Animal people and animals benefit because of these

Animal research
has had a crucial role in many of the scientific and medical advances of the
past century and continues to support our understanding of various diseases.

Worldwide, people and animals benefit because of these medical advances, and
the subsequent development of new medicines and treatments. Without animal
research, much of this advancement would likely have been impossible (Festing and
Wilkinson 2007).

In clinical
testing laboratories, experimental animals are removed from their groups and
used as a tool regardless of their natural instincts and either the whole
animal or its organs and tissues are used for the experimental procedures. For
this purpose animals are euthanized or if the animals survive the clinical
testing they are euthanised at the end of the experiment (Rusche, 2003). The issue of the pain,
distress and death the animals experience in scientific experimentation has
been a debating issue for a long time (Doke and Dhawale, 2015), which
continues to generate public and political concern worldwide (Taylor et al.,
2008).

The advancement
of research and development in medical technology has led to an upsurge in the
number of animals used in research. The percentage of articles reporting the
use of animals has increased in the past 15 years. With the rising popularity
of genetic modification methods, it is reported that genetically-modified
animal use has more than doubled since 1997 (Ormandy et al., 2009).

Several
estimates of global laboratory animal use have been published. Unfortunately,
the accuracy of animal use estimates has been significantly impeded by considerable
variation in reporting standards internationally (Knight, 2011). Many countries
only record or publish live animal use, and exclude the substantial number of animals
killed prior to procedures for purposes such as the harvesting of organs or
other tissues. Some countries do not record or publish animal use statistics at
all. This is why the comprehensive figure of 115.3 million animals used
worldwide yearly for research calculated by Taylor et al. (2008) may still be an underestimate. The considerable
number of animals that are being used yearly is one of the reasons possible alternatives
need to be investigated.

Animal experimentation
is generally accepted in society on the basis that progress in medical and
biological research relies on the use of experimental animals (Festing et al., 2002) and because of the claimed
benefits animal experimentation provides for human beings. Based on the
presumption that laboratory animal models reasonably reflect human outcomes and
reactions, animal research is widespread in its use in the safety and efficacy
testing of drugs and other clinical interventions.

Animals are
also used in education, particularly for medical and veterinarian education.

Veterinarians may have the largest justification for using animals, as trainee veterinarians
must be able to provide treatment for real animal patients once qualified and
recognise the clinical signs of diseases, as well as perform a variety of
surgeries and procedures including euthanasia for injured or terminally ill
patients (Knight, 2011).

Despite the numerous
advantages animal research has provided and continues to provide, the call for non-animal
alternatives is ever-increasing. Certain groups of people take an extreme view
that we have no right to make use of animals for our advantage, for food,
clothing, pleasure, research, or anything else (Smyth, 1978). From a
philosophical perspective one may question why humans have made the assumption
that we are free to use animals however we wish. Could the simple answer be because
of utilitarian reasons: we believe that the cost of the animal lives is worth
it for the benefit of humans?

The general
consensus among the public, including many of those who have no objections to
using animals in other ways such as for food or clothing, is that it is wrong
to cause pain to animals. It is generally accepted that the assumption of the
right to use animals goes with the responsibility not to cause unnecessary pain
or distress. A significant motivation in the search for alternatives to animal
experimentation is ultimately to avoid causing pain to animals. If experiments could
possibly involve inflicting pain on animals then, ethically, there is not only
a need to consider alternatives, but if these are not feasible, to ask whether
the resulting information is worth the pain caused (Smyth, 1978).

In the European
Union it is a legal requirement that a scientist planning a research project
that could involve vertebrates (and some other species such as Octopus vulgaris) must consider whether
its objectives could be achieved using alternative methods. Although this legal
requirement may not exist in other countries, it is ethically and economically
desirable to consider other alternatives (Festing et al., 2002).

As a result of
the animals that are used for medical and veterinary education, adverse impacts
may be experienced by students. The use and disposal of healthy animals may
cause powerful emotional experiences and high degree of stress which have great
potential to affect the students’ learning adversely, and indeed their own
health (Knight, 2011).

The expense of
research involving animals can be a negative aspect, especially if claims that
animals are not as useful are true. Apart from the cost of the animals if
bought, the cost feeding and maintaining the animals themselves can mount. If
alternatives to animals in research could possibly be cheaper, this may be a
solution to economic issues of animal experimentation and should be
investigated (Smyth, 1978).

Animals
frequently fail to accurately mirror human responses with sufficient accuracy. Variances
between different species may exist in absorption, distribution, metabolism,
and elimination pathways or rates, resulting in differing toxico- or
pharmacokinetics. Differences may also occur in toxico- or pharmacodynamics,
and all of these factors may contribute to differences in the organ systems
affected, and in the nature and magnitude of those effects. Given this, there
may be a need for researching into alternatives that will give more accurate results
to correspond with a human response.

In addition,
stresses that can be experienced by the laboratory animals when they are being
handled and during routine laboratory procedures, especially the stressful
methods of dose administration during toxicity tests can have an effect on the
outcome. Such stresses have the potential to alter their physiological,
hormonal, and immune status in ways that may alter the progression of diseases
and distort responses to chemicals and test pharmaceuticals, thus rendering any
results of the experiment less accurate (Knight, 2011).

With all
experiments, whether it is required by law or not, it is ethically desirable
for some sort of cost/benefit analysis to be considered, where the cost is the
pain, suffering and distress or death inflicted upon the animals, and the
benefit is the probability that the project will be successful and provide
potential benefits to humans or animals (Festing et al., 2002).

The Three Rs
(Reduction, Replacement and Refinement) were first proposed by Russel and Burch
(1959). They have become widely accepted principles in the governance of humane
animal research (Ormandy et al., 2009). These
principles encourage researchers to consider reducing the number of animals
used in experiments to a minimum that is necessary, refine the experiment to
limit the pain and distress to which animals are exposed, and replace the use
of animals with non-animal alternatives wherever possible (Ferdowsian and Beck,
2011).

Activists
against the use of animals in experiments are increasingly gaining support of
the wider public, putting significant pressure on government officials to put
harsher restrictions on animal experimentation (Bennett and Ringach, 2016). Various
alternatives to the use of animals in research have been suggested which can
avoid the use of animals in such research (Balls, 2002). These
methods can provide a substitute for drug and chemical testing up to an extent
(Doke and Dhawale, 2015).

During
the past two decades the development and availability of non-harmful teaching
methods has risen significantly. These include computer simulations, high
quality videos, ethically sourced cadavers (acquired from animals that have
been euthanised for medical reasons), models, and surgical simulators. Ideally,
humane veterinary surgical
courses that make use of non-animal alternatives when possible are comprised of
several stages. Students could begin by learning basic manual skills, such as suturing
and instrument handling, then progress to using knot-tying boards, plastic
organs, and similar models (Knight, 2011).

No pain will be involved by avoiding the dissection of animals, and models will
reduce the number of animals used (Smyth, 1978). They may then move on to practice
surgery performed on ethically sourced cadavers. Finally, students will watch,
assist with, and then perform under close supervision surgery on real patients
that benefit from the surgery rather than healthy animals that would be later euthanized
(Knight, 2011).

In vitro cell and tissue cultures is an
important alternative for animal experiments. It involves the isolation of
cells or tissues taken from an organ (liver, kidney, brain, skin, etc.) of an
animal and kept outside of the body in a suitable growth medium for an extended
period. They provide an opportunity to study the cellular response in a closed
system, where the experimental conditions can be preserved. These models can
provide preliminary information for the results of in vivo experiments (Doke and Dhawale, 2015). Although this does
not eliminate animals entirely from the equation, it reduces the total number
of animals used. In vitro cell and tissue cultures are often used for
initial screenings of molecules or chemicals of drugs to review their toxicity
and efficacy (Steinhoff et al., 2000). In fact, the toxicity and
efficacy of almost all cosmetics, drugs and chemicals are tested for using
these kinds of experiments (Doke and Dhawale, 2015). If humans or human tissues
are used in vitro, this can have many advantages as this alternative may
generate faster, cheaper results that are more reliably predictive for human
outcomes, and may deliver greater insights into human biochemical processes (Knight,
2011).

Computers can be
utilised to assist scientists in understanding the various basic principles of
biology and may have the potential to replace animals in the future. Computer
generated simulations are able to predict the different biological and toxic
effects a chemical or potential drug candidate can have and from these primary
screenings, promising molecules go on to be used for in vivo experimentation
(Doke and Dhawale, 2015). All of the major
pharmaceutical and biotechnology companies in the world make use of computational
design tools. A noteworthy
software known as Computer Aided Drug Design (CADD) is a practical assistance
to drug designers and is a significant guide to drug synthesis
(Richards, 1994). CADD can be used to identify likely receptor binding sites of
a drug molecule, which avoids in vivo testing
of chemicals that have no biological activity (Vedani, 1991). Consequently,
the total number of animals used in preliminary drug testing experiments
decreases, achieving the objectives of the three Rs (Doke and Dhawale, 2015).

In comparison to conducting experiments using animals to identify receptor
binding sites, such computerised systems are rapid and inexpensive (Knight,
2011) and therefore desirable due to their economic benefits over animal
experimentation.

While these computer
generated simulations can give researchers ideas of possibilities of drug
design and predictions of the properties of these new drugs, it cannot test out
the subsequent drug produced. Practically, this must be done on animals, meaning
that this is not truly an alternative to animals. They also enable the
researchers to make more use of the data they get from animal experiments, and
it may facilitate the researchers to design better experiments which will lead
to better quality results ultimately reducing total animals used in
experimentation in the future (Smyth, 1978).

Microdosing is a relatively new
method of obtaining human metabolism data through which human
participants are administered a small dose of a test compound which allows researchers to study
the pharmacological effects without harming the participants. Microdosing allows safer human studies as well as
reducing the use of animals in preclinical toxicology. It will also permit
smarter candidate selection by taking investigational drugs into humans earlier
(Lappin and Garner, 2003).

Replacement
could also mean replacing ‘higher’ animals with ‘lower’ animals. Eggs, plants,
reptiles, amphibians, microorganisms and invertebrates are all examples that
have been used to replace warm-blooded animals in studies (Ranganatha and
Kuppast, 2012). However, the majority of animals used in laboratories are
higher vertebrates, such as mammals and birds. These higher animals are known
to possess the psychological and neuro-anatomical capacities necessary to feel
pain, fear, and distress, making it ethically undesirable to use them for
experimentation (Knight, 2011).

In many
countries animal use legislations often only regulate the use of live
vertebrates, so the use of minimally sentient animals from lower phylogenetic
orders or early developmental vertebral stages in experimentation is an
attractive option as its increases compliance to such legislations (Knight,
2011).

Lower
vertebrates are frequently used since they are closely genetically related to
higher vertebrates including mammals (Doke and Dhawale, 2015). An example of which is
zebra fish, which make ideal model organisms for the study of
vertebrate development. This is due to a quick generation time, and a couple are able to
produce up to 200 embryos every 7 days. Furthermore, the embryos and larvae are
small and robust, go through rapid external development and are transparent (Tavares
and Lopes, 2013).

Invertebrate
organisms have been used as models for research and teaching for hundreds of
years. However, invertebrates do not have an adaptive immune system and have an
undeveloped organ system which limits their use as models in human diseases. However,
they hold many advantages, such as their simple anatomy and small size, as well
as a short life cycle so that a large sample of invertebrates can be studied in
a single experiment within a short period, creating less ethical implications.

The cost of housing them is dramatically cheaper when compared to animals. For
example, thousands of flies could be kept in an enclosure where only few mice
can be kept (Wilson-Sanders, 2011).

Drosophila
is
one of the most expansively studied invertebrates in research (Gilbert,
2008). Its complete genome has been sequenced which allows researchers to
better study molecular mechanisms that cause human diseases. Drosophila require an exceptionally
low cost of care, breeding and screening when compared to mammals. Results from
Drosophila models are quickly generated due a brief life cycle. Another
example of a widely used invertebrate is C. elegans which, like Drosophila,
has a very short life cycle (2-3 weeks), and is cheap to house, manage and
breed (Doke and Dhawale, 2015).

Many experiments
are poorly designed and use statistics that are too basic, often limiting the
statistical validity of the conclusions from the study (Knight, 2011). Because
of this, experiments may have to be repeated, and animals would have been used
for nothing. It is therefore very important ensure a well-designed experiment as
any responsible scientist will want to avoid the wasting of an animal’s life.  

Excessively
large experiments are not only unethical, but are also a waste of scientific
resources. Researchers would benefit from having the smallest sample size that
can still achieve the objectives of the study. If the same number of animals
could be used in more experiments rather than just a surplus wasted in a single
experiment, then scientific output would increase, which, in the long run, saves
animals and scientific resources (Festing et al., 2002).

In order to
keep the number of animals to the minimum necessary and avoid any repetition of
experiments, researchers must have a clear understanding of the objectives of
the study, be able to use appropriate statistical analysis to extract all of the
useful information of the experiment, and interpret the results carefully (Festing
et al., 2002). Solutions could also include training any researchers
involved in experiments that include the use of animals in statistics or the
direct input of statisticians into experimental design and data analysis in
order to achieve better sample sizes (Knight, 2011).

Alternatives to
animal models may be more ethically sound, but they can limit the utility of
the scientific outcomes in a lot of research areas. One such research area is
animal models of human genetic diseases. Animal models are vital for medical
research, as they are used for in-depth investigations of the physiological
basis of different genetic diseases and are of more use than cell culture
studies as some substances that do not produce a response
in an isolated cell will evoke a response in the whole animal (Murphy, 1991) and
therefore show a more
realistic response to drug treatments. Human volunteers would not be an option,
firstly in order to test a hypothesis about a genetic disease and how it develops,
a sufficient number of subjects are needed in order to statistically test the
results of an experiment. Animals for experimentation are widely available and
easy to breed with a short generation time in comparison to humans.  It is much easier to obtain a large sample of
animals to achieve significant results. The conditions in an experiment must be
closely controlled i.e. the
manipulation of one variable while keeping the others constant to observe the
consequences of that change alone. This is easily achieved using animals that
can be kept in the lab, whereas humans may have several factors in their
lifestyle that could affect the results.

On top of this,
with gene targeting, gene knockouts and transgenesis, researchers are able to
be specific about the exact genetic defect they require in an animal model. Without
such models that have been purpose built to possess key genetic diseases,
progress will be very slow or impossible in the development of treatments for
genetic diseases.

Though complete
replacement of animals in experimentation is ethically desirable, it is
unrealistic to expect this to be a reality in every area of scientific research
or education in the immediate future. Although many of the alternatives
discussed in this essay can provide a means to potentially reduce the number of
animals subjected to experiments, it isn’t currently possible for any of them
to completely replace animal experiments. The biggest issue is the difficulty
of creating models that can accurately mirror the physiological systems of
whole living organisms (Festing and Wilkinson, 2007). However, if we make the
assumption that animals are at our disposal to use in research, we must also assume
that we are responsible for ensuring such animals are not unnecessarily put
under any distress, pain or fear and make their lives as comfortable as
possible. It should also be a priority to replace them if at all possible or to
reduce the number needed while still being sure to achieve good data so that
the animals are not wasted.