From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 120
In 1975, when Lewis Thomas, physician, scientist and medical writer, was asked to make
a list of the Seven Wonders of the Modern World, he chose scrapie disease, now known
to be caused by a proteinaceous infectious particle (prion), as number four.1 To quote
Thomas, “The scrapie agent seems the strangest thing in all biology.” His reason was that
the disease can propagate from a few infectious units to billions in just one year despite
the absence of DNA or RNA. Without DNA or RNA, there was a serious question regard-
ing the mode with which the agent replicated and survived. Prions, which even in 1975
showed evidence of being all protein, appeared to violate the central dogma of molecular
biology: genetic information flows from nucleic acids to proteins.2
Even though 35 years have passed since Thomas’ list was first published, and he is
no longer living, prions remain one of nature’s wonders. In the past three decades, no
hypothesis has been proven to explain the protein-only composition of prions, their chem-
ical composition and the mechanism for their formation in the neurons of infected hosts.3
This chapter reviews the major prion diseases, regulatory matters pertaining to
animal tissues and sterilization methods. Despite the progression of science, prions still
present a biological conundrum and the risk to humans remains uncertain.
History
Prions entered the scientific lexicon in 1982, courtesy of Stanley Prusiner, a neurologist at
the University of California at San Francisco. He was working on some esoteric maladies
that were known as “slow virus” diseases. Prusiner told the scientific community that they
were caused by prions, a term he coined by blending “protein” and “infection.” (Logically,
the word should have been proin, but Prusiner, with melodious intent, transposed the “o”
and the “i” to make it more terrific.4) Prion diseases, however, were noted much earlier.
The earliest written record of scrapie in English sheep first appeared in the 1730s,
but the disease was already prevalent in central Europe. A kuru outbreak occurred in
the 1950s, which was observed only among the highland tribes in New Guinea. In 1959,
William J. Hadlow of the Rocky Mountain Laboratory of the National Institute of Allergy
and Infectious Diseases suggested that scrapie and kuru might be related. However, it was
not until the 1960s that scientists experimentally transmitted kuru to chimpanzees. This
demonstrated the transmissible nature of prion diseases. Crueutzfeldt-Jakob disease was
first described in the early 1920s and classified with other degenerative brain diseases the
infectious nature of CJD was not established until 1928.
Diseases
As mentioned above, prions are unconventional infectious agents that cause rare but fatal
neurological illnesses such as scrapie, kuru, Creutzfeldt-Jakob disease and bovine spongi-
form encephalopathy.
Scrapie, the disease listed by Thomas, is an infectious, neurodegenerative disorder
affecting the central nervous system (CNS) of sheep. (The name scrapie comes from the
tendency of afflicted sheep to scrape off much of their wool.) It is a close cousin to bovine
spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervids (deer fam-
ily), as well as kuru, fatal and sporadic familial insomnia, Gerstmann-Straussler syndrome
and Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) in humans. Each is a brain
disease marked exclusively by a deposition of prions in the CNS.5
A unique feature of these diseases is that they can have three different origins:
sporadic, inherited and infectious. The clinical epidemiological and neuropathological
features can be very different, but they are classified together because the key molecular
event appears to be the same: a misfolding of the prion protein. The damage is thought to
occur when abnormal prion protein (PrPSc) molecules gain access to the brain and cause
normal prion protein to change shape to the abnormal form. (Normal prion protein (PrPc)
is encoded by a gene on human chromosome 20, is expressed in the brain, and in its normal
In 1975, when Lewis Thomas, physician, scientist and medical writer, was asked to make
a list of the Seven Wonders of the Modern World, he chose scrapie disease, now known
to be caused by a proteinaceous infectious particle (prion), as number four.1 To quote
Thomas, “The scrapie agent seems the strangest thing in all biology.” His reason was that
the disease can propagate from a few infectious units to billions in just one year despite
the absence of DNA or RNA. Without DNA or RNA, there was a serious question regard-
ing the mode with which the agent replicated and survived. Prions, which even in 1975
showed evidence of being all protein, appeared to violate the central dogma of molecular
biology: genetic information flows from nucleic acids to proteins.2
Even though 35 years have passed since Thomas’ list was first published, and he is
no longer living, prions remain one of nature’s wonders. In the past three decades, no
hypothesis has been proven to explain the protein-only composition of prions, their chem-
ical composition and the mechanism for their formation in the neurons of infected hosts.3
This chapter reviews the major prion diseases, regulatory matters pertaining to
animal tissues and sterilization methods. Despite the progression of science, prions still
present a biological conundrum and the risk to humans remains uncertain.
History
Prions entered the scientific lexicon in 1982, courtesy of Stanley Prusiner, a neurologist at
the University of California at San Francisco. He was working on some esoteric maladies
that were known as “slow virus” diseases. Prusiner told the scientific community that they
were caused by prions, a term he coined by blending “protein” and “infection.” (Logically,
the word should have been proin, but Prusiner, with melodious intent, transposed the “o”
and the “i” to make it more terrific.4) Prion diseases, however, were noted much earlier.
The earliest written record of scrapie in English sheep first appeared in the 1730s,
but the disease was already prevalent in central Europe. A kuru outbreak occurred in
the 1950s, which was observed only among the highland tribes in New Guinea. In 1959,
William J. Hadlow of the Rocky Mountain Laboratory of the National Institute of Allergy
and Infectious Diseases suggested that scrapie and kuru might be related. However, it was
not until the 1960s that scientists experimentally transmitted kuru to chimpanzees. This
demonstrated the transmissible nature of prion diseases. Crueutzfeldt-Jakob disease was
first described in the early 1920s and classified with other degenerative brain diseases the
infectious nature of CJD was not established until 1928.
Diseases
As mentioned above, prions are unconventional infectious agents that cause rare but fatal
neurological illnesses such as scrapie, kuru, Creutzfeldt-Jakob disease and bovine spongi-
form encephalopathy.
Scrapie, the disease listed by Thomas, is an infectious, neurodegenerative disorder
affecting the central nervous system (CNS) of sheep. (The name scrapie comes from the
tendency of afflicted sheep to scrape off much of their wool.) It is a close cousin to bovine
spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervids (deer fam-
ily), as well as kuru, fatal and sporadic familial insomnia, Gerstmann-Straussler syndrome
and Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) in humans. Each is a brain
disease marked exclusively by a deposition of prions in the CNS.5
A unique feature of these diseases is that they can have three different origins:
sporadic, inherited and infectious. The clinical epidemiological and neuropathological
features can be very different, but they are classified together because the key molecular
event appears to be the same: a misfolding of the prion protein. The damage is thought to
occur when abnormal prion protein (PrPSc) molecules gain access to the brain and cause
normal prion protein to change shape to the abnormal form. (Normal prion protein (PrPc)
is encoded by a gene on human chromosome 20, is expressed in the brain, and in its normal