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The ethical justification for the use of animals
in biomedical research
ARTICLE in ARCHIVES OF BIOLOGICAL SCIENCES · JANUARY 2010
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DOI:10.2298/ABS1003781K
THE ETHICAL JUSTIFICATION FOR THE USE OF ANIMALS IN BIOMEDICAL RESEARCH
N. G. KOSTOMITSOPOULOS1 and S. F. ĐURAŠEVIĆ2
Center for Experimental Surgery, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000 Belgrade, Republic of Serbia
1
2
Abstract - Despite all the benefits, the use of animals in biomedical research is still a subject of debate with respect to its
true value. The sensitivity of the community and the interest of scientists who work in the field of laboratory animal
science and welfare have clearly demonstrated that the use of animals in biomedical research must be conducted under
specific scientific, legal and ethical rules. The ethical justification of a research project starts from its initial designing
phase until its completion and the review of the obtained results. Justification of the necessity of the project and the
need to use animals in the interests of human or animal health, the importance of conducting a pilot study and a
systematic review of previously published animal research on the topic, and the availability of the proper facilities,
equipment and personnel are the main issues of concern in the ethical review of a research project. The ethical
justification of the proposed project by the scientists themselves involves team-work, and should be a sustainable rather
than a one-off procedure. This justification reflects the interest and the responsibility of scientists to reduce the number
of animals, refine the procedures, and possibly replace animals in their research projects. The end-results of the ethical
review process will be the creation of a trust relationship between scientists and society.
Keywords: Laboratory animals, ethics, refinement, reduction, replacement, animal experimentation
UDC 17:59.08:001.8
INTRODUCTION
The use of animals in biomedical research has always
played an important role in the acquisition of
scientific knowledge for understanding basic
biological processes and for improving the quality of
life of humans and animals. Recently, the
development and use of genetically modified animals
have also given scientists the opportunity to better
study the role of specific genes, and this has created
new perspectives in combating and treating diseases
such as gene therapy. Despite all the benefits, the use
of animals in biomedical research continues to be a
subject of debate with respect to its true value.
Opponents on the use of animals in any kind of
research believe that animal experimentation should
be abolished immediately (Festing and Wilkinson,
2007). On the other hand, there are legal
requirements that oblige scientists who conduct
animal-based research to ensure that their
experiments are conducted humanely in order to
satisfy societal concerns and to ensure the quality of
their experimental results (European Council, 1986).
Nowadays,
animal
experimentation
is
considered an ethical issue (Nuffield Council on
Bioethics, 2005; Rollin, 2007). A variety of different
ethical review processes that are based mainly on
different legal systems and cultural backgrounds
have been established around the world. The aim of
these ethical reviews is to ensure that the 3R's
concept of Russell and Burch for the replacement of
animals to be used in the research project, reducing
the number of animals required for the research
project, and refinement of the experimental
procedures, are respected (Russell and Burch,
1959). Although there are no legal requirements in
the existing European Union (EU) legislation,
compulsory ethical review of all scientific uses of
animals exists in sixteen of the twenty EU countries
which are members of the Federation of European
Laboratory Animal Science Associations (FELASA)
781
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N. G. KOSTOMITSOPOULOS ET AL.
(Smith et al., 2007). This ethical review is done by
institutional, local, or national committees.
Furthermore, it is within the scope of the revised
EU Directive 86/609 to define and harmonize the
ethical review process within the member states of
the EU (European Commission, 2008). The
application guidelines of the Seventh Framework
Program of the EU require the ethical
documentation of all projects that propose the use
of animals. This requirement clearly demonstrates
that the EU is very concerned about the ethical use
of animals in EU-funded scientific projects. From
this perspective, scientists in the EU have a moral
obligation to ethically justify the use of animals in
any animal-based research project.
ETHICAL JUSTIFICATION
For many years, scientists justified the use of
animals in their experiments solely by referring to
their scientific value in human health and welfare.
Aside from a purely anthropocentric perspective,
ethical concerns about the compromised animal
welfare in animal experimentation cannot be
tempered by human benefits alone (Olsson et al.,
2007). It is equally important that the benefits of the
experiment are achieved with minimal negative
consequences to the animals.
No matter which process of ethical review is
applied, it is crucial that scientists realize the
importance of ethics in their animal-based research.
Scientists themselves should be aware of the need to
conduct an ethical justification of their projects.
Moreover, they should conduct ethical justification
of their project from its initial design until its
completion and review of the experimental results.
It is also the responsibility of scientists to acquire
knowledge about the locally existing laboratory
animal welfare legislation and to conform to the
letter and spirit of these laws.
The main objective of the ethical justification is
to ensure that the project is scientifically and
ethically justified as required by law. Moreover, the
process should ensure that the decision to use
animals for research was made after earnest
consideration of its specific animal welfare issues,
and that the project is designed in such a manner
that it will be conducted humanely and be
environmentally-friendly. The ethical justification
of a research project by scientists themselves
involves teamwork, and should be sustainable
rather than being a one-off procedure. In order for
the process to be effective, the ethical justification of
a project by a research team should be supportive
and result from an open discussion and exchange of
opinions among its members. For this purpose, the
active collaboration between scientists with
different background knowledge within the
research group is necessary. A biostatistician can
assist the researchers in obtaining valid statistical
results from the minimum possible number of
animals. A laboratory animal veterinarian can
contribute to the refinement of the experimental
techniques by suggesting the most appropriate
anesthetic and analgesic protocol for the
experimental procedure, the determination of a
humane experimental endpoint, and the method of
euthanasia. It is very important that a layperson be
involved in discussions about the aims of the
project. This person represents the community, and
can convey societal concerns to the scientists about
the proposed project. Ethical justification should
ensure also that the humane care and use of the
animals will take place from the beginning to the
end of the animal experiment.
Justification of the necessity of the project
The primary concern of the research team is to
justify the necessity of the project itself, the
likelihood of its success, and, of course, the
scientific significance of the project for the benefit
of human or animal health. To this end, researchers
should state clearly: (a) the objectives of the
research project and/or the hypotheses to be tested,
(b) the reason for choosing a particular animal
model, (c) the animal species and strains to be used,
as well as the supply sources, (d) the details of each
separate experiment that will be conducted in the
research project, (e) the study design and the
THE ETHICAL JUSTIFICATION FOR THE USE OF ANIMALS IN BIOMEDICAL RESEARCH
number of animals to be used, and (f) the statistical
methods that will used to analyze the experimental
results.
Justification of the need of the research project,
clarification of its goals, and its predicted scientific
benefits are based mainly on the amount of scientific
knowledge of the research team. This information
should be presented in the application by providing
the relevant background information and bibliography and highlighting the unresolved problems.
This avoids unnecessary duplication of research,
although duplication may be required in pilot studies
that involve a novel method. The research team
should also clearly define their expectations of the
research project, and in what way this new information will increase the existing scientific knowledge
and/or benefit the health or welfare of humans or
animals. The social impact of the project should be
stated also. Finally, the scientific purpose of the research project should be of sufficient substance in
order to justify the use of animals.
Justification of the use of animals
Prior to any animal use, a cost-benefit analysis should
be done in order to determine whether the obtained
benefits of the animal-based research will outweigh
the cost to the animal(s). The term “cost” defines the
expected harm, pain and distress that is likely to be
experienced by the animals during the conduct of the
research project. The term “benefit” defines the
potential benefits of research that might be realized for
humans, other animal species, or the environment.
The use of animals in a research project is only
acceptable when its expected benefits will outweigh
the physiological and psychological harm that will be
caused to the animals. When preparing a research
protocol, special concern should be given to the
minimization of pain, distress and discomfort, and the
maximization of possible benefits.
For many years, the 3R's concept of Russell and
Burch on the reduction, refinement and replacement of animals has become an integral component
of the design and the realization phases of an
animal experiment (Russell and Burch, 1959;
783
Guhad, 2005). Replacement refers to methods
which avoid or replace the use of animals in a
research project where animals would otherwise
have been used. This includes both absolute
replacement of animals with systems or methods,
such as in vitro methods and computer programs,
and relative replacement such as replacing sentient
animals, such as vertebrates, with less sentient
animals such as some invertebrates that, according
to current scientific evidence, have a significantly
lower potential for pain perception (Wakefield et
al., 2002). The research team should provide all the
necessary documentation of the replacement
methods that were considered during their
planning discussions of the research project. In
some cases, the replacement methods could
contribute to the reduction of the number of
animals that will be used in the research project. In
vitro or in silica techniques could be used, for
example, to monitor the influence of nanomaterials
on the cardiovascular system and circulating blood.
Reduction refers to any strategy that will result in
sufficient data to answer the research question by
using the smallest number of animals in order to
obtain valid experimental results, or by maximizing
the information obtained per animal. In this way,
subsequent use of additional animals and
compromising animal welfare can be avoided or
potentially limited. The number of animals to be
used in a research project can be minimized by
several means. Scientists should know what has been
done previously by other scientific teams in the
chosen area of research and use this information to
estimate the number of animals needed in order to
produce reliable results. The number of animals to
be used in the research project can be reduced also
by good experimental design and careful observation
so that several variables can to be analyzed
simultaneously (McConway, 1992; Chiarotti and
Puopolo, 2000; Nevalainen, 2004). The research team
should also keep in mind that using too many
animals can lead to the unnecessary use of animals,
and using too few animals may require repetition of
the entire experiment because the results may be
unreliable after analysis of the data. In both
784
N. G. KOSTOMITSOPOULOS ET AL.
instances, there is wastage of animals and other
resources (Festing and Altman, 2002; Festing, 2006).
animals which should be performed by trained
personnel only (Morton and Griffiths, 1985).
Refinement refers to any modification of animal
husbandry or experimental procedure that will
result in the minimization of pain and distress and
in the enhancement of the welfare of an
experimental animal during its entire life.
Refinement is a process that begins with a critical
evaluation of the experimental intervention. It also
encompasses an assessment of animal welfare, the
recognition of poor or suboptimal welfare and
identification of the causes, the selection of welfare
improvement strategies, and the implementation of
one, some, or all of these strategies. Any changes
then have to be evaluated for their efficacy. In doing
so, a refinement loop can be created because the
process begins again (Lloyd et al., 2008).
The ethical justification should include an
assessment of the estimated pain, and the severity of
the procedure should be classified (Smith et al.,
2008). A retrospective analysis is recommended
also in order to compare the intensity of actual and
predicted pain in the experimental animals
(Jennings et al., 2005).
Housing animals under minimal conditions by
providing, for example, only food, water and bedding,
are likely to cause some distress to the animal even
before any experimental procedures have been
initiated. Refinement of housing conditions by
environmental enrichment (social or physical) could
minimize the discomfort of the animals (Baumans et
al., 2006; Kostomitsopoulos et al., 2007). If housing
animals under minimal conditions is necessary, it
should be ethically justified.
Special concern should be also given to
procedures that minimize pain, suffering and
distress. For any project that might involve pain,
suffering or distress, the research team should
assess thoroughly whether the information that is to
be gained can be justified, and explore whether
non-animal alternatives can be used. Any
procedure that is likely to cause pain should only be
performed under adequate local or general
anesthesia and with appropriate analgesia, unless
anesthesia and/or analgesia compromise the
experimental aims (Bateson, 1991). /If it is decided
that either anesthesia or analgesia are not to be used
to alleviate pain, this should be ethically justified.
Special concern should be given also to the
recognition of an early humane experimental
endpoint, and the method of euthanasia of the
Special justification should be provided when
creating and using genetically modified animals.
Special attention should be shown to these animals
whose health and/or welfare may be compromised
because of gene modification(s) (van der Meer et
al., 2001; Wells et al., 2006).
The pilot study
A pilot or feasibility study is a small experiment that
is designed to test the logistics of the proposed
research project, and to gather this information
prior to a larger study. Therefore, it is conducted in
order to improve the quality and efficiency of the
project. A pilot study can reveal deficiencies in the
design of a proposed experiment or procedure
which can then be addressed before time and
resources are expended in the large-scale study. For
an animal-based experiment, a pilot study can
provide useful information on the estimated
number of animals that are needed for the study, as
well as information on the severity of proposed
procedures or treatment. When conducting a pilot
study, the research team will have the opportunity
to further refine the experimental procedure(s) by
using different anesthetic or analgesic protocols or
advancing the humane endpoint to an earlier time
point. Lastly, pilot studies should use a small
number of animals, and should always be approved
by an ethical review panel beforehand (National
Centre for the Replacement; Morton, 2008).
Systematic review of animal research
The systematic review is a synthesis of all available
research literature by addressing a specific research
THE ETHICAL JUSTIFICATION FOR THE USE OF ANIMALS IN BIOMEDICAL RESEARCH
question using a systematic approach. Systematic
reviews involve: (a) a planned, rigorous, clearly
defined and explicitly documented methodology, (b) a
specific search of bibliographic databases to identify all
relevant studies, (c) appraising and selecting studies
for the review using defined criteria, (d) analyzing the
experimental methods of all the included studies to
assess the quality of the study design and conduct, and
(e) assessing the results of the included studies
(National Centre for the Replacement). Part of the
systematic review is meta-analysis which is a statistical
technique for combining the numerical results from
the independent studies that were reviewed in the
systematic review (Deeks et al., 2001). The metaanalysis result increases statistical precision. It
represents an overall and more reliable estimate of the
treatment effectiveness of healthcare interventions
than the results of an individual study alone.
Systematic review and meta-analysis have a
positive impact when considering the 3R's. A
systematic review could result in reducing the
number of the animals because duplicate animal
experiments would not be performed. Metaanalysis of the results of previously published
similar experiments will allow a more precise
estimation of the number of animals that need to be
used in the proposed research project. Systematic
reviews of comparative studies could be used to
provide evidence of the effectiveness of
refinements. They could also be used to provide
evidence of the effectiveness and validity of in vitro
studies, the use of invertebrates, or in silica data
with traditional animal models such as when used
for testing the efficacy of a particular drug
(National Centre for the Replacement).
Facilities, equipment and personnel
The research team should justify the availability of
the appropriate experimental facilities, equipment,
and personnel that are required to conduct the
animal experimentation. The housing conditions
and facilities for experimental animals must comply
with existing national or international legislative
requirements or guidelines that relate to animal
health and welfare (National Research Council,
785
1996; European Commission, 2007). Depending on
the animal species, researchers should consider not
only the minimum housing and management
requirements that are set out in legislation, but
should also refer to the most recently published
literature on these topics in order to consider
improvements to the housing and management of
their experimental animals. All the necessary
equipment for the realization of the animal
experiment should be available to ensure the quality
of the experiment.
It is imperative that the people who work with
experimental animals are fully trained in animal
care and understand the needs of the species they
are caring for, as well as the experimental
procedures that are to be used in the research
project. This includes the ability to observe and
assess when an animal may be in pain or distressed,
and the knowledge to then take the relevant
measures to effectively alleviate pain or distress as
quickly as possible. Animal carers should be fully
aware of the legislation that is relevant to the
housing and management of experimental animals,
and their use in a particular study. The researcher
should ensure that all personnel are responsible,
trustworthy and have the relevant experience to
perform their specific duties within the study.
Education and training guidelines are available
from numerous international organizations and
scientific associations, such as the Council of
Europe, the World Health Organization, and
FELASA (Council of Europe, 1993; Nevalainen
Convenor et al., 2002).
CONCLUSIONS
Despite the fact that many alternative methods for
replacing animals exist, the use of animals in
biomedical research is still unavoidable. The public
expects high standards of care and use to be applied
to research animals. Legal requirements oblige the
scientists who conduct animal-based research to
ensure that their experiments are conducted
humanely in order to satisfy societal concerns, and
to ensure the quality of their experimental results.
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N. G. KOSTOMITSOPOULOS ET AL.
These clearly define the moral obligation of the
research team to ethically justify the animal
experimentation to the ethical review panel and to
the community. The ethical justification of
laboratory animal research protocols reflects the
interest and the responsibility of scientists to reduce
the number of animals, refine the procedures and
possibly replace animals in their research projects.
This process will build a trust relationship between
scientists and society. It is also very important to
educate the next generation of scientists to think
about both ethics and science. As animal welfare
goes, there should be no doubt that ethics must go
hand-in-hand with good science in order to further
improve animal-based biomedical research.
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