The use of animal models in pharmaceutical trials is inhumane, ineffective, and expensive. So why are viable alternatives having such a difficult time breaking into the industry?
The use of animal models in research presents intense ethical dilemmas; can exploitative means ever be justified by their ends? Is the suffering of thousands of one species justified if it ultimately relieves the suffering of millions of another? Instead of engaging with this impossible moral dilemma some brilliant researchers have developed a potential solution to completely replace the need for animals in research: organ chips.
Traditional petri dish style cell cultures lack many qualities necessary for pharmaceutical testing. Cells grown in a flat layer on a plate have their physical qualities altered compared to cells living inside the environment of an animal. This makes the cell’s reaction to substances less accurate compared to how they would react inside living bodies. Growing cells in simple multi-layered cultures helps resolve some of these issues; however, these cultures have other limitations, such as being difficult to photograph during research. Organ chips resolve most of the major issues plaguing traditional cell cultures by culturing cells on complex three-dimensional structures within the chips, allowing fluid to more naturally flow through the chip rather than sitting stagnant and composing the chips with clear materials in order to allow for high resolution imaging.
Organ chips have been developed through interdisciplinary work in cell biology, engineering, and material science to simulate living tissues and organs. Each organ chip is specifically developed for the particular body environment it is emulating. This includes how the chip is structured, which cells are used, the speed at which fluid flows through the chip, and simulated mechanical stressors (such as emulated breathing). Organ chips have replicated the brain, blood vessels, cartilage, eyes, fat tissue, the heart, the immune system, the small intestine, the liver, the lung, skin, teeth and more. Different organ chips can even be lined up to replicate entire organ systems!
Pharmaceutical trials currently legally mandate that animal subjects be used for safety and efficacy testing of drugs because the use of traditional cell cultures alone can not provide enough information on a substance before beginning human trials. However, organ chips have already shown great promise in being, not only equivalent to animal models, but superior. Animal models frequently fail to predict therapeutic responses in humans resulting in drugs passing the animal testing phase only to be ineffective or even dangerous for humans. Furthermore, it is highly likely drugs that are safe and effective for humans have been missed because of ineffective responses in non-human species. In individual studies organ chips have proven to give superior predictive results to animal models. Organ chips also show great promise in precision medicine. A particular patient’s cells can be lined on an organ chip to predict how an individual’s unique body will react to a particular medicine.
Organ chips have several barriers currently preventing them from replacing animal models. First, the material polydimethylsiloxane frequently used in organ chips can also absorb certain drugs like sex steroids, limiting the effectiveness of organ chips in certain studies. Second, organ chips also currently have lower viability in early phases of drug research because these phases require models with higher throughput to quickly screen candidates. However, this particular barrier may be overcome by automating screening. Finally, each specific organ chip will likely require approval for each specific study use, replacing animal models in one niche area at a time.
Sadly, the number of animals used in research in Canada remains high. In 2022, over 3.5 million animals were used in research studies in Canadian Council of Animal Care (CCAC) certified labs. It is important to note that this number fails to capture many private labs who choose not to report their statistics.
The largest challenge in replacing animal models with organ chips is the resistance from pharmaceutical, regulatory and academic researchers who have invested a lot of money in animal model-based research. Millions have been spent on developing special lines of lab animals and constructing complex regulatory frameworks based on animal model benchmarks. Legal regulation walls are frequently developed one brick at a time, with new regulations building on previous ones. It is much more challenging to knock down an entire framework to rework systems from the ground up.
There are indicators that change is coming. The number of animals used in CACC certified labs decreased by over 150,000 between 2021 and 2022. In 2020, the global organ chip market size was approximately USD 41 million and is expected to reach USD 303.6 million by 2026. The technology is here, but it will require pressure on legislators to change current regulations and pressure on pharmaceutical companies to invest in implementing the new technology to finally remove live animals from research.
If you enjoyed this article, consider reaching out to U of T Law’s Animal Justice Club at ajstudents6@gmail.com to join our events email list or to inquire about more ways to get involved in the conversation and fight for animal rights.
Editor’s Note: Olivia Schenk (3L) is a member of the Animal Justice Club
Editor’s Note: Additional sources used throughout re organ chip technology and industry challenges
Source 1: Ingber, D.E. Human organs-on-chips for disease modeling, drug development and personalized medicine. (2022). Nat Rev Genet, 23, 467–491. https://doi.org/10.1038/s41576-022-00466-9/
Source 2: Singh, D., Mathur, A., Arora, S., Roy, S., & Mahindroo, N. (2022). Journey of organ on a chip technology and its role in future healthcare scenario. Appl Surf Sci Adv, 9, 100246. https://doi.org/10.1016/j.apsadv.2022.100246.