Volume 2: Science
1. Introduction

1.1 Soon after the recognition of a new, fatal disease in UK cattle, it was realised that the disorder was one of a very unusual group of neurodegenerative diseases, ¹ the spongiform encephalopathies, ² which affect both humans and animals - for example, Creutzfeldt-Jakob Disease (CJD) in humans and scrapie in sheep. The new disease was therefore dubbed Bovine Spongiform Encephalopathy (BSE). Spongiform encephalopathies which can be transmitted experimentally are known as transmissible spongiform encephalopathies (TSEs). TSEs are not caused by the micro-organisms usually associated with infectious diseases, but by less conventional agents. This fact led to great difficulties in the diagnosis, control and prevention of BSE. In particular, the disease could not be diagnosed by routine blood and serum tests, because the agent did not appear to evoke the production of antibodies by the host animal. Clinical suspicion of disease could only be confirmed post-mortem, from microscopic examination of the brain.

1.2 In December 1986, when the novel cattle disease was first identified, there was much speculation about the cause of TSEs. These diseases were known to involve the abnormal accumulation in nerve cells of a protein which was normally present, but did not accumulate, in those cells. It was also known that the protein had changed in structure from a soluble to an insoluble form. This meant it was resistant to the normal process of degradation (described in paragraph 1.32 below).

1.3 There were, however, several different views as to how the abnormal protein was generated. Early work in the 1960s suggested that the scrapie agent could replicate without nucleic acid (ie, DNA or RNA). ³ This led Griffith to propose mechanisms for the self-replication of proteins. ⁴ Drawing on his work, Prusiner in 1982 proposed that the infectious agent for TSEs might consist of protein and nothing else. He postulated 'proteinaceous infectious particles', for which he coined the term 'prions'. ⁵ At first considered heretical, by 1986 this hypothesis was gathering ground. Later Prusiner and colleagues would suggest that these prions could underlie inherited, as well as communicable, diseases. They would also conclude that prions multiply in (to use Prusiner's own words) 'an incredible way': they convert normal protein molecules into dangerous ones, simply by inducing the benign molecules to change their shape.

1.4 In 1986 Prusiner's initial hypothesis was not fully substantiated and some scientists continued to maintain that the conveyers of transmissible diseases required genetic material, composed of nucleic acid, in order to establish an infection in a host. They emphasised that viruses, among the simplest microbes, rely on nucleic acid to direct synthesis of the proteins needed for survival and replication. It was suggested that the agent might be one of the smaller viruses which were difficult to isolate. One proposal postulated a new class of agent, 'virinos', which were viral particles encased in immunologically neutral proteins. It is no overstatement to say that controversy raged. Much has since been learned about the molecular biology of prions and their relationship to the pathogenesis of TSEs. We explain later why, despite still being poorly understood, the prion hypothesis forms the basis of the current understanding of TSEs.

1.5 The complexity of the science of TSEs undoubtedly led to uncertainties about the course of the BSE epidemic and the risk it might pose to human health. This volume discusses the investigations that were undertaken and the results obtained.

1.6 Chapter 2 is an account of the scientific knowledge of TSEs that existed in 1986. It was against this background that the scientists who examined the early cases of what was later identified as BSE had to reach a view about whether this was a new disease and, if so, of what kind. Important new findings about TSEs made after 1986 are also referred to, in order to clarify matters misunderstood or poorly understood at the time and, where appropriate, to bring the reader up to date with developments key to our understanding of these diseases. Such material is clearly identified within the account.

1.7 Chapter 3 discusses the evolution of knowledge and understanding of BSE based on the research initiated in response to it. The conclusions drawn from these contemporaneous studies are discussed, in terms of what was known at the time, as well as what is now known from more recent work. The chapter is presented in several sections, describing the initial epidemiological investigations; alternative possible courses that have been suggested for the epidemic; mechanisms by which the epidemic has been maintained; the importance of dose; and the infectivity and transmissibility of the disease. There is also a discussion of the incidence of BSE in Europe, as well as a discussion of the possibility that BSE has been transmitted to sheep.

1.8 Chapter 4 explores the evidence of a link between BSE and the appearance of a new variant of CJD (vCJD) in young people. The work of the CJD Surveillance Unit, and the conclusions of the Spongiform Encephalopathy Advisory Committee (SEAC) on this question up to 20 March 1996 are described in volumes 8 and 11 respectively. However, a substantial amount of data (particularly experimental data) has been obtained since 20 March 1996. We explain why these data dispel some of the doubts that existed at the time about a link. The chapter also contains a discussion on the future incidence of vCJD.

1.9 The development of tests to diagnose TSEs is described in Chapter 5, along with attempts to find effective treatments for the diseases. Once more, this chapter contains material obtained after 20 March 1996, so that efforts to develop tests and treatments prior to that time can be put in perspective.

1.10 Chapter 6 sets out how the Government commissioned and funded research, setting the system for doing this in the context of its annual Public Expenditure Survey and outlining the roles of the Research Councils, the Neuropathogenesis Unit (NPU) and the Government Departments involved with BSE. It also describes how MAFF established and developed its programme of research into TSEs, and looks briefly at other TSE research programmes, including the Biology of the Spongiform Encephalopathies Programme (BSEP) set up by the Agricultural and Food Research Council (AFRC).

1.11 Finally, Chapter 7 contains a discussion on the conclusions that can be drawn about the scientific investigation of BSE. It also discusses shortcomings, identified with hindsight, in the BSE research programme and in the structures that were in place to deal with emergent diseases. The chapter concludes with lessons for the future for research management and coordination, for animal disease surveillance, and for the investigation of potential zoonoses.

1.12 In addition, this volume contains a Glossary of scientific terms and a Who's who of some of the players in the BSE story who appear in other volumes of the Report.