior positions in the executive must understand how to use it properly. If polymaths get onto the Whitehall fast track this Inquiry may have been worth it.