Humans have benefited enormously from scientific research involving the use of animals, with virtually every medical accomplishment in the past century reliant on the use of animals in some way. The understanding of the human body has come from more than 200 years of research on the function of normal cells, tissues and organs and also on disease processes. Much of this human body understanding has been facilitated by research that was performed on animals (Royalsociety.org, 2004). Experiment using animals was first started by Greek physicians, Aristotle in 384- 322 BC and Erasistratus in 304- 258 BC. Later in the 129-199/217 AD, Galen also conducted experiments on animals to understand anatomy, physiology, pharmacology and pathology (Hajar, 2011). He was then followed by an Arab physician in the 12th century, who introduced animal testing as an experimental method for testing surgical procedures before applying them to patients. This shows animal experimentation came long way and animals are still being used to study many diseases including diabetes, leukaemia and cancer. However, since the 17th century, debates on the ethics of animal research have raged and as a result, many laws and acts have been passed in many countries to make the animal experimentation more humane. People who support the ban on animal use in research believe that animal experimentation should be replaced with modern methodologies such as in vitro cell and tissue culture, advanced computer modelling and human volunteers. This is because they believe that animal experiments are cruel, expensive and animals are inferior to human beings and they are very different from them so results from animal experiments cannot be applied to human. However, some argue that there have been many cases where animal experimentations have proved necessary in biomedical research and animals are still required for the study of cancer and other challenging diseases. For example, a breast cancer drug called ‘tamoxifen’, which is considered to be one of the most important cancer drugs of all time has helped hundreds of thousands of women’s lives (Scott, 2011). Another targeted drug called imatinib (Glivec), which is used to cure chronic myeloid leukaemia. Both the important drugs have been developed with the aid of animal research. This shows animal experimentations are vital in discovering drugs for infectious or non-infectious diseases and try newly developed drugs and toxicological screenings. Therefore, this essay aims to evaluate both sides of the argument and discuss the alternative methods available to animal use in research as well as areas in which working without animal model could limit the utility of the scientific outcomes.
From the views of those against the use of animals in biomedical research believe that animals should not be used for research and alternative methods must be in place instead of using animals in research. As a result, in recent years a great deal of attention has been focused on the use of alternative methods in research because of concern of the animals’ welfare, the cost increase of animal purchase and care. The alternative to animal testing includes in vitro cell and tissue culture, computer modelling and simulation and research with human volunteers. However, the term ‘alternative’ has created a great deal of confusion. This key term ‘alternative’ suggests that many replacements for animals in many experiments are available. However, in reality, there are few situations in which alternative methods such as in vitro testing and computer modelling are suitable animal replacements and animals will still need to be used for testing of newly discovered drugs and medicines.
Figure 1: 3Rs strategy introduced by Russell and Brunch in 1959. 3Rs strategy stands for Replacement, Reduction and Refinement. Replacement- Animals should never be used if alternative methods are available. Reduction- Researchers must use as few animals as possible without resulting in added unnecessary testing on smaller amounts of animals. Refinement- if animal use is needed guidelines specific to techniques must be followed to avoid adverse impact on animals. (McGillicuddy, 2013). Available at (http://thecityjournal.net/news/research-needed-to-stop-animal-testing/)
Russell and Brunch in their book “The principles of Humane Experiential Technique” in 1959 proposed the 3Rs strategy for use of animal in research. The purpose of the 3Rs strategy is to overcome some of the drawbacks associated with the use of animals in research and avoid unethical procedures. The 3Rs strategy stands for, ‘Reduction, refinement and replacement’ of animal use in research (Ranganatha and Kuppast, 2012). Replacement of animals in research is defined as any scientific method employing a non-sentient material which may replace the use of conscious living vertebrates in animal experimentation. Two types of replacements were distinguished as ‘relative ‘and ‘absolute’ replacement. ‘Relative’ replacement means animals are used but not exposed to any distress or pain during an experiment and no use of animals at any stage of an experiment is identified as the ‘absolute’ replacement strategy. The 3Rs strategy by Russell and Brunch suggested that, there should be a ‘reduction’ in the number of animals used for an experiment animal use for research must be planned very well and carefully ‘refined’ in such way that distress and pain caused during the experiment should be minimised and animals should be ‘replaced’ with alternative methodologies if possible (Doke and Dhawale, 2015).
The reduction is one of the 3Rs strategy introduced by Russell and Brunch in 1959. People who oppose animal use in research would agree that 3Rs strategy by Russell and Brunch provide a means to improve animal welfare until use of animals in research is completely replaced with alternative methodologies. Scientists who accept the need for use of animals for experiments would also agree that it would be preferable not to use animals for testing. Therefore, if animals must be used for an experiment, the section 2 of Animal Act 1986 must be followed. Animal Act 1986 scientific procedure states that the smallest number of animals should be used and there should be consistency in achieving the objectives of the procedure (Legislation.gov.uk, 1986). For example, in vitro cell culture is a good way to screen the compounds at early stages and information about how drugs are metabolised and removed from the body can be collected using the human hepatocyte culture. The inclusion of human hepatocyte culture method in studies helps to remove unsuitable compounds in preliminary stages and minimises the animal use in further experiments (Doke and Dhawale, 2015). Another method is in vitro embryonic stem cell culture and this method reduces the number of live embryos used and toxic compounds towards developing an embryo. Therefore, by using in vitro cell cultures and embryonic stem cell cultures, the number of animals used for experiments can be reduced and also by considering animals of similar age, weight and genetic composition for tests can lower the variability of the animals, so this would not result in misleading negative results.
Refinement is another 3Rs strategy introduced by Russell and Brunch in their book “The principles of Humane Experiential Technique”. Refinement refers to research methods that minimise the suffering, distress, pain or lasting may be experienced by animals during an experiment. Refinement applies to all aspects of animal use from housing to the scientific procedures performed on them (Nc3rs.org.uk, n.d.). Animal facilities should be refined so that pain, stress and discomfort during animal life and scientific experiments can be reduced. Researches proved that any animals under discomfort and stress can lead to an imbalance of hormonal level of animals. This is proven by an experiment using genetically modified mice to study Huntington’s disease. Some mice were maintained in cage environment with the opportunity to nest and hide while some mice were maintained in a barren cage. The result of the experiment was that the Huntington’s disease progressed quickly on mice that were provided with barren cage compared to the mice that were provided with the opportunity to nest and hide. Therefore, this experiment implies that discomfort, pain and suffering can alter animal physiology, behaviour and immunology and such changes would result in variations in experimental results which impair both the reliability and repeatability of the studies (Nc3rs.org.uk, n.d.). Therefore, refinement provides a good model to minimise the stress and discomfort experienced by animals during scientific procedures which will eventually lead to better experimental results and it will also satisfy the people who oppose animal testing.
Replacement is the last 3Rs strategy proposed by Russell and Brunch. The use of the whole animal is a key element of much scientific and medical research as it enables normal physiological processes to be observed within the environment of the living body and helps to identify interactions that control disease processes (Royalsociety.org, 2004). Replacement refers to modern technologies which directly avoid the use of animals in research they would otherwise have been used. Replacement strategy has been divided into two important categories of ‘full replacement’ and ‘partial replacement’. Full replacement means completely avoiding any animals for research. Partial replacement refers to the use of animals that are not considered to be capable of experiencing pain or discomfort. This includes the use of invertebrates such as Drosophila, social amoebae and nematode. Research on eye pigmentation of Drosophila led to the hypothesis that a single enzyme is controlled by each gene (Treherne, 1974). This concept has proved to be crucial to modern molecular biology. Prokaryotes such as Escherichia coli and Bacillus subtilis and protists such as Dictyostelium discoideum are used as a model for molecular and genetic studies and cellular differentiation. Fungi such as Neurospora crassa is used as a model for genetic study as well as for circadian rhythm and studying metabolic regulation.
In recent years, more attention has been focused on designing and carrying out experiments without using animals. There are various suggested alternative methodologies available to use instead of using animals in research. Examples of alternative methods include in vitro testing, microfluidic chip testing, micro-dosing, imaging studies, computer model and simulations. In vitro cell and tissue cultures are used in basic researches on subjects such as cancer chemotherapy, drug research and testing likely toxic substances. In vitro cell cultures are proven to be easy to manipulate and cells can be monitored using microscopes even if the components of the system are adjusted. For example, beating of heart cells can be observed while adding chemicals to the culture medium. However, there are limitations to the in vitro cell and tissue cultures. For example, in vitro cell and tissue culture methods only focus on the cellular level so it cannot replace whole-body testing using animals and animals are required determine the drug safety and efficacy. Microfluidic chip testing is another alternative method to use of animals in research. Microfluidic chip testing is used for the study of biological and disease processes and drug metabolism in the body. Microfluid chips contains tissues samples from various parts of the body that are linked by microchannels through which a blood substitute flows, resembles processes and pathways in the body (Ethics of Medical Research with Animals, 2018). It is proven that microfluidic chip testing provides more complex information than the in vitro cell and tissue culture method. However, microfluidic chip testing has limitations. For example, this method provides less information than testing of the whole body and animals are still required for drug safety tests. Microdosing is another alternative method to the use of animals in research. The main purpose of using microdosing is to test newly discovered drugs. This method enables human volunteers to be safely replaced for animals in drug tests. This method involves supplying humans with doses of a drug that is too low to affect the body but high enough to cause cellular effects. In this way, scientists can monitor how the supplied drug affects the cells. However, the limitation of this method is that, it is considered to be only a phase of a clinical drug trial which is known as the earliest phase of a drug trial. Therefore, testing with a full dose of the same drug, using animals is important so that safety of the drug can be determined. If the drug passes the test, it will be approved for public use. Imaging studies another alternative method that is used to observe the effects of drugs, study brain diseases as well as other neurological disorders. Technologies such as functional magnetic resonance imaging (FMRI), positron emission tomography (PET) and single –photon emission computed tomography (SPET) are used to see inside the body so that effects of the drug can be observed. Limitation of imaging studies is that drug tests using animals are still required to observe the effect of the drug in the body. Therefore, alternative methods such as in vitro cell and tissue culture, microfluidic chip testing, microdosing and imaging studies still rely on the tests using animals and these methods do not completely replace animal testing.
Computer modelling, and simulations is another alternative method to the use of animals in research. Advanced computers and software programs can be used to model the effects of newly discovered drugs and medicines. They can also be used for automobile crash tests and heart studies. Simulations generated using computers are used to predict toxic effects of a chemical or potential drug candidate without using animals. For in vivo experimentations, only the most promising molecules collected from primary screening are used. In vivo experimentations are crucial in predicting receptor binding site of a new drug. Computer software called Computer-Aided Drug Design (CADD) can also help to predict the receptor binding site for a likely drug molecule. Structure Activity Relationship (SARs) is another computer programme, used to predict both binding site and biological activity of a possible drug candidate purely based on chemical molecules attached to the parental compound. Quantitative Structure Activity Relationship is a mathematical description of the relationship between the physiochemical properties and biological activities of a drug candidate. Therefore, with the help of such computer software programmes, the new drug can be modified for the specific receptor binding site, so the number of animals used for drug testing will be reduced. However, animals are still needed to test and collect confirmatory results even though the designed drug is modified for specific receptor biding site. Therefore, the main principles behind these examples of Reduction, Replacement and refinement can be extended or altered to another type of animal research. Reduction strategy seems to be the factor which progress can be made by altering experimental designs and procedures. However, the replacement strategy is very difficult to achieve because of the unique insights provided by use of whole animal and all the alternative methods do require animals at some point of a research to test newly discovered drugs and medicines.
Alzheimer’s disease is the commonest form of dementia and is one of the costliest health problems, affecting about half a million people in the UK today. During the course of the disease, progressive loss of cells from the brain impairs memory and emotions. Currently, there is no cure or effective treatment for Alzheimer’s disease and as more brain cells are lost, symptoms worsen, and it would eventually lead to death (Understandinganimalresearch.org.uk, 2018). Alzheimer’s disease and other causes of dementia are not an inevitable part of ageing but the result of complex brain diseases. The human brain is the most complex living structure and it contains around 86 million nerve cells so recreating this in the research laboratory becomes impossible. The relative inaccessibility of the brain, as well as the slow progression of these diseases, pose even more challenges for scientists who try to study the mechanisms of these brain diseases. Therefore, using animals such as mice, mouse and monkeys for Alzheimer’s disease studies becomes crucial because sometimes working with a living system is the only option and offers the best chances to decode the mechanisms behind the diseases. It is obvious that animals used in research do not show all the mechanisms and features of a complex disease like Alzheimer’s disease, but animals do help to understand some of the key changes. In research labs, flies and mice were bred to develop amyloid and tau in their brain and it has been crucial in understanding the proteins involved in Alzheimer’s hallmark. By developing amyloid and tau, scientists were able to track how these proteins develop and discover clues to why these proteins build up could be so damaging (Alzheimersresearchuk.org, 2018). Flies and mice can also help to unravel the disease genetics that causes dementia. Flies and mice are genetically modified and bred to develop the features of the diseases within a short period of time. This is because most of the important genes found in humans are also found in equivalent animals. This makes them invaluable because important insights into the disease can be gained in a short period of time. Using animals to identify the basic biological processes that go wrong in dementia is important as it could lead to the discovery of new treatment targets and potential new drugs for the disease. It is a law that any new treatment designed for human disease, they must be tested in animals first. By testing new treatments in animals help to highlight the potential side effects and make sure more money and time are invested in developing new drugs. While drugs may not behave the same in animals as they would in Alzheimer’s patients, testing on animals helps to decide whether the new drug should be taken into clinical trials. The drugs developed for the treatment for dementia, were first tested using animals. However, the drugs approved for clinical testing are not a cure for the disease as currently, they are the only treatment option available for people with Alzheimer’s disease which allows the patients to live with symptoms and maintain their quality of life. Therefore, research using animals continues to be vital in the ongoing search for a treatment for diseases such as Alzheimer’s and dementia that can stop or slow the diseases. If animals were not used for Alzheimer’s disease or dementia, it wouldn’t have been possible to understand the mechanisms behind the diseases. To identify the exact cause of dementia or Alzheimer’s, scientists still depend on the use of animals. Researches suggest that new therapies for dementia are showing promise in animal studies. Therefore, use of animals in further experiments to identify the cure is crucial along with the technological methodologies.
Overall, modern biology and many of its contributions to the well-being of society is heavily dependent on the use of animals in research. Animals play a unique role in research as models of human demonstrate the important role played by animals in future researches. In the discussion of the processes from discovery to treatment drug, it was proven that although animal alternative methods do have utility in some research areas, most of them have been accomplished through the use of animals (Royalsociety.org, 2004). The point was then reiterated in the discussion of the 3Rs strategy by Russell and Brunch, where all three Reduction, Refinement and Replacement were discussed with examples. The 3Rs strategy demonstrates that every effort must be made to use as few animals as possible, use of animals in research must be planned very well and refined carefully in a way that distress, pain and discomfort caused during an experimental procedure should be reduced and if possible use of animals should be replaced with other alternative methodologies. However, it becomes clear that use of animals in research can never be fully replaced by alternative methods because, at some point of an experiment, a new drug must be tested in animals to observe any side effects. It is a law that any drugs or medicines created for diseases must be trialled on animals first. Therefore, use of animals in research is necessary to test newly discovered drugs and medicines that could potentially treat diseases like Alzheimer’s and cancer.