Eliminating Animal Products from Life Science Research

It has been over 60 years since Russell and Burch first conceptualized the “3Rs” in their book, The Principles of Humane Experimental Technique. Intended as a framework for Replacing, Reducing, and Refining the use of animals in research, the 3Rs now form the basis for countless regulatory systems governing animal welfare, and are used by institutions worldwide to help guide the transition to animal-free lab work. Some of the animal-free approaches being developed for life science research are discussed below, including challenges to their adoption. 

Animals and animal-derived products have long been used to identify the causes of various diseases and develop effective treatments. However, utilizing animals in this way raises a number of issues, not least ethical considerations. Many animals are sentient beings, capable of experiencing pain and suffering, and there is growing opposition to their use in research, both among scientists and the general public. 

The use of animals and animal-derived products also presents several scientific concerns. First, the extrapolation of data from animals to humans can only go so far due to phylogenetic differences. Second, products of animal origin often have immunogenic potential and can demonstrate inherent biological variability. Additionally, for certain animal-derived products, there is the risk that supply may run out—polyclonal antibodies being a prime example. 

Lastly, the use of animals in research comes with an array of regulatory requirements, which differ between countries. These include Directive 2010/63/EU, which regulates animal research in the European Union; the Animal Welfare Act, a US Federal Law that covers the use of animals in research; and the FDA Modernization Act 2.0, a bill passed in 2022 that authorizes alternatives to animal testing and removes animal studies for biosimilar products. 

To address these issues and better align with the 3Rs, many scientists are switching to animal-free products and practices for their research. Some of the available options are discussed below, focusing mainly on in vitro applications. 

Of the many different animal-derived products used in in vitro research, fetal bovine serum (FBS), extracellular matrix proteins such as Matrigel™, and antibodies are among the most common. It is estimated that more than 2 million bovine fetuses are sacrificed annually for FBS extraction, a practice that not only causes fetal suffering but also generates an undefined product that can influence experimental reproducibility. Alternatives to FBS that are being investigated include bovine ocular fluid (a by-product of the meat industry), sericin (a glue protein derived from raw silk), and various chemically defined xeno-free media. 

Matrigel, a basement membrane harvested from the Engelbreth-Holm-Swarm mouse sarcoma, is the most widely used material to mimic the ECM. However, because its production involves killing vast numbers of mice per year, as well as results in batch-to-batch variations, there is growing interest in using synthetic peptide hydrogels. Examples include BioGelx™, PeptiGels®, and VitroGel®, which have been literature-cited for 3D culture of primary human hepatocytes, respiratory epithelial cells, and pancreatic cancer, among many other applications. 

Traditional polyclonal and monoclonal antibodies are produced by immunizing animals, most often rabbits and mice, and either extracting the immunoglobulins from the serum (polyclonals) or generating hybridoma (monoclonals). However, the well-documented reproducibility crisis combined with the 3Rs principles has seen the use of recombinant antibodies becoming more widespread. Methods for recombinant antibody production include display technologies (e.g., antibody phage display), sequencing of existing clones for expression in a mammalian cell line, and more recently, machine learning. 

Other areas being explored in the drive toward animal-free research include organoids, the complex mini-organs derived from human stem cells that allow for mimicking physiological systems, and organ-on-a-chip technology, which can replicate the structure and function of human organs under dynamic conditions. In addition, in silico approaches such as QASR Toolbox and VirtualToxLab are being used in drug discovery and toxicology, respectively, to predict key aspects of synthetic and natural compounds. 

One of the major challenges to achieve animal-free research lies in convincing scientists to adopt new ways of working. Often, time constraints can mean that evaluating and optimizing alternative methods simply isn’t feasible. Overcoming ingrained biases and institutional practices presents a further hurdle. Cost is another factor, with newer products often having a higher price-tag than established options. Despite this, the global scientific community is decisively moving away from animal-use, aided by scientific advancements and supportive regulatory frameworks in the EU and US. 

LubioScience represents some of the most trusted brands in life science research and works closely with partners including Amsbio, Cytion, BPS Bioscience, and Pacific Coast Biologics to help smooth the transition to animal-free lab work. Our product portfolio includes StemFit® chemically defined culture media, iMatrix laminin fragments, and CELLBANKER Freezing Media, which can be used together for stem cell culture. Contact us today to discuss how we can support your project. 

Duarte AC, Costa EC, Filipe HAL, et al. Animal-derived products in science and current alternatives. Biomater Adv. 2023;151:213428. doi:10.1016/j.bioadv.2023.213428 

Kiani AK, Pheby D, Henehan G, et al. Ethical considerations regarding animal experimentation. J Prev Med Hyg. 2022;63(2 Suppl 3):E255-E266. Published 2022 Oct 17. doi:10.15167/2421-4248/jpmh2022.63.2S3.2768