- v -

Section 1
- 1 -
1 Introduction
Bovine spongiform encephalopathy (BSE) is a disease of cattle that was first documented
in the United Kingdom in 1986.  It has since spread to several countries in Europe, and most
recently to Japan.  The disease causes the degeneration of central nervous system (CNS) function,
ultimately leading to death in all cases.  Perhaps more worrisome is the possibility that meat
products contaminated with BSE infectivity can cause a human form of this illness, known as
1
variant Creutzfeldt-Jakob Disease, or vCJD.  Like BSE, vCJD causes CNS degeneration and is
always fatal.  Unlike many other animal-borne diseases, the agent thought to be responsible for
BSE and possibly vCJD is at least partially resistant to destruction by standard cooking practices,
sterilization procedures, and processes used to recycle bovine protein prior to its use as a feed
supplement.  For that reason, the presence of BSE can lead to the spread of disease among other
animals, and potential health risks for people.
Although there has never been a case of BSE documented in the United States, the
potential for the disease to spread, and the potential threat it poses to people if it were to arise has
raised concern in this country.  In order to better characterize the nature of these risks, the United
States Department of Agriculture (USDA) commissioned the Harvard Center for Risk Analysis to
conduct a study of BSE in the U.S.
This study was undertaken to investigate potential pathways by which BSE or other TSEs
could arise in the United States (U.S.) cattle population .  In particular, the analysis describes the
2
use of a quantitative simulation model that characterizes how the introduction of BSE would
affect animal health over time, and the extent to which it could result in human exposure to
contaminated food products.  The ability of this model to quantify various aspects of the disease’s
progression (e.g., number of animals infected over time, quantity of the transmissible agent in
food presented for human consumption) distinguishes it from other efforts to characterize BSE
risk, such as the European Union’s Scientific Steering Committee report on the Geographical
Risk of Bovine Spongiform Encephalopathy (SSC 2000).  We have used the simulation model to
1
Although the exact etiology of BSE is uncertain, in many respects the transmission of the disease can be
evaluated as though it arises from an infectious agent. Because the nature of the agent is still a matter of
some scientific debate, we use the term “infectivity” to characterize materials that can transmit the disease
from one animal to another or potentially from animals to people.
2
For the purpose of the study, “other TSEs” are defined to be naturally occurring animal prion diseases that
if present in cattle, will manifest with clinical and histopathological characteristics that are similar to those

Section 1
- 2 -
determine the impact of possible past introductions of BSE into the US, to identify those risk
management control options that most influence the spread of disease, and to identify those
sources of uncertainty that have the greatest impact on our results.  This information can be used
to help identify the most promising control measures and to prioritize data collection and research
efforts.
The analysis is not a complete human health risk assessment in two respects.  First, we do
not quantify the probability that BSE will be introduced into the U.S.  Hence, all our risk
estimates are conditional on hypothetical scenarios.  Second, although we quantify potential
human exposure to BSE-contaminated food products, we do not estimate how many people will
contract variant Creutzfeldt-Jakob Disease (vCJD).  We have omitted quantitative treatment of
both of these issues because the available information is inadequate.
The remainder of this study is organized as follows.  Section 2 first describes the different
types of TSEs, their characteristics, theories as to the origin of the BSE epidemic in the UK, and
measures taken to control the spread of BSE. Next, pathways for the introduction of disease are
discussed in further detail, including the potential for spontaneous development of BSE,
transmission from another species in the U.S. with a prion disease, importation of BSE-infected
cattle, or use of cattle rations that may contain contaminated material.  Section 3 describes our
methodology, including the simulation model used in this analysis and the specific scenarios
evaluated.  Section 4 summarizes our results, and concludes with a discussion of our findings.
associated with cattle BSE.  For the remainder of this document, the term “BSE” will collectively refer to
BSE and to these other TSEs.

Section 2
- 3 -
2 Background
This section provides background for the analysis described in this report.  Section 2.1
outlines the characteristics of transmissible spongiform encephalopathies (TSEs), the class of
diseases to which BSE belongs.  Section 2.2 reviews the hypotheses advanced for the origin of
the BSE epidemic in the UK.  Section 2.3 describes potential pathways by which BSE could be
introduced into the U.S.  Finally, Section 4 reviews regulatory actions taken by governments
around the world to slow the spread of this disease.
2.1
Overview of Transmissible Spongiform Encephalopathies (TSEs)
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a
family of rare, slowly progressive, and uniformly fatal neurodegenerative disorders that affect
humans and animals.  All of these diseases have incubation periods of months to years between
infection and the onset of clinical signs.  The prevailing hypothesis is that these diseases are
caused by novel agents called prions.  In humans, prion diseases may present as genetic,
infectious, or sporadic disorders, and all involve the modification of the prion protein.  Known
TSEs include:
•
Creuzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Straüssler-Sckeinker (GSS),
and Fatal Familial Insomnia (FFI) in humans;
•
Scrapie in sheep and goats;
•
Transmissible Mink Encephalopathy (TME) in mink;
•
Chronic Wasting Disease (CWD) of deer and elk; and
•
Bovine Spongiform Encephalopathy (BSE) in cattle.
Other examples, such as Feline Spongiform Encephalopathy (FSE), are thought to be the result of
cross-species transmission of a TSE (BSE in the case of FSE).  Variant CJD (vCJD) is a newly
discovered TSE of humans and is likely the result of exposure to the BSE agent.
The first records of TSEs date back to the early 18 century (Stockman, 1913, Brown and
th
Bradley, 1998), with the mention of scrapie in sheep.  The name of the disease reflects its
associated clinical signs, including the tendency of the sheep to scrape off their wool on fences or

Section 2
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other objects.  Experimental transmission of scrapie to other species, such as mice and goats,
demonstrated that the disease was transmissible and had a very long incubation period (Cullie and
Chelle, 1936, Cullie and Celle, 1939, Pattison et al., 1959).
During the 1950s, many scientists became interested in Kuru, a fatal disease that affected
the Fore population of Papua, New Guinea.  Kuru is  characterized by neurologic signs and
neuropathologic changes similar to those of scrapie (Zigas and Gajdusek, 1957, Klatzo et al.,
1957, Alpers, 1970).  These similarities were pointed out by Hadlow in 1959, who suggested that
Kuru might also be transmissible to other animals (Hadlow, 1959).  Subsequently, Gadujsek and
his colleagues succeeded in transmitting Kuru to chimpanzees (Gajdusek et al., 1966).  This
experiment supported the hypothesis that Kuru is transmitted by an infectious mechanism (i.e.,
ritualistic cannibalism).  Later, other spongiform encephalopathies were found to be
transmissible, including CJD, FFI, TME, CWD, and BSE.  To date, most of the experimental data
on TSEs comes from studies of CJD and scrapie.  More recently, BSE has become an area of
active research.
The specific agent responsible for TSE diseases has not been identified with certainty, but
the leading theory suggests that the etiologic agent is an abnormally configured protein normally
encoded by the host (prion protein or PrP) (Bolton et al., 1982, Prusiner, 1982, Prusiner, 1994,
Prusiner, 1998).  Normal prion protein (PrP ) is soluble in detergents and has a predominantly
c
α
-
helical structure.  In contrast, abnormal PrP (PrP ) is insoluble in detergents, relatively resistant
sc
to proteases, and has a predominantly
β
-sheet secondary structure.  Although still a matter of
controversy, PrP
sc
appears to accumulate in an infected host and eventually cause disease (Bueler
et al., 1993, Manson et al., 1999, Hsiao et al., 1991, Telling et al., 1995, Hill et al., 2000).
Deposits of PrP
sc
in tissues are associated with the presence of transmissible infectivity
(McKinley et al., 1983).  Additionally, PrP
sc
is the only molecular marker specific for TSE
infections.  Spongiform degeneration, neuronal vacuolation, and gliosis appear to be associated
with abnormal PrP deposition.  Remarkably, TSE infection has been reported in the absence of
detectable PrP
sc
(Lasmezas et al., 1997) and PrP
sc
formed in vitro, by conversion of PrP , has not
c
yet produced disease in animal bioassays (Hill et al., 1999). The etiologic agent is not inactivated
by treatments that usually destroy bacteria and viruses (Kimberlin et al., 1983, Taylor, 1991b,
Taylor, 1991a, Taylor, 1993).  No immune response to the agent has been detected.

Section 2
- 5 -
An alternative hypothesis to the prion theory, referred to as the virino model, proposes
that the agent consists of a small nucleic acid that acts as an informational molecule, and that this
molecule is protected by the host PrP (Dickinson and Outram, 1988).  Despite several attempts
(Borras and Gibbs, 1986, Duguid et al., 1988), no exogenous nucleic acid has been identified in
experimental TSE.  The virino model suggests different genetic “strains” of the agent are
responsible for the phenotypic variability in the disease.  The protein only (prion) hypothesis
proposes that conformational isoforms of PrP are responsible for such variability.  Another theory
proposes that TSEs are caused by conventional viruses (Diringer et al., 1994, Manuelidis et al.,
1995).  However, no infection-specific nucleic acid has yet been detected.
The mechanisms by which infection occurs for most naturally occurring TSEs are
uncertain.  Different animal TSEs appear to be passed in part by lateral transmission and perhaps
by maternal transmission to offspring in natural settings.  The human spongiform
encephalopathies are considered to be either sporadic, inherited, or acquired by an infectious
mechanism (Masters et al., 1978, McLean et al., 1998, Hsiao and Prusiner, 1990, Brown et al.,
1994a, Will et al., 1996).  Finally, there is evidence that for some TSE diseases, susceptibility has
a genetic component (Poulter et al., 1992, Carlson et al., 1994, Hunter et al., 1996, Hunter, 1997,
Hunter et al., 1997a, Bossers et al., 1997, Goldmann et al., 1996).
The remainder of this section has three parts.  Section 2.1.1 discusses the means by which
TSEs are passed from one animal to another, and perhaps from animals to humans.  Section 2.1.2
introduces the concept of the “species barrier,” a phenomenon that makes passage of a TSE from
one species to another far less “efficient” (and hence less likely) than passage between animals of
the same species.  Finally, Section 2.1.3 discusses susceptibility, i.e., the tendency for some
animals to be more likely than others to become infected following exposure to the infective
agent.
2.1.1 Transmissibility
TSE diseases can be passed from an infected individual to others under only certain
conditions.  While the potential for natural transmission has been demonstrated only for some
TSEs, transmission in an experimental setting has been demonstrated for most.

Section 2
- 6 -
Transmission of a TSE disease from one human to another appears to be limited to cases
of “iatrogenic transmission,” associated with surgery, use of cadaveric hormones, and ritualistic
cannibalism. Iatrogenic transmission is the only known route of transmission for CJD.
Documented cases have involved the use of contaminated silver electrodes used for stereotactic
electroencephalography, the use of contaminated neurosurgical instruments (Collinge and Palmer,
1997), and the use of contaminated tissues in transplant procedures (cornea, dura mater).  The use
of contaminated hormones preparations (growth hormone or gonadotropin prepared from
cadaveric pituitary glands) has been linked to transmission of TSEs in humans.  Kuru has been
transmitted from person to person as the result of ritualistic cannibalism in the people of Papua,
New Guinea.  In this case, the most likely route of exposure was via ingestion, although
transdermal or mucous membrane exposure cannot be ruled out.
Transmission of TSE diseases from one animal to another of the same species in the
absence of experimental intervention has been extensively documented in the case of sheep-borne
scrapie (Hadlow et al., 1982).  The mechanism by which other sheep in the same flock become
infected appears to be associated with exposure to infected placenta (Race et al., 1998), although
other routes of exposure may also play a role in transmission.  In sheep, transmission has also
been linked to the use of vaccines (Gordon, 1939, Gordon, 1946, Gordon, 1959, Agrimi et al.,
1999).  Natural transmission has also been identified in CWD (Williams and Young, 1982).  In
the case of CWD, it has been postulated that transmission is caused by pasturing on ground
occupied by infected animals (Miller et al., 1998).  Presumably, some long-lived agent in the
environment can pass the disease between individuals (Skarphedinsson et al., 1994, Sigurdson,
1991).  Naturally occurring mutations capable of causing the disease have not been identified in
animals (Chesebro, 1999).
Several species and animal breeds have been used as experimental models for TSEs,
including mice, hamsters, and non-human primates.  Results from these experiments indicate that
natural (oral) transmission is substantially less efficient than transmission via intracerebral (i.c.)
injection, the procedure usually used for transmission in experimental models.  For example, in
the case of BSE, transmission via oral ingestion is as much as 100,000 times less efficient than
i.c. injection (for a review of the literature, see (SSC, 2000b)).  Experimental data using a TSE
mouse model indicate that intravenous injection produces disease five to seven times less
efficiently than i.c. injection (Brown et al., 1999).  Finally, intra-peritoneal (i.p.) administration of

Section 2
- 7 -
infectivity is estimated to be 100 times less efficient than i.c. transmission (Kimberlin and
Walker, 1988).
2.1.2
The Species Barrier
Interspecies transmission of TSEs is mitigated by a so called “species barrier”.  This
barrier represents the decreased efficiency with which TSEs are passed from one animal to a
second animal of a different species, compared with the efficiency with which the TSE is passed
among animals of the same species.  That is, a much greater amount of infective material is
necessary to infect an animal from a different species than is needed to pass the disease to an
animal of the same species.  The species barrier is also associated with an increase in the
disease’s incubation period (i.e., the delay between exposure to the agent resulting in infection
and the manifestation of disease).  In some instances the species barrier seems to confer complete
resistance to transmission.  It is at least conceptually possible that an animal failing to develop the
disease following cross species challenge would become infected if administered a sufficiently
large dose of infectivity, or would manifest clinical signs of disease if it somehow lived longer
than the incubation period associated with the species barrier (Hill et al., 2000).
Although transmission of a TSE from one species to another may be less efficient than
the transmission within the same species, once it occurs, the TSE may become “adapted” to the
new host.  Because it has adapted to the new species, it can be transmitted more efficiently among
members of that species, and the incubation period becomes shorter and less variable.  For
example, when scrapie is transmitted experimentally from one species to another, the incubation
period is usually longer in the first passage than that seen in subsequent passages within the new
species (Dickinson et al., 1976).
The species barrier probably reflects some combination of factors including differences
between the donor’s and recipient PrP.  Scrapie studies conducted in mice, rats, and hamsters
demonstrate the presence of a species barrier.  These findings include pathogenesis differences
between the first and subsequent passages in the new species, and how rapidly the transmitted
strain replicates in the new host (Kimberlin et al., 1987, Kimberlin and Walker, 1989), and others.
The response of some TSEs exhibits heterogeneity within a species, a characteristic that
appears to be due to the existence of different strains of the agent.  Strains are distinguished by

Section 2
- 8 -
highly replicable differences in the incubation period, neuropathology, and host range (Fraser and
Dickinson, 1968, Bruce et al., 1989).  CJD, scrapie, TME, and CWD show strain diversity, while
BSE appears to be a single, stable strain (Bruce et al., 1994, Bruce et al., 1997).  vCJD (i.e., the
new form of CJD related to exposure to the BSE agent) does not demonstrate morphologic strains
(Will et al., 1996, Hill et al., 1997, Bruce et al., 1997, Scott et al., 1999).
Recipient characteristics also affect the efficiency with which TSEs are transmitted
across species.  Some species, such as rabbits or chickens, do not develop disease when
challenged with specific TSEs, while other species do.  It has been postulated that the similarities
between the PrP structure between the donor and the recipient explain the differences in
transmission efficiency (Priola et al., 1994, Raymond et al., 2000).
Because the presence of a TSE agent is often assessed by inoculating a test species (e.g.,
mice) with the suspect material, the species barrier compromises the sensitivity of these
bioassays.  Cattle-to-cattle transmission of BSE by the intracerebral route is known to be 1,000
times more efficient than cattle-to-mouse transmission by the same route (MAFF, 2000b).  It is
often assumed that the species barrier decreases transmission efficiency by a factor of between 1
(no decrease) and 1,000 (Det Norske Veritas, 1997).  The assumption that the species barrier is 1
(i.e., that there is effectively no species barrier) is considered to be a worst-case scenario.  In an
opinion on the species barrier for transmission of BSE from cattle to humans, the EU Scientific
Steering Committee suggested that plausible values for the impact of the species barrier on
transmission efficiency range from between 1 and 100,000 (SSC, 1999a).  This range was later
updated to between 10 and 100,000 (SSC, 2000b).  However, the committee concluded that it is
impossible to estimate the true value for BSE species barrier between cattle and humans within an
order of magnitude given current knowledge (SSC, 2000b).
2.1.3 Susceptibility
“Susceptibility" refers to the likelihood of becoming infected following a specific
exposure to the infective agent.  Susceptibility to TSEs appears to depend on specific interactions
between the agent, the host, and the environment (e.g., animal age, PrP primary structure of the
host, PrP characteristics of the recipient animal, route of exposure, and dose of agent).

Section 2
- 9 -
Mutations and polymorphisms of the PrP gene are associated with many TSEs in humans,
sheep, mice, and possibly elk. Humans and sheep are the two species for which spongiform
encephalopathies apparently occur naturally and in which there are recognized genetic
components that predispose individuals to disease.  In the case of scrapie, there is evidence that
the disease does not develop spontaneously, but instead requires exposure to an infective agent
(Hunter et al., 1996, Hunter and Cairns, 1998).  In the case of human disease, studies conducted
using in transgenic mice that over express mutant PrP [P101L (corresponding to PrP P102L in
humans)] have shown that Gerstmann-Straüssler Skeinker might be a genetically induced illness
(Hsiao et al., 1991, Hsiao et al., 1994).  However, recent research using transgenic mice that are
normal expressers of mutant PrP failed to demonstrate development of the spontaneous TSE
(Manson et al., 1999), suggesting that the mutation may increase susceptibility to infection
(Weissmann and Aguzzi, 1999, Manson et al., 1999), rather than cause the disease on its own.  In
contrast, in cattle, susceptibility to BSE has not yet been shown to be associated with
polymorphism in the PrP gene (Hunter et al., 1994).
An important physiologic factor that is likely to affect susceptibility to infection is the
age of the animal.  For example, young cattle are estimated to be ten times more susceptible than
adults, with data well described by a model that assumes susceptibility declines exponentially
with an annual rate constant of 0.85 after the age of four months, with susceptibility ultimately
declining to 10% of its peak value (Koeijer et al., In press).  An alternative estimate computed by
back calculating a model of the UK BSE epidemic suggests that susceptibility peaks at 1.31 years
and decreases in the following years (Anderson et al., 1996).  Other investigators estimated that
susceptibility in cattle peaks between 0.5 to 1.5 years of age (Woolhouse and Anderson, 1997).
Age-related susceptibility is hypothesized to be associated with permeability of the intestine to
large proteins and with the development of the Peyer’s Patches (PP).  The PP seem to play a role
in the pathogenesis of the prion diseases and to influence the susceptibility of the animal to
infection.  For example, in sheep, the ileal PP are shown to be more active and to be largest when
the animal is around 2-3 months old and to disappear when the animal reaches an age of one and
one-half years (Griebel and Hein, 1996).  The appearance of the PP in sheep appears to coincide
with the period of greatest susceptibility of sheep to scrapie (Hadlow et al., 1982, Andreoletti et
al., 2000).
Age-related susceptibility may be an important factor in understanding BSE transmission
because potential exposure to BSE-contaminated feed (see Section 2.2 and Section <IP_ADDRESS> below)

Section 2
-
10 -
can also change with age.  The ages at which animals are exposed depends on when they receive
feed with protein supplements, something that may vary from country to country.  For instance,
Meat and Bone Meal (MBM) was used in the formulation of “least cost” calf starter rations in the
UK during the period of 1970-1988 (Horn et al., 2001), leading to BSE exposure when animals
are most susceptible to disease.
The remainder of this discussion addresses susceptibility issues specific to sheep,
humans, bovines, and cervids in turn.
Sheep
In sheep, polymorphisms identified at codon 136, 174 and 171 of the PrP gene play the
largest role in variations in the development of natural scrapie.  The clinical and pathological
variations of the disease are a direct result of host-agent interaction.  Holding both dose and route
of transmission fixed, the transmission of scrapie depends on the homology of the donor’s PrP
and the recipient’s PrP.  Some aspects of the pathogenesis can differ depending on the interaction
of agent strain, host genotype, route of infection, and dose of the agent.
Naturally infected sheep of a number of breeds in the US, UK, Europe, and Japan carry
valine at codon 136 (VV
136 or
VA
136
) or glutamine at codon 171 (QQ
171
) (Laplanche et al., 1993,
Westaway et al., 1994, Belt et al., 1995, Ikeda et al., 1995, Hunter et al., 1993, Hunter et al.,
1994) of the PrP gene.  There has only been one report of scrapie-affected Suffolk with arginine
homozygosity at codon 171(RR
171
) and four reports of scrapie affected Suffolk with
glutamine/arginine heterozygosity at codon 171 (QR
171
) (Ikeda et al., 1995, Hunter et al., 1997b).
Scrapie strains can be distinguished by biological parameters such as the incubation period, lesion
profile, and amyloid plaque production (Dickinson and Meikle, 1971, Dickinson and Outram,
1988, Bruce and Fraser, 1982, Bruce et al., 1991, Bruce et al., 1997).
There has been some debate as to whether naturally occurring scrapie is a purely
genetically-induced disease (Ridley and Baker, 1996) or if PrP genotype merely influences
susceptibility following exposure to an infectious agent.  The current consensus rules out the
hypothesis that scrapie is a purely genetic disease (Hunter and Cairns, 1998, Hunter, 1998) and
suggests that susceptibility and exposure are both necessary for the development of the disease.

Section 2
-
11 -
Sheep and goats have been shown to be susceptible to the development of BSE following
experimental exposure (i.c. and oral) (Foster et al., 1993, Foster et al., 1996, Bruce et al., 1994).
Different PrP genotypes have different incubation periods (Foster et al., 2001) following BSE
exposure.  Currently, there is no evidence that sheep and goats can develop the disease after
exposure to feed supplemented with contaminated animal protein.
Humans
In humans, polymorphisms in the PrP gene influence susceptibility to sporadic, inherited,
or infectious forms of prion diseases.  There are two common forms of PrP in humans with either
methionine (M) or valine  (V) at residue 129.  The population is comprised of homozygous M,
heterozygous M-V, and homozygous V. In Caucasians, 51% of the population are heterozygous
while 38% are methionine homozygous; the least common genotype is valine homozygous
(11%).  Variability of spontaneous CJD seems to be associated with physicochemical properties
of PrP
sc
in conjunction with the PRNP (human prion protein gene) codon 129 genotype (Parchi et
al., 1999).  In Kuru patients, homozygosity at residue 129 (particularly for methionine) was
associated with an earlier age at onset and a shorter duration of illness than was heterozygosity at
residue 129, a finding that probably reflects different disease incubation periods (Cervenakova et
al., 1998).
Homozygosity at residue 129 appears to increase susceptibility to TSE disease in
humans.  Cases of sporadic CJD are usually homozygous at residue 129 (Palmer et al., 1991).
Individuals with CJD caused by exposure to contaminated human pituitary hormone have an
elevated prevalence of homozygosity at residue 129 for valine (Collinge et al., 1991).  In familial
TSEs, polymorphism at codon 129 appears to influence the age of onset and the duration of the
disease (Dlouhy et al., 1992).  To date, all vCJD patients have been methionine homozygous (M-
M) at residue 129 (Will et al., 2000, Ironside et al., 2000).
Bovines
Investigators have identified polymorphisms in the PrP gene in British cattle, Belgian
cattle, and US cattle (for review refer to (SSC, 2000b)).  There are two major polymorphisms in
the region of the PrP gene:  1) the HindII restriction site, and 2) differences in the number of
copies (5 or 6) of an octapeptide repeat sequence (Goldmann et al., 1991, Hunter et al., 1994).

Section 2
-
12 -
Hunter et al. (1992) showed that there were no differences among breeds in the age of
onset of BSE.  Nor did the number of PrP octapeptide copies influence age of onset.  The absence
of an association between PrP polymorphisms and BSE onset age may indicate that BSE
incidence is associated with an “undiscovered” polymorphism of the PrP gene.  It could also
mean that there are other mutations that influence gene expression and potentially disease onset.
Alternatively, there may be only one predominant form of cattle PrP, and if this predominant
form were the allele that conferred susceptibility, most cattle would be genetically susceptible.  In
this case, the dose and route of exposure (assuming there is only one strain of BSE) determine
whether disease results.
Findings from the pathogenesis and the attack rate experiments (Wells et al., 1998, Wells
et al., 1999), in which animals were exposed to high levels of infectivity (1 to 100 times greater
than most cattle would have received naturally), indicate that most of the cattle challenged either
orally or parenterally succumbed to disease.  These results suggest that differences in
susceptibility between animals may not exist, or may not be important.  Alternatively, the
exposures may have been so high that they overwhelmed any differences in susceptibility.
Overall, it appears that if animals are exposed to high doses of the BSE agent early in life, they
will be very likely to develop disease.
Cattle have been shown to be partially susceptible to naturally induced scrapie but only
following intracerebral injection of infectious material (Gibbs et al., 1990, Clark et al., 1995,
Cutlip et al., 1994, Cutlip et al., 1997, Cutlip et al., 2001).  Studies done in the U.S. showed that
cattle orally exposed to North American scrapie remain normal for eight years following
exposure (Cutlip et al., 2001).  Research on cattle orally exposed to UK scrapie is ongoing (Linda
Detwiler, personal communication).  Currently, there are no available data indicating how
genetics might influence bovine susceptibility to scrapie.
Cervids
In a study of Rocky Mountain Elk, O’Rourke et al. (O'Rourke et al., 1999) found that
animals with CWD had an elevated prevalence of homzygosity for methionine at codon 132 of
the PrP gene.  This finding applied to both farmed and free-range animals.

Section 2
-
13 -
2.2
The Origin of the BSE Epidemic in the UK
In 1986, a bovine spongiform encephalopathy was first confirmed in the United Kingdom
as the result of routine animal disease surveillance.  This section focuses on theories advanced to
explain the origins of the subsequent epidemic.  Since the beginning of the epidemic, over


[Federal Register Volume 76, Number 153 (Tuesday, August 9, 2011)]
[Notices]
[Page 48845]
[FR Doc No: 2011-20063]

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registration, using the eComment system at http://www.ferc.gov/docs-filing/ecomment.asp. You must include your name and contact information
at the end of your comments. For assistance, please contact FERC Online
Support at<EMAIL_ADDRESS>call toll-free at (866) 208-
3676; or, for TTY, contact<PHONE_NUMBER>. Although the Commission
strongly encourages electronic filing, documents may also be paper-
filed. To paper-file, mail an original and seven copies to: Kimberly D.
Bose, Secretary, Federal Energy Regulatory Commission, 888 First
Street, NE., Washington, DC 20426.
    More information about this project, including a copy of the
application, can be viewed or printed on the ``eLibrary'' link of the
Commission's Web site at http://www.ferc.gov/docs-filing/elibrary.asp.
Enter the docket number (P-12862-002) in the docket number field to
access the document. For assistance, contact FERC Online Support.

    Dated: August 2, 2011.
Kimberly D. Bose,
Secretary.
[FR Doc. 2011-20063 Filed 8-8-11; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 81, Number 5 (Friday, January 8, 2016)]
[Notices]
[Pages 938-940]
[FR Doc No: 2016-111]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-0001]

Gastroenterology and Urology Devices Panel of the Medical Devices
Advisory Committee; Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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    This notice announces a forthcoming meeting of a public advisory
committee of the Food and Drug Administration (FDA). The meeting will
be open to the public.
    Name of Committee: Gastroenterology and Urology Devices Panel of
the Medical Devices Advisory Committee.
    General Function of the Committee: To provide advice and
recommendations to the Agency on FDA's regulatory issues.
    Date and Time: The meeting will be held on February 25, 2016, from
8 a.m. to 6 p.m. and February 26, 2016, from 8 a.m. to 1 p.m.
    Location: Hilton Washington DC North/Gaithersburg, Salons A, B, and
C, 620 Perry Pkwy., Gaithersburg, MD 20877. The hotel's telephone
number is<PHONE_NUMBER>.

    Contact Person: Patricio G. Garcia, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1611, Silver Spring, MD 20993-0002,
<EMAIL_ADDRESS>301-796-6875, or FDA Advisory Committee
Information Line, 1-800-741-8138<PHONE_NUMBER> in the Washington, DC
area). A notice in the Federal Register about last minute modifications
that impact a previously announced advisory committee meeting cannot
always be published quickly enough to provide timely notice. Therefore,
you should always check the Agency's Web site at http://www.fda.gov/AdvisoryCommittees/default.htm and scroll down to the appropriate
advisory committee meeting link, or call the advisory committee
information line to learn about possible modifications before coming to
the meeting.
    Agenda: On February 25, 2016, the committee will discuss, make
recommendations, and vote on information regarding the premarket
approval application (PMA) for ``TOPAS Treatment for Fecal
Incontinence,'' by ASTORA Women's Health, LLC. The ``TOPAS Treatment
for Fecal Incontinence'' device is a sling device (mesh) to be
implanted around the puborectalis muscle (a muscle that contributes
towards the maintenance of fecal continence). The proposed Indication
for Use (IFU) for the ``TOPAS Treatment for Fecal Incontinence''
device, as stated in the PMA, is as follows:
    The ``TOPAS Treatment for Fecal Incontinence'' is intended to treat
women with fecal incontinence (also referred to as accidental bowel
leakage) who have failed more conservative therapies.
    On February 26, 2016, during session I, the committee will discuss
and make recommendations regarding the reclassification of
urogynecologic surgical mesh instrumentation from class I to class II.
The applicable product codes are those related to urogynecologic
surgical mesh as follows:
     OTN and the associated device classification name, ``mesh,
surgical, synthetic, urogynecologic, for stress urinary incontinence,
female, multi-incision;''
     PAG and the associated device classification name, ``mesh,
surgical, non-synthetic, urogynecologic, for stress urinary
incontinence, female, multi-incision;''
     PAH and the associated device classification name, ``mesh,
surgical, synthetic, urogynecologic, for stress urinary incontinence,
female, single-incision mini-sling;''
     OTO and the associated device classification name, ``mesh,
surgical, synthetic, urogynecologic, for apical vaginal and uterine
prolapse, transabdominally placed;''
     PAJ and the associated device classification name, ``mesh,
surgical, non-synthetic, urogynecologic, for apical vaginal and uterine
prolapse, transabdominally placed;''
     OTP and the associated device classification name, ``mesh,
surgical, synthetic, urogynecologic, for pelvic organ prolapse,
transvaginally placed'' and
     PAI and the associated device classification name, ``mesh,
surgical, non-synthetic, urogynecologic, for pelvic organ prolapse,
transvaginally placed.''
    Some examples of the means by which these devices perform these
functions and their respective IFU/Intended Use (IU) statements are:
     Urogynecologic surgical mesh instrumentation is used:
    [cir] IFU/IU: To aid in insertion, placement, fixation, or
anchoring of surgical mesh for procedures including transvaginal pelvic
organ prolapse repair, sacrocolpopexy (transabdominal pelvic organ
prolapse repair), treatment of female stress urinary incontinence.
Examples of such surgical instrumentation include needle passers and
trocars, needle guides, fixation tools, and tissue anchors.
    The committee, during session II, will discuss and make
recommendations regarding the classification of the product code
``LKX'' and the associated device classification name, ``Device,
Thermal, Hemorrhoids.'' The product code LKX represents a category of
devices intended to apply controlled cooling and conductive heating to
hemorrhoids. These devices are considered preamendments devices since
they were in commercial distribution prior to May 28, 1976, when the
Medical Devices Amendments became effective. Some examples of the means
by which these devices perform these functions and their respective
IFU/IU statements are:
     Uses an aluminum probe that contains a temperature
sensitive element to regulate temperature within 2 degrees (between 37
and 46 degrees centigrade).
    [cir] IFU/IU: The apparatus is intended to apply controlled,
conductive heating to hemorrhoids.
     Uses a heat applicator inserted into the rectum,
applicator contains a battery operated heater, and a sensor which
provides temperature control/feedback.
    [cir] IFU/IU: Intended to provide temporary relief of the symptoms
of hemorrhoids through the application of mild heating.
     Uses speculum-like plastic container containing liquid to
cool hemorrhoidal veins.
    [cir] IFU/IU: Treatment of external hemorrhoids by applying cold
therapy (cryotherapy) directly to swollen hemorrhoidal veins.
    The committee, during session III, will discuss and make
recommendations regarding the classification of the product code
``LRL'' and the associated device classification name, ``Cushion,
Hemorrhoid.'' The product code LRL represents a category of devices
intended to temporarily relieve pain and pressure caused by
hemorrhoids. These devices are considered preamendments devices since
they were in commercial distribution prior to May 28, 1976, when the
Medical Devices Amendments became effective. Some examples of the means
by which these devices perform these functions and their respective
IFU/IU statements are:
     Uses an injection molded polypropylene copolymer plastic
seat attached to a toilet seat (the product is adjustable and is
available in round and elongated versions).
    [cir] IFU/IU: For the temporary relief from the pain and pressure
of hemorrhoids. The device is for external use only.
     Uses a cushion with an inflatable vinyl exterior and a
foam center. An air chamber, when filled, prevents the cushion from
compressing the foam. A urethane foam center adds comfort.
    [cir] IFU/IU: Intended for the home convalescent patient with
perineal discomfort.
     Uses a cushion that contains two internal molded
structures that conform to the patient's shape. Exerts ``slight''
pressure on hemorrhoid. IFU/IU not required at the time of clearance.
    The committee, during session IV, will discuss and make
recommendations regarding the classification of the product code
``LKN'' and the associated device classification name, ``Separator,
automated, blood cell and plasma, therapeutic.'' The product code LKN
represents a category of centrifuge-type devices intended to separate
blood components and perform therapeutic plasma exchange for the
management of serious medical conditions in adults and children. These
devices are considered preamendments devices since they were in
commercial distribution prior to May 28, 1976, when the Medical Devices
Amendments

became effective. Some examples of the means by which these devices
perform these functions and their respective IFU/IU statements are:
     Utilizes a continuous flow centrifuge (max speed 3000
revolutions per minute) to separate source blood from a subject into
blood components.
    [cir] IFU/IU: May be used to perform therapeutic plasma exchange.
    [cir] IFU/IU: May be used to perform Red Blood Cell Exchange
procedures for the transfusion management of Sickle Cell Disease in
adults and children.
     Uses continuous flow access to a rotating centrifuge to
separate blood components.
    [cir] IFU/IU: May be used to harvest cellular components from the
blood of certain patients where the attending physician feels the
removal of such component may benefit the patient.
    [cir] IFU/IU: May be used to remove plasma components and/or fluid
selected by the attending physicians.
    FDA intends to make background material available to the public no
later than 2 business days before the meeting. If FDA is unable to post
the background material on its Web site prior to the meeting, the
background material will be made publicly available at the location of
the advisory committee meeting, and the background material will be
posted on FDA's Web site after the meeting. Background material is
available at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm
and then by scrolling down to the appropriate advisory committee
meeting link.
    Procedure: Interested persons may present data, information, or
views, orally or in writing, on issues pending before the committee.
Written submissions may be made to the contact person on or before
February 17, 2016. Oral presentations from the public will be scheduled
on February 25, 2016, between approximately 1 p.m. and 2 p.m. and on
February 26, 2016, between approximately 8:30 a.m. and 9:30 a.m. Those
individuals interested in making formal oral presentations should
notify the contact person and submit a brief statement of the general
nature of the evidence or arguments they wish to present, the names and
addresses of proposed participants, and an indication of the
approximate time requested to make their presentation on or before
February 9, 2016. Time allotted for each presentation may be limited.
If the number of registrants requesting to speak is greater than can be
reasonably accommodated during the scheduled open public hearing
session, FDA may conduct a lottery to determine the speakers for the
scheduled open public hearing session. The contact person will notify
interested persons regarding their request to speak by February 10,
2016.
    Persons attending FDA's advisory committee meetings are advised
that the Agency is not responsible for providing access to electrical
outlets.
    FDA welcomes the attendance of the public at its advisory committee
meetings and will make every effort to accommodate persons with
disabilities. If you require accommodations due to a disability, please
contact AnnMarie Williams at<EMAIL_ADDRESS>301-796-
5966, at least 7 days in advance of the meeting.
    FDA is committed to the orderly conduct of its advisory committee
meetings. Please visit our Web site at http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures
on public conduct during advisory committee meetings.
    Notice of this meeting is given under the Federal Advisory
Committee Act (5 U.S.C. app. 2).

    Dated: January 4, 2016.
Jill Hartzler Warner,
Associate Commissioner for Special Medical Programs.
[FR Doc. 2016-111 Filed 1-7-16; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 85, Number 212 (Monday, November 2, 2020)]
[Notices]
[Pages 69380-69381]
[FR Doc No: 2020-24188]

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DEPARTMENT OF TRANSPORTATION

Federal Motor Carrier Safety Administration

[Docket No. FMCSA-2014-0106; FMCSA-2016-0002; FMCSA-2017-0061]

Qualification of Drivers; Exemption Applications; Hearing

AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT.

ACTION: Notice of final disposition.

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SUMMARY: FMCSA announces its decision to renew exemptions for eight
individuals from the hearing requirement in the Federal Motor Carrier
Safety Regulations (FMCSRs) for interstate commercial motor vehicle
(CMV) drivers. The exemptions enable these hard of hearing and deaf
individuals to continue to operate CMVs in interstate commerce.

DATES: The exemptions were applicable on September 6, 2020. The
exemptions expire on September 6, 2022.

FOR FURTHER INFORMATION CONTACT: Ms. Christine A. Hydock, Chief,
Medical Programs Division,<PHONE_NUMBER><EMAIL_ADDRESS>FMCSA,
Department of Transportation, 1200 New Jersey Avenue SE, Room W64-224,
Washington, DC 20590-0001. Office hours are from 8:30 a.m. to 5 p.m.,
ET, Monday through Friday, except Federal holidays. If you have
questions regarding viewing or submitting material to the docket,
contact Dockets Operations,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Public Participation

A. Viewing Documents and Comments

    To view comments, as well as any documents mentioned in this notice
as being available in the docket, go to http://www.regulations.gov/docket?D=FMCSA-2014-0106, http://www.regulations.gov/docket?D=FMCSA-2016-0002, or http://www.regulations.gov/docket?D=FMCSA-2017-0061 and
choose the document to review. If you do not have access to the
internet, you may view the docket online by visiting Dockets Operations
in Room W12-140 on the ground floor of the DOT West Building, 1200 New

Jersey Avenue SE, Washington, DC 20590, between 9 a.m. and 5 p.m., ET,
Monday through Friday, except Federal holidays. To be sure someone is
there to help you, please call<PHONE_NUMBER> or<PHONE_NUMBER> before
visiting Dockets Operations.

B. Privacy Act

    In accordance with 5 U.S.C. 553(c), DOT solicits comments from the
public to better inform its rulemaking process. DOT posts these
comments, without edit, including any personal information the
commenter provides, to www.regulations.gov, as described in the system
of records notice (DOT/ALL-14 FDMS), which can be reviewed at
www.transportation.gov/privacy.

II. Background

    On September 2, 2020, FMCSA published a notice announcing its
decision to renew exemptions for eight individuals from the hearing
standard in 49 CFR 391.41(b)(11) to operate a CMV in interstate
commerce and requested comments from the public (85 FR 54625). The
public comment period ended on October 2, 2020, and no comments were
received.
    FMCSA has evaluated the eligibility of these applicants and
determined that renewing these exemptions would achieve a level of
safety equivalent to, or greater than, the level that would be achieved
by complying with Sec.  391.41(b)(11).
    The physical qualification standard for drivers regarding hearing
found in Sec.  391.41(b)(11) states that a person is physically
qualified to drive a CMV if that person first perceives a forced
whispered voice in the better ear at not less than 5 feet with or
without the use of a hearing aid or, if tested by use of an audiometric
device, does not have an average hearing loss in the better ear greater
than 40 decibels at 500 Hz, 1,000 Hz, and 2,000 Hz with or without a
hearing aid when the audiometric device is calibrated to American
National Standard (formerly ASA Standard) Z24.5--1951.
    This standard was adopted in 1970 and was revised in 1971 to allow
drivers to be qualified under this standard while wearing a hearing
aid, 35 FR 6458, 6463 (April 22, 1970) and 36 FR 12857 (July 3, 1971).

III. Discussion of Comments

    FMCSA received no comments in this proceeding.

IV. Conclusion

    Based upon its evaluation of the eight renewal exemption
applications, FMCSA announces its decision to exempt the following
drivers from the hearing requirement in Sec.  391.41(b)(11).
    As of September 6, 2020, and in accordance with 49 U.S.C. 31136(e)
and 31315(b), the following eight individuals have satisfied the
renewal conditions for obtaining an exemption from the hearing
requirement in the FMCSRs for interstate CMV drivers (85 FR 54625):

Weston Arthurs (CA)
Mathias Conway (MI)
Charles DePriest (TX)
Agustin Hernandez (TX)
Robert Hilber (TX)
Richard Hoots (AR)
D'Nielle Smith (OH)
Michael Sweet (GA)

    The drivers were included in docket number FMCSA-2014-0106, FMCSA-
2016-0002, or FMCSA-2017-0061. Their exemptions were applicable as of
September 6, 2020, and will expire on September 6, 2022.
    In accordance with 49 U.S.C. 31315(b), each exemption will be valid
for 2 years from the effective date unless revoked earlier by FMCSA.
The exemption will be revoked if the following occurs: (1) The person
fails to comply with the terms and conditions of the exemption; (2) the
exemption has resulted in a lower level of safety than was maintained
prior to being granted; or (3) continuation of the exemption would not
be consistent with the goals and objectives of 49 U.S.C. 31136(e) and
31315(b).

Larry W. Minor,
Associate Administrator for Policy.
[FR Doc. 2020-24188 Filed 10-30-20; 8:45 am]
BILLING CODE 4910-EX-P