By Ian Nandlall
The medical field has always been progressive, at least at first glance. However, it has badly underperformed in many key areas concerning sustainability. On top of an environmental impact amounting to roughly 4.4% of global net emissions, the healthcare industry engages in poor animal welfare practices. This is especially true in the context of biomedical experimentation, particularly when it comes to developing and testing drugs.
Despite the introduction of the Three Rs principle (Replacement, Reduction, and Refinement) in 1959 as a guideline for reducing animal testing, the practice is still widespread today. As such, one could argue that few medicines are truly vegan or vegetarian.
WHAT IS WRONG WITH ANIMAL TESTING?
Many non-human animals have been subjected to suffering in the name of advancing medical science. Animal testing was introduced to minimize and prevent unwanted effects during and after human clinical trials. Some researchers support the “necessity” of animal testing as it is seen as a more ethical alternative to humans. Also, many claim that animal data correlates well with human biology. In their view, animal testing would be impossible to replace.
However, several studies have exposed the poor quality of animal research and its failure to translate well to human applications. For instance, 172 drugs designed for treating Alzheimer’s disease failed in humans despite success in animal trials. Corticosteroids, drugs used to treat inflammatory diseases, cause abnormal fetal development in non-human animals but not in humans. Certain diseases and conditions such as amyotrophic lateral sclerosis (ALS) and traumatic brain injury (TBI) develop differently in animal models.
An obvious reason for these issues is that non-human animals exhibit differences in terms of basic anatomy and physiology when compared to humans. Thus, drugs are not metabolized in the same manner and the biological pathways through which diseases develop are not the same. Also, the often stressful conditions that non-human animals are subjected to during experimentation may also change their physiology and cause unpredictable effects on disease states and drug metabolism. This means that not only is animal testing irrelevant and cruel, but it causes harm to humans as well by denying them promising drugs that fail animal trials.
In some cases, humans could be subjected to dangerous substances thought to be safe due to unreliable data. Such was the case with Vioxx, an infamous anti-inflammatory drug that was taken off the market in 2004 due to its adverse effect on cardiovascular health in humans. The manufacturer’s claim that the drug was safe had mainly relied on data obtained from African green monkeys.
Some supporters of animal testing would argue that better controlled animal studies and models are all that are required to solve these issues. One possible measure is more diligent breeding. The practicality of this method is unclear. It seems unreasonable to expect that an animal subject would become an acceptable proxy for humans simply by inducing mutation after mutation, especially when methods that better reflect human biology exist.
WHAT ARE SOME OF THE ALTERNATIVES THAT CURRENTLY EXIST OR ARE IN DEVELOPMENT?
Today, there exist many alternative experimentation methods that are worthy of attention.
In vitro testing refers to experimentation on biological organisms (i.e. bacteria, fungi, viruses), cells, or molecules outside of larger organisms such as humans or non-human animals. As an example, consider atopic dermatitis, more widely known as eczema. Mice are commonly used in animal research regarding this condition, despite the fact that their skin exhibits key differences (i.e. number of layers, types of immune cells) that have an impact on how eczema develops and responds to treatment. Three-dimensional models derived from human skin and immune cells would allow researchers to examine eczema in a context that takes into account human skin properties. In the future, more refined models could include other factors that play a role in the development of eczema, such as mechanical “wear and tear” as well as blood supply.
Another method involves the use of bioplastic based devices that contain fluid channels lined with human derived cells. These devices are commonly known as “organs on chips” and are essentially slices of functional organs that can be exposed to mechanical stress and different substances, such as drugs. “Organs on chips” show incredible promise in terms of cost-effectiveness, versatility, sustainability, as well as physiological relevance and accuracy in terms of determining drug toxicity. However, the technology is still in its infancy, and their suitability remains to be seen.
There are also more specific types of in vitro testing and refers to involving the use of omics, an umbrella term for sub-disciplines such as genomics (the study of genes and their functions), proteomics (the study of proteins), and metabolomics (the study of metabolites, the byproduct of medications following metabolism). It is next to impossible to go into detail given the immense scope of omics, but the basic idea is to study the effects of medications and toxins on changes regarding gene expression, proteins, and so on. These methods serve more of a theoretical basis as opposed to practical when it comes to clinical testing, but could help in drug development and understanding disease at a fundamental level.
A third type of method encompasses in silico experimentation, which involves the use of simulation using computer-based models. Within the context of therapeutics, they mostly work to complement in vitro methods by predicting toxicity of medications. The number of in silico models that exist is large, but there are several key categories. The first involves identifying biochemical similarities between medications and their byproducts following metabolism with already known toxins. The second type involves the use of equations that predict potential toxicity of a drug based on the level of drug accumulation and the degree to which it interacts with human tissue. These are known as pharmacodynamic and pharmacokinetic models. Although promising, their use as a sole alternative to other methods is limited due to their relatively small scope and difficulty to factor in all possible variables. However, in silico experimentation will likely become an invaluable addition to other alternative methods in the future.
Lastly, attention has been drawn to early microdose drug studies in human volunteers. In this context, participants are exposed to very low doses of an experimental drug, allowing researchers to study how the medication interacts with the human organism on a basic level. However, this requires the development of extremely sensitive methods that are capable of measuring drug activity at a very small scale such as liquid chromatography (the use of chemical methods to separate parts of a mixture). Also, this technology would need to be adapted to different types of drugs and may not currently be usable for certain medications, which limits its use for now.
CONCLUSION
All of the these methods have the potential to replace animal testing as more ethical, accurate, and reliable alternatives. However, such an evolution requires not only a large amount of resources, but dramatic shifts in culture, mentality and core values. While it is unclear if these methods will evolve enough to supplant animal testing within the next century, it is an ideal that we should strive for. At the very least, there is a strong possibility that these methods will co-exist with current experimentation methods, which will hopefully lead to a significant decrease in animal experimentation as a whole.
About the Author:
Ian was a longtime vegetarian, recently turned vegan, as well as a new contributor to VegOttawa. Among his interests are animal ethics, biomedical sciences and physics, and the environmental benefits of a plant-based diet.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025138/
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