Introduction
Animal experimentation falls under two categories: Basic (investigation of basic biology and
human disease) and applied (drug research and development and toxicity and safety testing).
Regardless of its categorization, animal experimentation is intended to inform human biology
and health sciences and to promote the safety and efficacy of potential treatments. Although it is
widely accepted that medicine should be evidence based, animal experimentation as a means
of informing human health has generally not been held to this standard. It makes it surprising
that animal experimentation is typically viewed as the default and gold standard of preclinical
testing.
Problems of Successful Translation to Humans of Data from Animal Experimentation
Although the unreliability and limitations of animal experimentation have increasingly been
acknowledged, there remains a general confidence within much of the biomedical community
that they can overcome. Three major conditions undermine this confidence and explain why
animal experimentation, regardless of the disease category studied, fails to reliably inform
human health.
The influence of Laboratory Procedures and Environments on Experimental Results
Laboratory procedures and conditions exert influences on animal's physiology and behaviors
that are difficult to control and that can ultimately impact research outcomes. Captivity and the
common features of biomedical laboratories can prevent species-typical behavior, causing
distress and abnormal behaviors among animals. Among the types of laboratory-generated
distress is the phenomenon of contagious anxiety. Blood pressure and heart rates rise in
animals that see other animals being decapitated or restrained. Routine laboratory procedures,
in addition to the experimental procedure, cause significant and prolonged elevations in animal's
stress markers. These have a significant effect on test results. A variety of conditions in the
laboratory cause changes in neurochemistry, genetic expression, and nerve regeneration. In
order to control for potential confounders, some investigations have called for standardization of
laboratory settings and procedures. There are important influences of environmental conditions
and procedures specific to individual laboratories that can be difficult to eliminate.
The Discordance between Human Diseases and Animal Models of Diseases
The lack of sufficient congruence between animals models and human diseases is another
significant obstacle to translational reliability. Human diseases are typically artificially induced in
animals, but the enormous difficulty of reproducing anything approaching the complexity of
human diseases in animal models limits their usefulness. The translation of results from animal
model to the clinic may fail because disparities between the animal experimental model and the
human condition.
Accurately modeling strokes in animals has proven to be an exercise in futility. To
address the inability to replicate human stroke in animals, many assert the need to use more
standardized animal study design protocols. A set of guidelines, named STAIR, was
implemented by a stroke roundtable in 1999 to standardize protocols, limit the discrepancies,
and improve the applicability of animal strok experiments to humans. It is not difficult to surmise
why animal stroke experiments fail to successfully translate to humans even with new
Animal experimentation falls under two categories: Basic (investigation of basic biology and
human disease) and applied (drug research and development and toxicity and safety testing).
Regardless of its categorization, animal experimentation is intended to inform human biology
and health sciences and to promote the safety and efficacy of potential treatments. Although it is
widely accepted that medicine should be evidence based, animal experimentation as a means
of informing human health has generally not been held to this standard. It makes it surprising
that animal experimentation is typically viewed as the default and gold standard of preclinical
testing.
Problems of Successful Translation to Humans of Data from Animal Experimentation
Although the unreliability and limitations of animal experimentation have increasingly been
acknowledged, there remains a general confidence within much of the biomedical community
that they can overcome. Three major conditions undermine this confidence and explain why
animal experimentation, regardless of the disease category studied, fails to reliably inform
human health.
The influence of Laboratory Procedures and Environments on Experimental Results
Laboratory procedures and conditions exert influences on animal's physiology and behaviors
that are difficult to control and that can ultimately impact research outcomes. Captivity and the
common features of biomedical laboratories can prevent species-typical behavior, causing
distress and abnormal behaviors among animals. Among the types of laboratory-generated
distress is the phenomenon of contagious anxiety. Blood pressure and heart rates rise in
animals that see other animals being decapitated or restrained. Routine laboratory procedures,
in addition to the experimental procedure, cause significant and prolonged elevations in animal's
stress markers. These have a significant effect on test results. A variety of conditions in the
laboratory cause changes in neurochemistry, genetic expression, and nerve regeneration. In
order to control for potential confounders, some investigations have called for standardization of
laboratory settings and procedures. There are important influences of environmental conditions
and procedures specific to individual laboratories that can be difficult to eliminate.
The Discordance between Human Diseases and Animal Models of Diseases
The lack of sufficient congruence between animals models and human diseases is another
significant obstacle to translational reliability. Human diseases are typically artificially induced in
animals, but the enormous difficulty of reproducing anything approaching the complexity of
human diseases in animal models limits their usefulness. The translation of results from animal
model to the clinic may fail because disparities between the animal experimental model and the
human condition.
Accurately modeling strokes in animals has proven to be an exercise in futility. To
address the inability to replicate human stroke in animals, many assert the need to use more
standardized animal study design protocols. A set of guidelines, named STAIR, was
implemented by a stroke roundtable in 1999 to standardize protocols, limit the discrepancies,
and improve the applicability of animal strok experiments to humans. It is not difficult to surmise
why animal stroke experiments fail to successfully translate to humans even with new
