Behind the Lab Doors
The medical applications of animal testing
—By Sabrina Xue and Brienne Bordes
Animal testing. One of the most divisive ethical debates both inside and outside the medical community. Some claim that the animals suffer extreme pain and neglect, subjected to invasive research, cosmetic testing, and drug approval processes. Yet, across the world, millions of people are breathing, walking, and existing due to those same animals. From the polio vaccine to a possible cure for breast cancer, animal testing has created significant strides in medicine, saving countless lives in the process. Animal research plays a critical role in the medical and scientific fields, allowing scientists to better understand biological processes and discover effective treatments and novel medical advancements that allow people to live a better quality of life.
As a renowned research institution, the University of Michigan itself has experienced much of this debate and has thus created a strict set of rules and regulations to promote the most ethical form of animal testing. However, despite its best efforts, there are still letters of protest filling President Santa Ono’s mailbox as U-M research facilities allegedly fail to comply with these guidelines.
University of Michigan rules and regulations
According to Science, Medicine, and Animals, published by National Research Council, in their article, “Regulation of Animal Research,” the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS policy) set standards for humane care and use of laboratory animals by requiring research facilities to comply with the Guide for the Care and Use of Laboratory Animals. This guide ensures that animals are treated with respect and care through guidelines for veterinary care, housing, nutrition, and handling. Specifically, it advocates for the “Three Rs”: Replacement of animals with alternative methods when possible, Reduction in the number of animals used, and Refinement of procedures to minimize distress.
As a research-oriented educational facility, the University of Michigan has had to create a strict set of regulations supporting national laws such as the PHS policy to manage the ethics of animal testing in its work. Primarily, The Animal Care & Use Program was created in pursuit of “impactful science to benefit both human and animal health,” with a focus on “upholding the highest animal welfare standards in all aspects of research and instruction.”
The program claims to not only embrace the “Three Rs” but also “go beyond strict adherence to all required guidelines.” In attempts to achieve this, the program created three units to support campus-wide research while maintaining ethics: the Animal Care and Use Office (ACUO), the Unit for Laboratory Animal Medicine (ULAM), and the Institutional Animal Care and Use Committee (IACUC).
Department of Surgery surgical fellow Jensyn VanZalen from the Extracorporeal Life Support (ECLS) Lab comments on the prevalence of the IACUC within the lab: “We have to follow it. It’s incredibly important for us and anybody in animal research to adhere to the guidelines.”
The other two units—the ACUO and ULAM—mainly work to support the IACUC and the animals being used within research programs. The ACUO works to review programs while ULAM trains laboratory animal veterinarians to support the U-M research community and the animals under their care. These two programs together assisting IACUC help ensure that laboratory animals are cared for. U-M researchers such as VanZalen recollect experiences seeing the services provided by ULAM in their research.
“We’re really regulated by ULAM…. Vets are constantly checking in on them once a day to make sure that we’re taking care of them properly, and we never use an animal that isn’t feeling their best,” she said.
The rules applied: University of Michigan’s ECLS lab
Michigan Medicine is heavily incorporated with many labs at U-M, and these research labs produce a variety of advancements in the medical field. However, to effectively conduct research, many U-M labs rely on animal testing before applying the research to clinical settings.
One of the major labs at U-M is the Extracorporeal Life Support (ECLS) Lab, which studies life support and artificial organ research and technology development. Led by Research Investigator Alvaro Rojas-Pena, MD, the lab aims “to save patients suffering from acute cardiac, respiratory, and other organ failure and improve their quality of life.” The research utilizes ECLS technology, specifically the use of extracorporeal membrane oxygenation (ECMO), which was developed by Laboratory Director and Professor Emeritus Robert Bartlett, MD around 50 years ago. The lab’s research is testing modifications of ECMO systems and artificial organs which have been applied to various clinical applications.
Most labs at Michigan and other universities study medicine at the molecular level. “You start with cells and the products of cells and study things, at the RNA, DNA level in those cells,” said Dr. Bartlett. However, the ECLS lab is unique in the fact that they use large animals to effectively produce results that can be applied to humans. The devices “have to be tested on animals with approximately the same size and physiology of humans.” Dr. Bartlett further emphasized, “It’s rare to have large animal research facilities going on. There are only a dozen or so in the whole university. Anything bigger than a mouse is considered old-fashioned. So we’re very old-fashioned.”
The ECLS lab follows all the University’s protocols regarding animal research. All volunteers and students entering the ECLS lab are required to complete multiple modules and workshops through U-M and Michigan Medicine to have direct contact with the animals in the lab. These modules educate participants on the U-M animal protocols and instructions on how to care for specific animals the lab uses as well as HIPAA regulations. The workshops that students and volunteers partake in also ensure they have the necessary knowledge to properly provide fluids and medications to the animals and care for the animals in general.
Furthermore, all ECLS staff, students, and volunteers show care and love towards the animals that are being studied. The animal subjects are always treated when showing signs of pain and are given toys or objects of enrichment that the animal can play with at all times. VanZalen said, “The pigs love fruit snacks, so every time we go in there and check on them, I always give them a fruit snack or marshmallows.”
U-M Junior Ishika Talreja is a volunteer at the ECLS lab and has had direct contact with animals in various research projects in the lab. She said, “I think the animals are treated with a lot of kindness and respect. Everyone is always making sure they are not in any kind of pain, and the fellows don’t hesitate to end the prep if they think the animal is in pain or discomfort.”
The lab never allows the animals to continue in pain if nothing more can be done. Dr. Rojas-Pena explained, “We have created a scale to objectively assess pain in the animals, and we have interventions based on that score system. We use a list of humane endpoint criteria, so when the animal has pain that cannot be controlled and is suffering, the animal is euthanized.”
The staff and volunteers care heavily for the animals and even give them names at the start of each PREP. Talreja added, “Something we always do as a gesture of kindness is before euthanizing the animal, the lab members present in the room will say goodbye and thank the animal for its contribution to medicine and how grateful we are for their help.”
Saving the human life
While the plethora of ethical issues poses a justifiable deterrent to the use of animal testing, the results of such a practice cannot be denied. A non-departmental public body sponsored by the Department for Science, Innovation, and Technology called the UK Research and Innovation summarizes the general claim of animal-testing supporters. “The use of animals in biomedical research helps researchers better understand the biological processes that are central to our health. This is essential for developing safe and effective ways of preventing or treating disease.”
Undergraduate research students at the University of Michigan share the same sentiments, as they also partake in animal testing for research purposes. U-M freshman Madeleine Fournier, who is a student in the Undergraduate Research Opportunity Program at the ECLS lab, works hands-on with animals in a surgical setting. Fournier states, “I think that especially in surgical research, the use of animals is essential to making advancements.”
Animals are often used in medical research with other methods like human trials and computer simulations when other methods don’t provide enough information. According to the University of Oxford, “A living body is an extraordinarily complex system. You cannot reproduce a beating heart in a test tube or a stroke on a computer.” Thus, animal models are used in response to the ethical constraints that limit certain types of research on humans. These models allow scientists to control variables such as diet and environment, which then helps to advance their understanding of complex biological processes.
Fournier gives a reason for this, “It isn’t ethical to test ideas on humans initially without any idea how procedures, ideas, or inventions will affect lives, and there isn’t a way to replicate surgical procedures similarly to reality unless animals are used. Although sad, using animals is the closest we can get to understanding improvements to change the practice of medicine and allow the field to grow to help save more individuals in the future.”
According to Stanford Medicine, life span is another reason why animal testing is so effective in medicine aside from their biological similarity to humans. “Animal models can be studied throughout their whole life span and across several generations, a critical element in understanding how a disease processes and how it interacts with a whole, living biological system.”
In practice, animal testing has allowed for significant strides in medical history, recently with the COVID-19 vaccine trials. This notable medical achievement was accredited to animal testing by the UK Research and Innovation Organization in its article, “Medical Breakthroughs Underpinned by Animal Research.” Animal testing was used in every step of the development process, from ferrets and non-human primates being used to help engineer a spike protein to mice and pigs currently being used to help create a new potential vaccine (RBD-SpyVLP).
These advancements are further demonstrated by Julianna Hickey, a U-M undergraduate student, who does clinical research in the U-M School of Kinesiology and studies the movement of humans. Although she does not work with animals, she has seen the results of animal research reflected in clinical settings. Hickey says, “I think animal research is necessary in medicine because a lot of treatments for humans that have been developed started with testing them on animals. For example, the development of hip replacements started with animals, and now hip replacement surgery is super common and allows people to have a better quality of life.”
Not only has this practice allowed for advances in human medicine, but it has also helped increase animal healthcare. Hundreds of drugs and treatments developed for human use are now routinely used in veterinary clinics as well, helping animals live longer, healthier lives. Some examples include antibiotics for bacterial infections, chemotherapeutic agents for cancer treatment, and insulin for diabetes management in pets like dogs and cats. Although initially intended for humans, these medicines are also commonly used in veterinary medicine to help animals lead more comfortable lives.
The dilemma of animal testing
Double-board certified neurologist Aysha Akhtar raises concerns about the reliability and predictive value of animal research for human results and interpreting human physiology in “The Flaws and Human Harms of Animal Experimentation.” She describes how animal experimentation can steer the resources away from more effective methods of testing. She emphasizes that “The collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.”
Sophia Ramirez, a senior in the U-M School of Public Health who upon graduation is working in direct patient care, opposes animal testing for several scientific reasons. She stated, “Animal experimentation, regardless of what it’s for, fails to reliably inform human health.” The National Library of Medicine explains that this lack of reliability is due to the effects of the laboratory environment and other variables on study outcomes, disparities between animal models of disease and human diseases, and species differences in physiology and genetics. Ramirez further said, “There are differences between animals and humans, and the same disease often presents differently in each organism. Each species is different in their physiology and genetics.”
However, Dr. Bartlett challenges the idea that the anatomy and physiology of animals is too different from humans to apply the research to clinical practice. “The anatomy is not a problem. Most mammals have the same anatomy as humans. So the heart, lung, and gut, and brain, all the way from mice up to gorillas or baboons is all basically the same.” The research from the ECLS lab is going towards developing artificial organs, and the biggest problem is the clotting that occurs. “We pick an animal where the clotting system is either most similar to humans or more challenging than humans, so if you can do it in that animal, it ought to work in a human,” said Dr. Bartlett. The ECLS lab uses sheep, for example, since they clot very easily.
The rules broken: University of Michigan
Despite the regulations created to uphold ethical guidelines of animal testing, the University of Michigan has recently been under fire from animal rights organizations regarding their infractions of such regulations. The People for the Ethical Treatment of Animals (PETA) sent a letter on February 6, 2023, to President Ono requesting him to take responsibility for such infractions. The letter stated that between March 2018 and June 2022, U-M “reported more than 18 violations of federal animal welfare guidelines in its laboratories to the National Institutes of Health’s (NIH) Office of Laboratory Animal Welfare, affecting nearly 12,000 animals.”
Some of these violations include 53 mice dying of dehydration due to staff carelessness, 11,548 zebrafish dying due to bleach being siphoned into tanks, and 17 live mice being put for disposal after incorrect euthanasia. All of these incidents failed to comply with the experimental methods outlined in the IACUC, thus demonstrating a flaw within the Animal Care and Use program designated to protect research animals.
U-M’s policy on non-compliance
Going forward, the University of Michigan is working toward bettering animal protocols and addressing any violations seen in animal testing. The IACUC takes reports of noncompliance with protocols seriously and may start an investigation according to U-M’s Policy on Investigating Noncompliance and Animal Welfare Concerns. Any reports will be sent to the ACUO for a preliminary assessment of the allegation. If credible, the ACUO may launch an investigation. If it is deemed that there was a serious noncompliance, the committee will determine proper corrective actions to be taken. For example, a combination of formal notices, training, and possibly punitive measures are implemented. Actions are based on the significance of the violation and the number of past violations are taken into account.
While it is too soon to tell if these new protocols will help ensure compliance with the Animal Care and Use program guidelines, it demonstrates U-M’s dedication to ethical animal testing. Only time will tell if this dedication translates to action.
Feature photo: Experimental Immunology Branch pipetting DNA samples into a tube, by National Cancer Institute on Unsplash