Volume 1: Findings and Conclusions
1. Introduction
Transmissible Spongiform Encephalopathies

50 Our Terms of Reference speak of two diseases: BSE, a disease of cattle; and variant CJD, a human disease. These are varieties from a rare group of diseases known as Transmissible Spongiform Encephalopathies (TSEs). TSEs cause the appearance of microscopic holes in the brain, giving it a sponge-like appearance - hence the term 'spongiform'. They are invariably fatal and affect both humans and animals. In 1986 a number of TSEs had been identified both in animals - scrapie in sheep and goats, Chronic Wasting Disease (CWD) in wild deer in North America and Transmissible Mink Encephalopathy (TME); and in humans - Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler Syndrome (GSS), kuru and Fatal Familial Insomnia (FFI). Although a signal feature of these diseases is that they are transmissible in the manner described in paragraph 52 below, they can occur, at least in humans and probably in other species, as a result of a genetic mutation that is inherited or, in some cases, that may arise spontaneously.

51 When BSE was first identified, the nature of the infectious agents causing TSEs was a matter of controversy. It was known that the agents were extremely difficult to inactivate - they could withstand treatments commonly used to disinfect virus-contaminated materials - and that researchers had failed to detect an immune response in hosts to their presence in a variety of experiments. Although these features suggested that TSEs were not caused by conventional viruses, some believed that they must be caused by an unconventional virus. This belief was challenged by those who thought that TSEs were transmitted as a result of a reaction between proteins. This theory has now won general, though not universal, acceptance.

52 How, under this theory, does transmission of these diseases occur? Let us take BSE as an example. The building blocks of every animal, including the human animal, are proteins. These are minute particles which have different chemical compositions. BSE involves the deformation of one of these proteins (prion protein) ¹ in very large numbers within the brain of the cow, until the brain develops a spongy appearance and is fatally damaged. The same deformation of this protein takes place in other specific tissues in the cow. If some of the deformed proteins of an animal suffering from BSE are introduced into the body of another animal or into a human ('the host'), they may induce similar proteins that are found in the host to deform in the same way. By a kind of chain reaction, deformation of these proteins may spread to and within the brain of the host, until finally the brain is so damaged that the host is taken ill and dies.

53 The prion protein exists in its normal form in all animals, but its chemical composition is not precisely the same in each. It can even have slight variations in animals of the same species as a result of minor variations of the prion gene. The more similar the prion protein in infected animals to that in the host animal, the easier the transmission of a TSE appears to be. Thus transmission is easiest between animals of the same species. When the animals are of different species, the 'species barrier' will sometimes prevent transmission altogether.

54 The obvious way in which deformed protein from an animal incubating a TSE may be introduced into another animal is as food. There are, however, other possibilities. For instance, medical products administered by injection are sometimes derived from animal tissues or fluids. Experiments have shown that it is very much easier to transmit a TSE to an animal by injecting infected tissue directly into the brain than by feeding it to the animal. A minute quantity will suffice for such intracerebral transmission; indeed CJD has sometimes been transmitted on surgical instruments used in neuro-surgery despite their sterilisation.