By Annagh Devit, Fall 2020.
The air pump experiment and the flowerpot technique are two innocuous sounding procedures that hide their horrors behind their names. In the air pump experiment, a small animal is placed inside a sealed glass container and the air is slowly removed, extinguishing the animal’s life like a candle flame[1]. The first instance of the flowerpot technique placed cats on an upturned flowerpot surrounded by water, depriving them of REM (rapid-eye movement) sleep over the course of 17 days. The experiment ended when the cats died be it from drowning or lack of sleep[2]. While the air pump was popular in the 18th century, the flowerpot technique was created in 1967 and is still used today. Without doubt, animal welfare in research has greatly increased in the modern era, but the ethical reasoning for the use of animal subjects has not changed in the last 200 years. With the emergence of new biological techniques, it is more important than ever to reexamine the utilization of animals in research so future generations will not look back at this era with the same revulsion that we hold towards the past.
There are two primary arguments for utilizing animals in research: it can enhance human life and it can limit the negative outcomes from products destined for human use[3]. Louis Pasteur’s inoculation of chickens with chicken cholera was a utilization of animals for humanity’s benefit (leading to the field of immunology) while his testing vaccines on animals was a method to limit adverse human outcomes[4]. Nothing is inherently wrong with these arguments: however, it is important to understand how they came about and how they become justifications for unethical research.
Both reasonings originated with Aristotle in the 4th century BCE. His treatise “On the Soul” introduces the Scala Naturae — a “Natural Ladder” — that ranks all living organisms, with plants at the bottom, animals in the middle, and humans at the top. He believed that “plants are created for the sake of animals, and animals for the sake of men”[5]. The idea that animals existed purely for human utility was a popular argument in the 18th century for physicians’ and scientists’ rights to vivisection. These live dissections, usually on street dogs or other accessible animals without any type of pain mediation, served little practical benefit. Rather than leading to new discoveries, they were used to teach medical students the circulatory system — something that can be accomplished through other means[1]. However, contemporary scientists argued that the progress made in this century was on account of such new practices like vivisection; hence, to abolish the exercise would be akin to stomping out the Age of Enlightenment.
Both vivisection and its reasoning that animals are meant to be utilized by men softened in the later centuries but both continued to be utilized. For example, in ethical clearances, researchers should only use animals if it is “an unavoidable situation”[6]. In other words, the reasoning for vivisections—that they provide human benefit—is no longer accepted on such vague terms. While Aristotle’s belief that animals exist solely for human benefit is no longer widely accepted, his natural ladder remains ever present. The regulation of animal welfare, most notably the Animal Welfare Act (AWA), relies on the classification of animals. In general, the closer the animal is to humans, the greater the protections. The AWA, for example, only includes certain mammals (non-human primates, dogs, and cats among others) and notably leaves out lab rats and mice[7]. Ethical clearances for research animals are also generally applied to warm blooded vertebrates leaving virtually no restrictions on widely used model organisms like D. melanogaster and C. elegans. Protecting the welfare of some animals and not others, means that some animals are more valued than others—the exact premise of Aristotle’s ladder. While such a position might be agreeable, there is no scientific rationale behind the hierarchy. Fish, birds, reptiles, and rats all feel pain. Furthermore, traits that Aristotle would consider solely human, like the use of reason, have been displayed in such evolutionarily distant animals like octopuses. The flaws in these regulations reveal that restrictions were not put in place with any type of rationale but rather due to human biases that preferred testing to be done on pests rather than pets.
The major work advancing the ethical use of animals in research focuses not on a particular animal’s identity but rather broadly applicable guidelines for minimizing pain and increasing overall quality of life. Louis Pasteur was one of the first scientists to use humane endpoints in his experiments[1]. Such endpoints are “one or more predetermined physiological or behavioral signs that define the point at which an experimental animal’s pain and/or distress is terminated” [8]. In a nonetheless controversial procedure, Pasteur infected rabbits with live rabies in order to harvest a modified version of the virus for a vaccine. For the procedure to work, the rabbits needed to be infected and show symptoms: however, they did not have to succumb to the disease. Therefore, Pasteur decided to chloroform the rabbits after showing symptoms to prevent unnecessary suffering. More recently, USDA guidelines (which are used in most research laboratories) also try to establish categories based around pain for regulation. Another common practice is the “Three R’s”: Replacement, Reduction, and Refinement. It instructs researchers to replace the use of animals when possible, reduce the number of animals to minimum needed for valid results, and refine the experiment to limit suffering as much as possible[7]. While all of these guidelines are much more useful than the mammal-centered approach of the AWA, there are merely guidelines. It is difficult to enforce the Three R’s approach: Who can really say if an experiment will have the same effects in vitro as in a mouse model? Furthermore, the USDA guidelines are subject to misinterpretation and misreporting. The ethical determinations of research are then left in the hands of individual scientists and institutions, which as seen through history can permit egregious errors.
The future of animal modeling remains unclear. The rise of effective in vitro replacements might replace animal testing altogether. Alternatively, advances in humanized immune systems — specifically mice with engrafted human tissues — might bolster the use of lab animals[9]. Perhaps this new therapy could humanize mice in more ways than one. What remains clear is that a review of core ethical criteria and how it is applied is needed so that future generations will not look back on today with the same disgust as we view the animal experiments of the past.
[1] Henrique Franco, Nuno. 2013. “Animal Experiments in Biomedical Research: A Historical Perspective.” Animals 3(1), 238-273. https://doi.org/10.3390/ani3010238
[2] Banyard, Philip and Flanagan, Cara. 2006. Ethical Issues and Guidelines in Psychology. Routledge.
[3] National Research Council (US) and Institute of Medicine (US) Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research. “Use of Laboratory Animals in Biomedical and Behavioral Research.” National Academies Press (US); 1988. 3. https://www.ncbi.nlm.nih.gov/books/NBK218273/ doi: 10.17226/1098
[4] VBI Vaccines. 2016. “Louis Pasteur and the Development of the Attenuated Vaccine.” https://www.vbivaccines.com/wire/louis-pasteur-attenuated-vaccine/
[5] Francione, Gary. 1995. Animals Property and the Law. Temple University Press.
[6] Pasupuleti, Mohan, K., et al. 2016. “Ethical Guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.” Journal of Indian Society of Periodontology 20(4), 360-368. https://www.jisponline.com/text.asp?2016/20/4/360/186931
[7] Rowan, Andrew N., et al. (1995). The animal research controversy: protest, process & public policy: an analysis of strategic issues. North Grafton, MA: Center for Animals & Public Policy, Tufts University School of Veterinary Medicine.
[8] PennState Senior Vice President for Research, “Humane Endpoints in Animal Research.” https://www.research.psu.edu/animalresourceprogram/experimental-guidelines/humane-endpoints#:~:text=Humane%20endpoints%20refer%20to%20one,treatment%20to%20relieve%20pain%20and
[9] Allen, T.M., et al. “Humanized immune system mouse models: progress, challenges and opportunities. Nature Immunology 20, 770-774. https://doi.org/10.1038/s41590-019-0416-z