The alternatives to animal testing
Animal models are used to study the effects of drugs and chemicals before testing them on human volunteers. Every year, millions of experimental animals are used all over the world for the advancement of research and development in medical technology. The suffering experienced by the animals during these experiments is a debated issue. Besides the ethical concern, lack of skilled manpower, time-consuming protocols, and high maintenance costs are other drawbacks of animal-based experiments. Different methods and alternatives are, thus, required to minimize the use of animals in scientific experiments.
1. The three R’s: Reduction, Refinement, and Replacement:
The three Rs principle was coined in 1959 by two English biologists, Russel and Burch in their book “The principle of humane experimental technique”. The concept motivates researchers to reduce the use of the total number of animals in an experiment, refine the protocols to minimize the pain caused to them, and find alternatives to replace the use of conscious living vertebrates in animal experimentation (1).
2. The use of organ-on-chip and cell cultures:
Organs-on-chips (OoCs) are three-dimensional engineered systems that can reliably mimic human physiology thereby enabling to avoid the use of animal models. For instance, the multichannel microfluidic system allows tissue perfusion acting as engineered vessels for nutrient exchange. Thanks to dramatic advancements in bioengineering, working OoC models are nowadays available for the kidney, lung, skin, liver, and even the female reproductive system.
These models allow to bridge the gap between animal and human systems in the context of disease research, toxicity, and drug testing (2). In vitro cell and tissue cultures as well as three-dimensional organoids are important alternatives for animal experiments. They allow growing cells outside the body in the laboratory in a suitable growth medium and supplements. Cell cultures are easy to follow, cost-effective, and less time-consuming as compared to animal models. Organ and tissue cultures can be used to evaluate the toxic effects of a chemical in vitro (3).
3. Computer (in Silico) modeling
Computer simulation models are faster, more effective, and cheaper than animal experiments. They will soon play a crucial role in the early stages of drug development. In 2017, researchers from the University of Oxford (UK) successfully developed computer simulations that outperformed animal models in predicting the clinical risk of drug-induced arrhythmias. However, there is a limit to what computer simulations can do for us and ever-evolving mathematical knowledge and understanding are required to improve the computer models to entirely replace animal experiments (4).
1. Curzer HJ, Perry G, Wallace MC, Perry D. The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why. Sci Eng Ethics. 2016 Apr;22(2):549-65. doi: 10.1007/s11948-015-9659-8. Epub 2015 May 31. PMID: 26026966.
2. Wu Q, Liu J, Wang X, Feng L, Wu J, Zhu X, Wen W, Gong X. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online. 2020 Feb 12;19(1):9. doi: 10.1186/s12938-020-0752-0. PMID: 32050989; PMCID: PMC7017614.
3. Xu KP, Li XF, Yu FS. Corneal organ culture model for assessing epithelial responses to surfactants. Toxicol Sci. 2000 Dec;58(2):306-14. doi: 10.1093/toxsci/58.2.306. PMID: 11099643.
4. Passini E, Britton OJ, Lu HR, Rohrbacher J, Hermans AN, Gallacher DJ, Greig RJH, Bueno-Orovio A, Rodriguez B. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity. Front Physiol. 2017 Sep 12;8:668. doi: 10.3389/fphys.2017.00668. PMID: 28955244; PMCID: PMC5601077.