From Rise of The Planet of the Apes to The Amazing Spider-man to Jurassic Park, the use of animals in scientific research has been a hot topic in more ways than one. However, despite the starring roles that these animals are often given in fiction, real-life animal research has a complicated and sometimes fraught history. The use of animal models in research is so ubiquitous that it is used in every scientific field, from immunology to behavioural sciences. Dogs have helped us understand the principles of behavioural conditioning and sheep have been used to perfect hip prosthetics. Today, we share our lab spaces with mice, rats, fish, flies and pigs without a second thought. But, have you ever considered why we use certain animals over others? Are animal models even necessary given the advancements in technology? How do we choose which animals are most representative to model the research subject we are studying? In dedication to the unsung heroes of the scientific world, here is an ode to animal models.
The earliest uses of animal models in research weren’t used in traditional lab experiments,but rather as models for us to dissect in order to better understand our own physiology. The first recorded use of an animal model in research comes to us from ancient Greece where great thinkers like Aristotle and Erasistratus studied embryogenesis and the cardiovascular system using chicks. There was also Alcmaeon of Croton who was the first to note that the “brain is the seat of intelligence” based on his observations of sensory integration in dogs. However, given that this was 2400 years ago and the technology available to them wasn’t quite as elegant as it is today, there were still misconceptions about human physiology. With the advent of basic surgical techniques, incorrect notions were quickly resolved. In the early 1100’s, Arab surgeon Ibn Zuhr quickly rose through the ranks to become the most well-regarded physician in Spain when he performed the first successful experimental tracheotomy using a goat as his patient. Shortly after, he went on to write a ground-breaking medical encyclopedia called the Kitab al-Taysir. This work of art was the first to accurately describe esophageal, stomach and mediastinal cancers, as well as various inflammatory conditions such as pericarditis. 500 years after that, Dr. William Harvey studied the vasculature of various animals in great detail and documented that not only does the heart function as a pump, but that pulmonary and systemic circulation were separate entities.
As we entered the 1800-1900s, the use of animals in research was beginning to move away from the observational sense, and became more experimental. In the late 1800s, psychologist Ivan Pavlov became famous for discovering the concept of classical conditioning after training dogs to salivate at the sound of a bell by ringing the bell each time they were fed. In the 1920s, UofT’s very own Frederick Banting and Charles Best used dogs to aid in their discovery of insulin and the cells that produce it. They isolated pancreatic islets from one dog and transferred them into another which had had a pancreatectomy. They observed significant and consistent drops in blood sugar following the injection of these cells, leading the monumental discovery that diabetes may be treated with insulin injections. 20 years later, Dr. John Cade discovered the power of lithium salts as an anti-convalescent using guinea pigs. His findings were later extended to the development of antidepressants and mood stabilizers for bipolar disorder. Moving forward another 40 years, the HIV epidemic was at its peak. Thousands of people were dying and the race for a cure was on. Although we still do not have a cure, some of the most important HIV-related research came out of extensive testing conducted on rhesus macaques and led to the development of anti-retroviral drugs as a treatment for HIV.
This would not be an ode to animal models without discussing the incredible role that mice and rats have played in the advancement of nearly every scientific field. In the early 1900s, William Castle began breeding mice to be used in genetic studies. His work was followed by Clarence Little, who perfected the inbreeding of mice in order to create genetic homogeneity. The work of these men meant that scientists essentially had an unlimited stock of research subjects at their fingertips! As tools of genetic manipulation became more advanced, the experimental possibilities became endless. We saw the creation of the Non-Obese Diabetic (NOD) mouse, which was used to understand the pathology of type-1 diabetes. In the 1980s, scientists figured out how to create a knockout mouse, in which a single gene was missing, allowing them to elucidate the purpose and function of that gene. We also saw the creation the Cre-Lox system, which allows certain genes to be turned on or off at a tissue-specific level. Due to these advents, rodents became the indomitable heroes of biomedical research, leading to breakthroughs such as our understanding of how anesthesia works, the improvement of antidepressants, the creation of the SALK vaccine for polio and the production of the meningitis vaccine. Science has relied on rodent models for good reason. They reproduce quickly and in large quantities, they are easy to house and have genetic and biological characteristics that resemble humans quite closely. And with the advent of transgenic and knockout models, we can make these similarities even stronger.
Despite incredible advances in scientific technology, animal models are still required for the development of many therapies. According to Health Canada, clinical trials can only begin once a pre-clinical trial using animal models has shown efficacy and safety of the drug in question. For both prescription drugs and vaccines, animal testing is an obligatory part of the approval process. This means that animal models are absolutely instrumental in our search for new treatments and life-changing cures. As we move into the future and further perfect our gene editing tools, it is likely that we will produce animal models that mimic human disease even more closely. For example, the mouse model of cystic fibrosis is great for studying the gastrointestinal effects of this disease, but does not provide an accurate replica of the pulmonary effects of this disease. As a result, researchers have moved into using genetically engineered pigs as a more accurate model. Even more mind-blowing is the advent of animals which are engineered to express human genes. For example, mice that develop human livers and are used to study how the liver metabolizes drugs and the progression of hepatitis.
The use of animals models in research has been invaluable in our understanding of health and disease. However, unlike what the movies tell us, an Alzheimer’s drug won’t create an army of super-intelligent apes, and the bite from a venomous spider is more likely to kill you than create a superhero. But in this case, maybe it’s a good thing that the old adage of “life imitates art” might be wrong. Maybe the millions of animals all over the world that give their lives in the name of science are the real heroes.
References
1.Barré-Sinoussi, F. & Montagutelli, X. Animal models are essential to biological research: issues and perspectives. Future Science OA 1, (2015).
2.Diabetes: The discovery of insulin. Medicalnewstoday.com (2020). at https://www.medicalnewstoday.com/articles/323774
3.Robinson, N. et al. The current state of animal models in research: A review. International Journal of Surgery 72, 9-13 (2019).
4.Simplypsychology.org (2020). at https://www.simplypsychology.org/pavlov.html
Salma Sheikh-Mohamed
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