The Use of Animal Testing in Medical Research

Animal testing has always played a crucial role in biomedical research and in Drug Discovery and Development, providing important insights that have led to significant medical advancements. Despite the controversies surrounding its ethical implications, animal testing remains the groundwork of every life sciences investigation practice due to the exceptional insights it provides. 

This blog explores why is animal testing still necessary in biomedical research, delving into reasons for animal testing questionable nature. We will also examine the ethical pathways being pursued to move beyond traditional animal experiments, focusing on the promising role of Zebrafish.

Understanding Why Animal Testing Remains Essential

Is animal testing necessary? The answer to this question lies in the multiple motives why animal testing is necessary for the advancement of medical research, as well as in the regulatory aspects that support its role in safety assessment.

One of the primary reasons for animal testing is the biological similarities between animal models and humans. Many animals, especially mammals, share a significant portion of their genetic makeup with humans. For instance, mice share approximately 98% of their genes with humans. This genetic similarity makes them more suitable models for studying human diseases and potential treatments. 

Another reason why animal testing is necessary is the complexity of human diseases, especially conditions such as cancer, cardiovascular diseases, and neurological disorders. Studying these diseases in animal models provides a whole-organism context, essential for exploring the interactions between different tissues and systems within the organism. This holistic approach is critical because many diseases affect more than one organ and have systemic implications. 

Safety testing is another critical aspect beyond the reasons for animal testing. Regulatory agencies worldwide mandate animal testing to guarantee the safety and efficacy of new products before they are placed on the market. These agencies have established stringent guidelines and protocols before a drug can progress from the pre-clinical phase to Clinical Trials. This is a fundamental reason why animal testing is necessary. The process helps identify potential toxic effects and adverse reactions, ensuring that novel drugs in a certain dosage are safe for human use. Without this critical step, the risk of unpredicted side effects in humans would be significantly higher.

Moreover, animal testing provides a reliable platform for studying the long-term effects of treatments for chronic diseases. Chronic conditions often require prolonged observation to understand their progression and response to therapies. Animal testing is necessary to comply with regulatory requirements of a thorough evaluation of a drug’s carcinogenic potential, cardiotoxicity, reproductive toxicity, or developmental toxicity, for example. These long-term studies would be impractical or unethical to conduct in humans. 

Research Ethics: Pathways Beyond Animal Experiments 

Despite the undeniable contributions of animal testing to medical research, it is important to continue exploring and developing ethical alternatives. Especially in the chemical and medical fields, there has grown a strong tendency in the last decade to develop and implement alternatives that complement or reduce traditional animal models. The ethical considerations surrounding animal testing have, thus, led to significant advancements in research methodologies aimed at reducing the reliance on traditional animal models. 

These efforts are guided by the "3Rs" principle: Replacement, Reduction, and Refinement. Animal testing replacement focuses on finding new alternative methods (NAMs) that do not involve experimental animals. At the same time, the reduction principle aims to minimize the number of animals used in research by optimizing experimental design and statistical power analysis. Refine animal testing involves adapting experimental procedures to minimize pain, suffering, and distress, enhancing animals' welfare. In Drug Discovery and Development, the Zebrafish alternative model has been used especially in toxicology and safety preclinical assays, as they provide a powerful alternative to traditional mammalian models, and their use perfectly aligns with the 3Rs principle.

 The European Union Directive 2010/63/EU  from 2010 declared that early life-stage animals are not considered experimental animals until they begin feeding independently after leaving the chorion. Zebrafish embryos under 5-6 days post-fertilization (dpf) fall into this category. As a result, these embryos are not classified as experimental animal models but rather as New Alternative Models (NAMs) from a regulatory and legislative standpoint. This characteristic aligns with modern guidelines that advocate for replacing traditional animal models. At the same time, they combine all the advantages of both in vitro and in vivo models in one reliable NAM.

Their high fecundity allows for conducting large-scale studies with a relatively small number of breeding adults. A single pair of Zebrafish can produce hundreds of embryos per week, facilitating extensive compound screening and genetic research. This high reproductive rate, combined with their small size, simplifies performing multiple experiments simultaneously, significantly reducing the overall number of animals required. Additionally, as Zebrafish are highly suitable for advanced automated imaging and data analysis technologies, like High-Content Screenings (HCS), they allow for generating more robust and reproducible data using fewer animals.

Moreover, Zebrafish maintenance and breeding are relatively straightforward and can be performed under conditions that minimize stress. The transparent nature of their embryos allows for non-invasive imaging techniques, reducing the need for more hostile procedures that can cause pain or distress. For example, organ development and disease progression can be monitored in living zebrafish embryos by image analysis without requiring more complex procedures such as surgical interventions. 

In conclusion, while animal testing is still necessary for certain aspects of medical research, the scientific community continually seeks ethical alternatives that can reduce the use of traditional animal models. The use of Zebrafish exemplifies the innovative alternative approaches being developed to complement or replace traditional animal models, offering a promising pathway toward more ethical and effective biomedical research. 

Sources

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Díaz L, Zambrano E, Flores ME, Contreras M, Crispín JC, Alemán G, et al. Ethical Considerations in Animal Research: The Principle of 3R’s. Rev Invest Clin. 2020;73(4):199-209. 

Bauer B, Mally A, Liedtke D. Zebrafish Embryos and Larvae as Alternative Animal Models for Toxicity Testing. Int J Mol Sci. 2021;22(24):13417. 

Cassar S, Adatto I, Freeman JL, Gamse JT, Iturria I, Lawrence C, et al. Use of Zebrafish in Drug Discovery Toxicology. Chem Res Toxicol. 2020;33(1):95-118.