Animal Experimentation: A Continued Necessity in Medical Research

Katie Loughman, Kathryn Brebner, Emily Mei 

Introduction

World War II is often referred to as the bloodiest war in history. From 1939 to 1945, over 50 million soldiers and civilians lost their lives to bullets, bombs, lethal gases, or the horrifying and systematic genocide of the Jewish people (History.com, n.d.). Families were torn apart by loss both on and off the battlefield. But what most fail to realize is that many of these deaths were not caused by the weapons themselves, but instead by the bacteria that colonized the wounds that they inflicted. In the midst of this devastating period of history, there was a beacon of hope: the development of penicillin, which is still regarded today as the greatest achievement in medical history.

The mold Penicillium notatum, first discovered by Alexander Fleming in 1928, was finally refined and applied to the use of treating infections in humans near the end of WWII and was soon sent out to the front lines en masse (understandinganimalresearch.org.uk, n.d.). Before it ever made its way into humans, this pioneering antibiotic was tested extensively on mice through the use of what is known as the mouse protection test. During this test, a given number of mice were injected with lethal doses of bacteria. Half of these recipients then received the refined penicillin. In testing, the mice that received the antibiotic survived their infections while the others died (understandinganimalresearch.org.uk, n.d.). This testing was essential to determining that not only was this drug effective at killing bacteria, but that it could do so without toxicity to the host (discoveriesinmedicine.com, n.d). Armed with penicillin, we could now wage war on this new battlefield against bacteria. Soldiers with grave wounds who often waited an average of 14 hours to see a surgeon could now be treated with penicillin to prevent lethal complications of infections such as septicemia and gangrene (discoveriesinmedicine.com, n.d.). Thanks to animal research, countless soldiers who would have otherwise died were able to make it home to their families.

Background

The use of animal experimentation dates back to the time of the Ancient Greece, where philosophers and scientists such as Aristotle used animal models to better understand the anatomy and biology of a living organism (Hajar, 2011). In more recent times, researchers have used animal models to improve their understanding of how manipulating body systems with drugs or therapies can alter the health and well-being of the organism. In this way, animal research has become essential to the medical community for the development of new medicines, therapies, and surgical techniques. However, over the course of history many have argued against putting living organisms through pain and suffering for the benefit of human-kind. Many animal rights groups, such as PETA, or the People for the Ethical Treatment of Animals, take a strong stance against the use of animals in laboratories (peta.org, n.d.).

In response to the strong backlash to animal use in research, the government created new laws to give some protections to animals. The first major legislation to protect animals was the Animal Welfare Act, which was published in 1966 (Favre, 2002). While this law, which is enforced by the USDA and APHIS, improved animal well-being by dictating and enforcing the proper use, housing, and methods of acquisition for many animals, it does have some major pitfalls. It excludes rodents, birds, reptiles, and all animals used for food and fiber (Favre, 2002). Since 90% of the animals used in research are rodents, these laws do not lend them any protections (Kehinde, 2013). In order to combat this, “The Guide for the Care and Use of Laboratory Animals” was published by the National Research Council and is still considered to be the standard of laboratory animal care today. This “Guide”, which is highly respected in the research community, covers the well-being of animals like mice and rats, as well as their proper housing, care, pain management, and even humane euthanasia (NRC, 2011).

Scientists are often motivated to maintain high standards of welfare because failure to do so could put the animals in a state of extreme stress. The hormones and physiological changes associated with stress can seriously interfere with experimental results. One example of a welfare recommendation made by “The Guide”, as it is better known as, states that animals used for research purposes should be housed to maximize species-specific behaviors and minimize behaviors caused by stress. For example, animals that typically live in groups in the wild should be housed in either pairs or groups to meet its needs and social requirements (NRC, 2011).

Despite the efforts that have been made to improve the lives and minimize the suffering of animals, many groups like PETA are still very much against their use in medical testing. While their stance comes from a commendable place of compassion for animals, it often becomes problematic when put into play in the real world. In order to better understand the reasoning behind PETA’s stance against animal use, we must first begin to understand that there are two major schools of thought when it comes to animal ethics.

Animal rights groups like PETA operate under the conviction that all animals have equal rights to humans and should be treated as such. They argue that animal use in any capacity that benefits humans is unethical and thus should be eliminated. In PETA’s own words, “Animals are not ours to eat, wear, experiment on, use for entertainment, or abuse in any way” (peta.org, n.d.). This includes not only animals in research, but also animals that are used for food and fiber, and animals kept as pets or for recreational purposes such as dogs or horses.

Another major school of thought in animal ethics is animal welfare. Animal welfare activists support the use of animals in research, but instead argue that in order to use animals for our benefit we must be actively championing for their well-being. According to the American Veterinary Medical Association (AVMA), “ensuring animal welfare is a human responsibility that includes consideration for all aspects of animal well-being, including proper housing, management, nutrition, disease prevention and treatment, responsible care, humane handling, and, when necessary, humane euthanasia” (avma.org, n.d.). Animal welfare in recent years has been implemented in many ways, such as in “The Guide” described earlier.

One other way researchers are implementing the ideals of animal welfare is through the concept of the Three R’s of animal welfare. They refer to replacement, reduction, and refinement. The goal of each respective “R” is to replace animals with non-living models when possible, to reduce the total number of animals used, and to refine the experiments so that animals are receiving the best welfare possible (Hajar, 2011). Using the three R’s helps in attempts to reduce animal suffering and to yield the best results with as few animals as possible.

Arguments Against Animal Models

Animal rights activists often argue that there are many non-animal research models that are just as effective as using animals, and thus, animals are no longer necessary for the development of new drugs or medicines (peta.org, n.d.). Although there is truth to the fact that there are alternatives to using animals in research, they are not necessarily effective or accurate. One alternative method that has been used by researchers today is in vitro. By definition, in vitro refers to an experimental process that occurs in a test tube, culture dish, or anywhere else beside the living organism (Kehinde, 2013). In the article “They See a Rat, we Seek a Cure for Diseases: The Current Status of Animal Experimentation in Medical Practice”, published in Medical Principles and Practice, Kehinde argues that there are serious limitations to using in vitro research as opposed to testing on animals. He argues argue that while in vitro experimentation is cheaper and easier for the researcher, the data obtained is often inadequate (Kehinde, 2013). Results that are obtained from in vitro experimentation are often inaccurate due to the fact that cells have evolved over time to work in tissue and organ systems; therefore the way they react outside of the body may differ from how they’d react in vivo, where they are in the context of all other organ systems (Kehinde, 2011). Researchers have used animals in research to test diseases and vaccinations for such diseases. By testing these drugs on animals, they are able to determine how the body as a whole will respond to the drug as opposed to just a small portion of tissue used in vitro (Kehinde, 2013).

Recently, in silico research techniques have also caught the attention of animal activists as a proposed alternative to animal experimentation. In silico is a term that refers to a procedure or experiment that’s performed through a computer simulation. Although this is indeed a potentially useful alternative, much like in vitro it has its inherent limitations when it comes to producing accurate results. In their paper “In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling” Dr. Thomas Hartung and Dr. Sebastian Hoffmann (2007) argue that, like in vitro, using in silico experimentation first requires a large set of data retrieved from organisms in vivo (or experimentation on an organism as a whole). They continue to argue that the use of in silico methods require a large group of live animal trial runs to be carried out in order to validate the credibility of each experiment. They state, “While for in vitro tests only 20 to 100 substances are required for validation, a much larger training set of data is necessary for in silico methods.” (p. 159) This is not a realistic alternative to animal testing because for each experiment it requires a large number of tests to be run on live animals before it can even begin to work. Additionally, much like in vitro testing, it happens outside of the context of a living organism and results are risky to interpret as being safe and valid enough to move to human trials.

Those opposed to animal research may also claim that it’s simpler to go straight to human clinical trials for certain drugs and therapies. Aside from ethical and safety considerations, there are experimental limitations to human trails that become problematic. According to Kehinde (2013), in human trials of new drugs, approximately 3,000 human volunteers would be required for accuracy of results (p.56). But, if a latent side effect were to occur after the clinical trial in 1 out of 10,000 patients, the drug would already be on the market and would have affected countless individuals (Kehinde, 2013, p. 56). This is a serious safety concern. One example of how this method of experimentation can go wrong is with the drug Actos. Actos was used for the treatment of diabetes mellitus, and underwent this type of clinical testing. It wasn’t until it had been on the market for 8 years and used by over 1 million people that it was discovered to increase the incidence of bladder cancer (Kehinde, 2013, p. 56). This is why animal models in the early stages of drug development are so essential to determining a drug’s safety.

Additionally, animal rights proponents generally also argue that our current knowledge of biology and medicine should be sufficient to build upon to create new therapies. However, as described by J.H Botting and A.R Morrison in the article “Animal research is vital to medicine”, from the Scientific American, animal research has been and continues to be essential to the development of new techniques (1997). One example that shows the importance of animal testing to develop new or unique therapies is in the development of mitral valve replacements used in open heart surgery. Botting and Morrison (1997) state that effective replacements for heart mitral valves have “stemmed from years of development and testing for efficacy in dogs and calves” (p. 85) and that, “critics of animal research cannot present a convincing scenario to show how effective treatment of mitral valve insufficiency could have developed any other way” (p.85). Since it’s unethical to test these untried procedures on human beings, testing the transplant procedure in these dogs and calves gave us a more accurate picture of the likelihood of success before it was attempted in humans. Without developing this therapy in animals it would likely have either never been made available to people who would die without the replacement, or human beings may have died in an attempt to find a safe and effective way to perform it without an animal model.

Benefits of Animal Research                                                                                                          Animal research is so important to the betterment of mankind in today’s world, because through the development of new drugs and therapies we can hope to combat terrible diseases that cause suffering or death to human beings across the globe. One way that animal testing contributes to this medical advancement is through the development of novel methods to treat cancer, a disease that kills millions of people every year. As described by Budhu, Wolchock, and Merghoub in their article “The importance of animal models in tumor immunity and immunotherapy”, published in Current Opinion in Genetics & Development, one method being explored recently by researchers is immunotherapy of cancer. In essence, immunotherapy utilizes the natural ability of the body’s immune cells to target and attack foreign cells. Using drugs, researchers are beginning to manipulate the immune system to better recognize tumors as foreign, and stimulate the destruction of tumors by immune cells (Budhu, Wolchock & Merghoub, 2014). The authors claim that the use of mice in research has had a major impact on the understanding of cancer immunology and in the development of currently available cancer immunotherapies. By using mice that have transplanted tumors we can study the effects of these drugs on the tumors and on the body as a whole without needing to test on human cancer patients (Budhu, Wolchock, & Merghoub, 2014). With the relatively new and exciting development of “humanized” mouse models, in which the mouse’s own immune system is removed and replaced with human immune cells, any data acquired from these mice become more directly applicable to humans (Budhu, Wolchock, & Merghoub, 2014). This has far reaching implications on the effectiveness of animal models to predict adverse side effects in humans. These new concepts have been applied to formulate approved human therapies such as ipilimumab, which successfully targets advanced malignant melanoma, an extremely aggressive and often fatal cancer. These immune therapies described are now on the forefront of cancer research due to their high rates of success in cancer patients. Without the animal models used here, this major advancement and benefit to society would not have been possible. This gives us a renewed hope in the fight against cancer.

Some activists argue that using animals for medical research isn’t very effective in developing beneficial drugs or therapies for humans. However, there is a great deal of evidence to the contrary. Through the use of animals in research, mankind has made great strides in medical advancement. One of the most important discoveries we’ve made through animal testing is the development of vaccinations. One of the greatest recent discoveries was the vaccination for Polio disease, which was made possible due to animal research. According to the American Association for Laboratory Animal Science Foundation, over 21,000 cases of Polio infected the US in 1952, which caused paralysis that left children unable to breathe without the use of an iron lung, or even death (aalasfoundation.org, n.d.). Animal models using mice and monkeys were used to develop an effective vaccine and in the late 1950’s polio was nearly eliminated (understandinganimalresearch.org.uk, n.d.). Today polio has been nearly eradicated with the exception of a few remaining cases in 16 countries (aalasfoundation.org, n.d). This is all thanks to the development of vaccines using animal models.

Humans undoubtedly benefit from the use of animal testing, but what many don’t consider is that animal research directly feeds back to benefit the animals themselves. Canine parvovirus has historically been serious problem in the veterinary field, and in 1978 a worldwide outbreak was wiping out our dog population (aalasfoundation.org, n.d.). Researchers soon discovered that parvovirus was very similar to feline leukemia seen in cats. A vaccine had already been discovered to successfully prevent feline leukemia, and with a few modifications a new vaccine was created, tested, and put into use to prevent canine parvovirus (aalasfoundation.org, n.d.). In today’s world, parvo, while not completely eradicated, is far less prevalent than is has been historically, and outbreaks are usually caused by owners that refuse vaccines. The discovery of a vaccine for parvovirus is ranked as one of the best success stories in the veterinary community and it was due in part to the animals used in the development of both the feline leukemia vaccine, and in the parvovirus vaccine. This benefit to animals is true of most medical advances that involve animal testing. If we make improvements in human medicine, these concepts often filter down and are applied in veterinary medicine in the form of better medicines, vaccines, and surgical techniques that save animal lives every day.

Looking Forward

In order for the field of medical research to continue creating new approaches to fighting disease in humans, there needs to be a shift in the general opinion towards animal research. Currently, much of the public has been influenced strongly by highly publicized media campaigns by animal rights activists like PETA without knowing all of the facts. As a consequence most of the general public is very much against animal research without understanding just how essential it is. A new non-profit organization is needed to educate and change negative public perceptions about the use of animals in medical research. Without this change in how society thinks about animal research, advances in medicine may be suppressed to the point that human and animal lives may suffer for the lack of new medicines and therapies it would cause.

Due to the overwhelming success that groups like PETA have had in getting their message out to the public, we plan to adopt a similar model to share our ideas. We propose to form a new non-profit organization called The Society for the Welfare of Research Animals (SWRA). This animal welfare based non-profit organization would focus on disseminating facts and knowledge about the positive aspects of animal research, and what can be done to continuously improve the wellbeing of the animals involved. As a non-profit, we would run on donations and volunteer work. We will utilize celebrity endorsement and media campaigns to spread knowledge about the conditions that animals used in research are living in. In this vein, we would like the celebrities we work with to appear on popular talk shows or news stations, on billboards, and in magazine advertisement. While our organization is modeled after PETA’s success, we would avoid the extremism and propaganda they often employ to influence the public opinion.

Additionally, we would encourage open discussion with prominent members of the research community about what techniques they are using to test on animals, and what they are doing to actively improve the lives of the animals that they use. Many researchers feel that they can’t discuss their work with the public for fear of condemnation or even physical harm, when in reality, the work that they do could potentially be applied to saving lives. In conjunction with educating the public about animal research, we would like to assist in creating avenues by which researchers and the public can openly communicate their ideas and concerns. If the public was more aware of what is really happening in these labs, not only would it ease some of the fear of the unknown, but it would also hold researchers to a higher standard of accountability for the welfare of the animals that they use.                                                                                                  We will also encourage involvement of the public by establishing campaigns to continually improve the legislation that affords protections to animals used in research. We recognize that while animal research is necessary and often leads to life-changing medical advancements, it’s not a perfect system. “The Guide” certainly sets standards of care for rodents, but under the law there is still no legal accountability or government enforcement for the use of rodents. Better accountability for rodents is an example of something that we could strive to change with the help of the public. We would support the development of new legislation that would improve the quality of life of research animals and more strongly enforce welfare practices without hampering the scientific process.

In conclusion, animal research is essential to the medical community for the development of new therapies, vaccines, and drugs. Without it, we would be plunged back into the medical Dark Age that we experienced before the advent of modern medicine. It’s easy to become complacent and forget that less than a century ago, we lived in a world without antibiotics. Imagine if Penicillin had never been accidentally discovered and put to good use. Your family, friends, and even you would be living in danger everyday of picking up the pathogen that ends your life. While we take for granted the ability to go to the clinic and get a bottle of antibiotics and be on our way, it wasn’t always the case. With resistance rapidly growing in microbes and outpacing even our best drugs, we need to support animal testing now more than ever. There will be a day when our antibiotics stop working, and we will need to rely on the scientific community to find a new way to save lives, and they can only do this with the help of animal models. Animal research saves lives every single day through the advancements that is has given rise to. So in closing, remember to thank a mouse.

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