Use of Most Animal Species Has Declined
Over the Decades
Data for the United States. Data for rats, mice, birds, and cold-blooded vertebrates are not tracked.
Source: United States Department of Agriculture (USDA) Annual Reports
Use of Most Animal Species Has Declined
Over the Decades
Data for the United States. Data for rats, mice, birds, and cold-blooded vertebrates are not tracked.
Source: United States Department of Agriculture (USDA) Annual Reports and National Institutes of
Health (NIH) website.
Use of Most Animal Species Has Declined
Over the Decades; the Exception is Mice
Data for the United Kingdom.
Source: United Kingdom Home Office Website.
The Fall of the Feline in Neurophysiological
Studies
¹
Although rodents have traditionally been the major species
utilized for many types of neuroscience research (e.g., behavioral
studies), felines were a major species used for neurophysiological
studies prior to the mid-1980s.
¹
Examples are studies of visual processing by the brain (Nobel
prize for Hubel and Wiesel in 1981) and processing of
somatosensory inputs by the spinal cord (Nobel prize for Eccles
in 1963).
¹
Cats were popular research animals for classical
neurophysiological studies because they:
¾
¾
¾
Could withstand the extensive surgeries required
Were large enough to accommodate bulky instrumentation
Were inexpensive models (obtained from pounds or animal shelters;
limited paperwork requirements)
The Fall of the Feline in Neurophysiological
Studies
¹
In the mid-1980s, new regulations
substantially increased the cost of
the feline model.
¹
Miniaturization of instrumentation
allowed rodents to serve as
replacements for felines in some
studies.
¹
Public opinion became negatively
biased against the use of
companion animals in research.
¹
Chronic recording techniques
allowed a single animal to be
studied over a prolonged time, such
that fewer animals were needed for
a study. The use of nonhuman
primates became economically
feasible.
¹
Nonhuman primates can be
trained for more elaborate tasks
than cats, allowing for
sophisticated studies of neural
function.
The Transgenic Mouse Revolution
¹
The first knockout mouse was created
by Mario R. Capecchi, Martin Evans and
Oliver Smithies in 1989, for which they
were awarded the Nobel Prize for
Medicine in 2007.
¹
The mouse is the only mammalian
species that has been readily amenable
to gene knockout (until recently).
¹
It is also now possible to insert human
genes into a mouse, and to overexpress
particular genes.
¹
Use of transgenic animals has allowed
neuroscientists to decipher the function
of particular genes, and to create
disease models.
Source: Website of the Nobel Prize in Physiology or
Medicine 2007.
The Transgenic Mouse Revolution
¹
Use of knockout animals has
provided a number of critical
advances in neuroscience
research:
¾
¾
¹
Knockout mouse models of
Alzheimer’s disease are
shedding light on treatment
options.
Knockout mouse models
have been critical in
understanding the neural
basis of learning and
memory.
Transgenic mice likely
account for ~ ⅔ or more of
the mice, and over half of the
mammals, used in biomedical
research.
# Procedures on Mice
in UK, 2009
Normal
Animal
Transgenic
Animal
Source: United Kingdom Home Office Website
Limitations of the Transgenic Mouse
¹
Some genetic diseases have different characteristics in mice
and humans:
¾
¾
Transgenic models of Parkinson’s disease often don’t exhibit
the same neural degeneration that humans do.
Although the mouse Huntington gene is 81% identical to the
human Huntington gene, knockout of the gene in mice leads to
death during embryogenesis (in contrast, the human disease
emerges in adulthood).
¹
Diseases that involve multiple genes have been difficult to
create in transgenic models.
¹
Compensation for the effects of gene manipulation can
occur, which can lead to false conclusions about the role of
particular genes.
Are Rodents Ideal Research Models?
PROs
CONs
¹
Rodents typically live < 2
years, which facilitates
aging studies
¹
Rapid aging can confound
repeated measures over time in
the same subject
¹
The small size of rodents
allows many animals to be
maintained in a limited
space
¹
The small size of rodents
provides constraints on the
manipulations and
measurements that are possible
¹
Rodents serve as excellent
models of some human
diseases
¹
Some human disease
conditions cannot be mimicked
in rodents
Research results need to be reproduced in multiple species to assure they are
shared between all mammals. Some findings in rodents might be unique for
rodents.
Some Studies are Better Done in
Carnivores
¹
Rodents and rabbits lack the ability to vomit, such that
carnivores remain the best model animals to study emesis and
conditions that elicit emesis (e.g., motion sickness).
¹
Rodents lack respiratory responses such as coughing and
sneezing; carnivores remain the best model for studying cough
suppressing drugs.
¹
Ferrets are susceptible to most strains of influenza that infect
humans, and are the best animal models for influenza
treatments.
¹
Feline immunodeficiency syndrome remains one of the best
analogs of human acquired immunodeficiency syndrome
(AIDS).
Universal Knockouts
¹
Zinc-Finger Nuclease technology has
allowed the creation of knockout rats.
¹
Theoretically, the technique should work for
inactivating genes in any species, including
humans.
¹
The balance of species used in biomedical
research may change as new transgenic
animals become available.
New Regulatory Challenges
¹
New regulatory challenges are on the
horizon in the United States and
Europe.
¹
Impacts of the new regulations are
increased recordkeeping
requirements, and increased cost of
conducting biomedical research.
¹
It is unclear whether the increased
costs and burdens will be paralleled
in improved animal welfare.
Conflicting Regulatory Challenges
¹
In addition to animal welfare regulations
(two laws in the United States, and two
sets of regulations), many additional rules
and standards are applicable to research
using animals.
¹
For example, transgenic animals fall
under the regulation of NIH’s Office of
Biotechnology Activities (OBA).
¹
The US Food and Drug Administration
(FDA) has also claimed oversight
authority for transgenic animals, but has
not yet exerted oversight action (except
for genetically engineered food species).
9 The promulgation of overlapping and
confusing regulations increases the
cost of biomedical research, thereby
limiting scientific progress.
9 There is little consideration for
balancing animal welfare and
regulatory burden.
9 It is rare to consider the
investigator’s perspective during
rulemaking.
9 Streamlined regulations are needed
that protect animals while facilitating
progress.