Brandy Weathers
Cluster 7: Biomedical Sciences
History and Cases of Prion Diseases
Abstract
The infectious agent of prion diseases affect large quantities of the mammalian species. The
demographic correlation between epidemics and specific cultural practices that deviate from the
norms of these species prompt prion diseases to fall under acquired,familial ,and sporadic
cases.To categorize the causes of prion diseases and identify their cases, the investigative process
utilizes documentations of historical sparks of epidemics involving prion diseases. Through
discussing prion outbreaks in history, I will analyze the basis for each and place them within
iatrogenic, familial, and sporadic cases. Through identification of each involved in epidemics of
these infectious diseases, the cases lead to a resolution of the inquiry as to whether the infectious
agent comes from a viral infection or a genetic mutation.
Introduction
Prion diseases belong to a class of progressive neurodegenerative diseases called the
transmissible spongiform encephalopathies (TSEs). This infectious agent cause rare, yet dramatic
epidemics that affect remote populations by the thousands. The diseases can be obtained through
a genetic mutation,infectious agent, or unsystematically. These fall under familial,acquired, and
sporadic cases(Baker,Ridely 1996). The acquired case was the most common way to become
infected with the infectious agent, PrPsc(Prion Protein Scrapie1) . An animal can gain possession
of this agent by ingesting or absorbing a minimal dose of the transmittable agent. It is rarely seen
today, however, modern ways of obtaining an iatrogenic case of a prion disease is through
hospital contamination correlated with head surgery such as human pituitary-derived growth
hormones(Baker,Ridely 1996). Because of the external environmental contamination , the host
body becomes fatally infected . This supports the hypothesis that prion diseases are a viral
infection. Another case of obtaining a prion disease is known as Familial. This occurs in 15% of
human cases where one member of a family is infected. Due to the autosomal dominant pattern
of the disease, it typically occurs in one familial pedigree. This linkage in the disease was
1
Scrapie: The infectious prion agent that is developed in animals, typically sheep
Weathers, Brandy
correlated with the hypothesis that it could have occurred through a mutation in the PrP gene ,
thus making the epidemic of prions, a genetic matter(AJHG,2001). Lastly, the sporadic case is
one of the most unexplained ways of obtaining a prion disease. An organism does not have to be
infected or have the disease within their family pedigree in order to gain possession of this
disease.The unresolved debate arguing whether the prion disease comes from genetics or viral
infection expands with evidence from historical prion epidemics that support both hypotheses.
To gradually dissipate these debates and resolve the dichotomy, the ways that the prion disease
was obtained in history is classified into cases of acquired , familial, and sporadic(Baker,Ridely
1996).
Kuru
The neurodegenerative disorder, Kuru,first emerged in the South Fore of Papua New
Guinea during the 1960s. This malady took the lives of over one thousand victims,
predominantly the female,juvenile, and elderly population(Ahmad) This is due to ritualistic
maternal participation in the dismemberment of a deceased body. During this time , it was the
maternal kin that was initially in charge of removing the muscle, limbs, brains and internal
organs from a fresh corpse. Since the fat of the deceased body resembled the edible portions of
pork, it was utilized to keep the women, children, and elderly nourished(Bindon). This mortuary
cannibalism caused problems when the deceased brain was infected with the prion disease. It
became the initial reason for the destruction of the South Fore, New Guinea population and the
rapid spread of the fatal infectious agent. This disease is classified under an acquired case due to
the ingestion of infected nervous tissue. An observation of the Kuru disease in the South Fore
village ,conducted by John Matthews in 1971, supported the hypothesis for a viral infection and
refuted the genetic hypothesis. He asserted that the disease was too common and too lethal to
Weathers, Brandy
occur genetically , unless,hypothetically, a balanced mechanism of polymorphism took place, but
there is no evidence to support that assumption(Lindenbaum).
Bovine Spongiform Encephalopathy and Variant Creutzsfeldt-Jakob disease
Another epidemic belonging to an acquired case of the prion disease is Bovine
Spongiform Encephalopathy, also known as Mad Cow Disease. With 3500 documented cases per
month recorded, this epidemic wiped out multiple bovine species. Like the South Fore villagers
of New Guinea, the mistakable methods of handling carcasses were by producing sustenance out
of the freshly deceased bovine meat. As contaminated pellets were constantly produced for
consumption, the infectious agent had the most habitable environment to reproduce within the
mammalian cells due to the constant ingestion of the scrapie prion agent2(Baker,Ridely 1996).
The disease was contained by banning the corrupted methods of food production in 1988, but the
threat of the agent was still eminent as the incubation period lasted decades. The disease quickly
approached humans in 1982 through human consumption of contaminated beef. When a burger
is created - if the infected brain stem and the spinal cord is utilized within the meat- the infected
prion agent from the nerve tissue does not decompose. As it makes its way from the
gastrointestinal tract, to the blood stream , then to the brain, the human organism that is infected
obtains a transmissible spongiform encephalopathy ( TSE) called variant Creutzfeldt-Jakob
disease(vCJD), another acquired form of prion disease that is also incurable and
fatal(Baker,Ridely 1996).
Weathers, Brandy
This form of the infectious agent falls under the hypothesis of a viral infection due to its lack of
nucleic acids. However, it contains characteristics unusual to viruses and bacteria; the agent is
difficult to kill and can have an incubation period of about 50 years before symptoms emerge.
While it is inferred that variant Creutzfeldt-Jakob disorder is a prion disease, it is incredibly
inexplicable and a fairly recent topic of study. Scientists do not have a treatment or cure for the
recently emerged disease(Baker,Ridely 1996).
Sporadic CJD and Sporadic Fatal Insomnia
Creutzfeldt-Jakob disease is remarkably flexible as it has more than one way a human
species can obtain the infectious prion agent. Though it was more common among the united
states for a human to gain the disease by acquiring the infectious agent back in the 1980s, there
are also sporadic and familial cases of CJD that can occur more often in humans today. Sporadic
CJD, the most common case of the prion disease today, occurs in people between the ages of 40
and 60. There is no known risk factor for the disease , therefore it cannot be predetermined. The
disease becomes more rapid and eventually lethal a few months after symptoms of imbalance,
memory loss, anxiety , and depression begin to erupt(UCSF Memory and Aging Center). This
form of prion disease categorizes itself within a genetic hypothesis because there are no known
environmental causes for sCJD to strike. The source of the disease -and the reason it is classified
under a sporadic case- is because of an erratically infectious sequence that can materialize in a
prion production pattern. The sporadic case of CJD refutes the hypothesis that prions are caused
by viral infection because the virus would be obtainable form an external origin. Another disease
sparked by prions that supports the hypothesis of genetic involvement is sporadic Fatal Insomnia.
Like sCJD, it is a disorder that occurs from a rapid protein misfold and has no known risk factor
or environmental cause(UCSF Memory and Aging Center). It is eminently fatal and only takes
Weathers, Brandy
about 12 to 18 months before it causes death(Blitz 2015) . Both Creutzfeldt-Jackob Disease and
Fatal Insomnia are some of the most common sporadic neurodegenerative disorders that take
place today , yet they have the most unexplained methodology ; making prion diseases one of the
most mysterious phenomenons since the 1700s.
Gerstmann-Sträussler-Scheinker Syndrome (GSS)
Lastly, neurodegenerative disease, GSS,belongs to a familial case of prion diseases. The
infected gene is autosomal dominant and only needs one affected parent for the offspring to
obtain the infectious agent. However, the disease can also occur from a new mutation; an
individual can obtain the infectious agent sporadically from a gene mutation and transfer it to
their offspring, also(Office of Rare Disease Research). The genetic mutation begins to affect
their human host when they are around 40 and becomes fatal within 5 years. It was first
discovered in 1936 by Josef Gertsmann , Ernest Straussler, and Ilya Scheinker, though it has
been hard to track due to how rarely it occurs. The first documented case was in 1989 when the
prion mutation was recognized in a familial pedigree. The disease can be diagnosed by typical
symptoms of neurodegenerative illnesses, including nystagmus, which is a rapid eye movement
in a single direction and begins to slowly return to its original position(Gambetti,MD). GSS
supports the hypothesis for genetic prion involvement due to the lack of external environmental
stimulus. The disease could be tracked through a pedigree of families, exposing the disease as a
genetically transferrable nucleic acid.
Conclusion:
Exploring the disorders caused by Prions, it can be inferred that the diseases infect
populations by methods that could be categorized into three cases. Throughout history, the most
common case of receiving the disease went from being acquired in the late 1900s to sporadic in
Weathers, Brandy
today’s era because of the regulations put on food and changes in cultural practices. While the
internal methods of prions within the body are still an open debate , it can be seen throughout
history that prion diseases have the ability to conquer their hosts genetically and virally.This
could possibly answer or hinder the pending dichotomy of whether the prion infections are
sparked genetically or virally.
Weathers, Brandy
Bibliography
Ahmad, Shamim I. "Kuru." Neurodegenerative Diseases. New York: Landes Bioscience, 2012.
143-53. Print.
Baker, Harry F., and Rosalind M. Ridley. "The Paradox of Prion Disease." Prion Diseases.
Totowa, NJ: Humana, 1996. 1-14. Print.
Bindon, Jim. "Kuru: The Dynamics of a Prion Disease." Kuru: The Dynamics of a Prion
Disease. University of Alabama, n.d. Web. 27 July 2015.
Blitz, Matt. "Fatal Familial Insomnia: The Brain Disease That Stops You Sleeping." Fatal
Familial Insomnia: The Brain Disease That Stops You Sleeping. Gizmodo, 03 Apr. 2015. Web.
27 July 2015.
"Creutzfeldt-Jakob Disease (CJD)." Types of Prion Disease. UCSF Memory and Aging Center,
2015. Web. 27 July 2015.
Gambetti, Pierluigi, MD. "Gerstmann-Sträussler-Scheinker Disease - Brain Spinal Cord and
Nerve Disorders." Merck Manuals Consumer Version. Merk Manual, n.d. Web. 27 July 2015.
"Gerstmann-Straussler-Scheinker Disease." Gerstmann-Straussler-Scheinker Disease | Disease |
Overview | Office of Rare Diseases Research (ORDR-NCATS). National Center for Translational
Sciences, 22 July 2013. Web. 27 July 2015.
Lindenbaum, Shirley. “Understanding Kuru: The Contribution of Anthropology and Medicine.”
Philosophical Transactions of the Royal Society B: Biological Sciences 363.1510 (2008): 3715–
3720. PMC. Web. 27 July 2015.
Prusiner, Stanley B., Richard C. Moore, Fengqing Xiang, Jeffery Monaghan, and Dong Han.
"Huntington Disease Phenocopy Is a Familial Prion Disease." American Journal of Human
Diseases 69.6 (2001): 1385-388. Science Direct. Web. 20 July 2015.