§ The Countess of Marasked Her Majesty's Government:
Whether they have established:
in order to satisfy Koch's postulates that the agent has jumped species from cattle to man, and whether these postulates have been satisfied in the case of the sheep scrapie agent passing to cattle.
- (i) that the BSE agent is present in every case of the disease, shown by isolation in pure culture;
- (ii) that the BSE agent is not found in cases of other disease;
- (iii) that once isolated, the BSE agent is capable of reproducing the disease in experimental animals; and
- (iv) that the BSE agent has been recovered from the experimental disease produced,
Lord LucasKoch's postulates relate to the classical criteria to establish that an agent is the unique cause of a disease and were established at a time when conventional bacteria were the only known infectious agents. Viruses were unknown and the criteria as set out in this question cannot be met in full even in relation to disease caused by conventional viruses, e.g. as viruses cannot be isolated from pure culture because they can only reproduce in living cells.
In the case of BSE the agent is not a bacterium nor, it is believed, a conventional virus. The disease agent cannot be isolated and grown in culture. Postulate (i) cannot therefore be met. What has been established is that, in every case of BSE which has been studied, the samples of brain from infected cattle always show a consistent pattern of incubation periods and lesion profiles when inoculated into a panel of mice of different genotypes. In other words whatever is in the brains of these cattle which causes disease always exhibits the same characteristic fingerprint in the mouse panel. This is true for cattle tested in the system not only from the UK but also from Switzerland.
On (ii), the agent has not been found in association with any other disease.
On (iii), brain material can be shown to transmit disease experimentally into cattle, mice, goats, sheep, pigs, mink and marmosets. With the exception of marmosets and mink, which have not been tested in the mouse panel, and of sheep, where the genetic make up of the sheep determines the outcome, the brain from animals experimentally infected with BSE always shows the same characteristic pattern as BSE when subsequently inoculated into the same panel of mice. This is also true of field isolates of brain tissue from cats, greater kudu and nyala which were believed to have been exposed to BSE agent through food and which developed an SE disease. In sheep one form of the gene results in the same classical BSE pattern as brain from other species when further transmitted into the mouse panel; another form of the gene results in a different pattern but this could be due to infection with natural sheep scrapie in the flock. The results for sheep seem to be related to the strong genetic component in 98WA susceptibility of sheep to the natural sheep disease scrapie.
The answer to (iv) is therefore yes in relation to brain tissue from all species tested except for some sheep.
In relation to disease in man it is not possible to carry out experimental exposure to BSE agent. Tissue from patients who died from both the old and new variants of CID has been injected into the same panel of mice but these tests take up to two years to do and are still under way.
In relation to sheep scrapie, none of the strains tested show the same characteristic pattern in mice as BSE. This may be a reflection of the fact that in scrapie the characteristics of the disease developed by an animal after experimental infection relates not simply to the strain of scrapie you put into the animal, but also to the species of animal and in some cases to the genotype within the species of the animal.