Anyone attending this lecture, or subsequently reading this monograph has likely already experienced the process of becoming an lycanthrope. It’s no secret that the process begins with a simple, or in some cases, not so simple, bite from another lycanthrope. What most of you do not know, is why a bite could cause such a transformation, and what exactly happened at and below the cellular level during your transformation.
Although legend holds that lycanthropy was spiritual or mystical in origin, advances in medical knowledge, starting with Leeuwenhoek in the late 1600’s, and continuing with Pasteur, Koch, and Ivanovsky in the late 1800’s, raised the suspicion that the causative agent of the transformation was a microscopic disease organism: perhaps a bacterium or virus. The difficulty with that theory was our inability to isolate the agent using known techniques for those kinds of organisms. Also, normal disinfection techniques proved ineffective for preventing the transmission of the presumed disease. Investigators found early on, that most of the lore concerning how the condition was propagated was inaccurate. The only proven method for creating a new lycanthrope was, and until this past year remained, having the candidate be bitten by an existing lycanthrope.
Research in this area took an exciting turn in 1982, with the publication of a number of papers in the human medical world, concerning a newly-named type of infectious agent, called the prion. The word prion is a portmanteau of the phrase ‘proteinaceous infectious particle’, and was coined by the human researcher Stanley Prusiner at that time. The existence of prions had been suspected by other researchers as early as 1962, but the concept hadn’t been named. Prusiner and others succeeded in isolating prions associated with the sheep disease ‘scrapie’ in the early 1980’s, and since that time a number of other animal and human diseases have been found to have prions as causative agents. Most notable are the spongiform encephalopathies Creutzfeldt-Jakob and kuru, found in humans, BSE (Mad Cow Disease) in cattle, and TSE (Chronic Wasting Disease) in deer and other animals.
The ‘discovery’, or rather proof of existence, of prions made a new line of inquiry available to our researchers, who immediately adapted the techniques used by Prusiner and others to attempt to recover prions from a group of volunteers of our kind. These early attempts failed, for the most part, except when samples were taken from the volunteers’ salivary glands. Further clinical studies, where human volunteers, mostly comprised of close family members of existing lycanthropes, were given subcutaneous injections of various body fluids from the lycanthrope volunteers, indicated that the infective agent was present only in the vector’s saliva, as well.
The correlation is obvious, and the lack of infective activity of samples from other parts of the body explains at least one other mystery: i.e., why individuals are never born as lycanthropes. Our kind are known to be a fertile, and to procreate as easily as humans - even with humans - but there has only been one case in our entire history where a newborn in a pack was not born fully human! Even in that case, which was documented in the year 1053, it was known that the mother was already pregnant and in her second trimester, when she was transformed. I is obvious that the foetus was simply infected concurrently with the mother.
The question of how an infective agent confined to the salivary glands can be responsible for the observed physiological effects of infection remained open, however. In order to answer this question, it was necessary to undertake a large array of tissue culture and biochemical studies. Our findings from these studies are the main topic of this presentation.
In-vitro serum studies disclosed that free prions could and did interact with blood proteins and convert them into more prions, regardless of the original concentration of prions. Somatic tissue culture studies, on the other hand, disclosed that the infectivity of the prions decreased as the the saliva samples became more and more diluted. This was not an artifact due to the lowered availability of infective particles. It was observed in subsequent studies of infected tissue, using an electron microscope, that on contact with the tissue, some of the prions became bound with structural proteins forming the somatic cells, and were no longer infective; and that as the actual saliva samples became more dilute, more of those bindings occurred. This implied that some agent present in the saliva was responsible for preserving the infectivity of the prions.