In 1982 Stanley Prusiner introduced the term “Prion” to describe a new kind of infectious agent formed from proteins. His hypothesis that diseases such as scrapie, BSE and CJD are spread by prions rather than a virus was met with extreme incredulity for more than a decade. In the 1990s he was proven right and his work brought him the Nobel Prize for medicine in 1997. His story is our most recent example yet of a scientist in the category of “crackpots” who were right.
Born in 1942 in Iowa, Stanley Prusiner followed a typical American education and graduated as a medical practitioner from the University of Pennsylvania. Already he was considering a career in biomedical research and after his internship he took up a residency in neurology. In 1972 he cared for a woman dying of Creutzfeldt-Jakob disease (CJD), a neurological disorder that was then attributed to the effects of a “slow virus” despite the observation that it evoked no response from the body’s immune system. Prusiner was struck with a keen interest in the unusual characteristics of CJD and its apparent relatives such as scrapie in sheep. In 1974 he set up a laboratory to study the diseases but funding was difficult to obtain because a number of very expensive programs to find the infectious agent had already failed. Prusiner persisted and was able to gain some NIH funding on the back of other work as well as some private sources.
When Prusiner and his co-workers sought to purify and isolate the agent transmitting the disease, all they could find was proteins. They had expected to see nucleic acids that would point to a virus but no trace could be found. In 1982 Prusiner published a manuscript in which he introduced the idea of a new type of infectious agent that he called prions to explain the lack of a virus.
At the time it was widely accepted that all infectious diseases were spread by a limited number of well-known types of infection that included bacteria, fungi and viruses. The power of the existing paradigm was so strong that other researchers could not admit the possibility of another cause despite the evidence that something very different was at work. Other researchers working on the same problem were very critical. Prusiner described the reaction in his Nobel autobiography:
“As the data for a protein and the absence of a nucleic acid in the scrapie agent accumulated, I grew more confident that my findings were not artifacts and decided to summarize that work in an article that was eventually published in the spring of 1982. Publication of this manuscript, in which I introduced the term “prion”, set off a firestorm. Virologists were generally incredulous and some investigators working on scrapie and CJD were irate. The term prion derived from protein and infectious provided a challenge to find the nucleic acid of the putative “scrapie virus.” Should such a nucleic acid be found, then the word prion would disappear! Despite the strong convictions of many, no nucleic acid was found; in fact, it is probably fair to state that Detlev Riesner and I looked more vigorously for the nucleic acid than anyone else.
While it is quite reasonable for scientists to be skeptical of new ideas that do not fit within the accepted realm of scientific knowledge, the best science often emerges from situations where results carefully obtained do not fit within the accepted paradigms. At times the press became involved since the media provided the naysayers with a means to vent their frustration at not being able to find the cherished nucleic acid that they were so sure must exist. Since the press was usually unable to understand the scientific arguments and they are usually keen to write about any controversy, the personal attacks of the naysayers at times became very vicious.”
Within a few years a new form of the disease in cattle known as “Mad Cow disease” was spreading rapidly with farmers in the UK most severely hit. Despite the lack of understanding of how the infection could be spread it was claimed that humans could not contract it from eating tainted beef. This was proven wrong when people who had eaten poor quality meat were struck down by CJD. With a growing fear that many more people would be struck by the infection, more funding for research became available and by the 1990s it was generally accepted that Prusiner had been right.
Today a better understanding of prions is being developed. It is now thought that they propagate by refolding incorrectly into a structure that is able to convert normal protein molecules to the abnormal form. Even now a small minority cling to the belief that there must be a virus involved and continue to attack the prion hypothesis. In today’s science, old paradigms die hard just as they have done for centuries.