Do we still need animals in the lab?

The pharmaceutical and biotechnology industries are heavily regulated. Governmental organisations such as the Medicines and Health Regulatory Authority (MHRA) in the UK, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in the US impose rules on the drug development process. Moving a drug through the development pipeline at present requires preclinical studies and toxicology studies to be completed. Some of these studies currently require the use of animals to determine whether a drug is safe and what dosing regimen may be appropriate (1).

Naturally, many people find the idea of testing animals for drug discovery unethical and would prefer the industry to move away from this model. Interestingly, many research groups have been looking at alternatives to animal models. This concern has been the topic of debate as early as 1992 when the need for three R’s in research was discussed. These were Replacement, Reduction, and Refinement (2).

With technology advancing rapidly and new systems and models becoming more applicable, we are in a position to consider the need for animals in the lab. One of the significant advances that may be interesting is the use of stem cells.

Stem cells may provide an exciting alternative to animals as in vitro (or in the petri dish) models of disease and for toxicological examination. Genes associated with disease genes can be inserted into stem cells via several methods. These cells can then be induced to differentiate into human disease tissues, which can be used to screen for drugs. These miniature versions of human tissue are superior to Petri dishes of a single cell type to assess the toxicological impact of a drug. They provide a human impact profile which is more relevant to the profile obtained from a mouse (3).

Diabetes and Alzheimer’s disease are linked with a mix of genetic and environmental roots. Researchers have now used stem cells to screen new drugs for the treatment of these common diseases (4).

Biotechnology companies can use stem cells to test potential drug candidates for toxicity. This could help companies avoid wasting time on harmful composites that may not be applicable to humans at all. Stem cell screens could form a critical factor in the prioritisation of compounds early in the discovery and development process (4).

Another exciting avenue revolves around the combination of technology, mathematics and biology, as researchers develop organ-on-chip systems and body-on-chip systems to test compounds and model physiological interactions within the body. The possibility of reproducing interactions between organs by connecting different organ modules is fascinating and could significantly affect the feasibility of drugs within the clinical trial pipeline. Recently, researchers have designed a three‐organ system consisting of pancreas, muscle, and liver. These systems have allowed them to illustrate glucose metabolism and homeostasis by constructing a mathematical model of glucose metabolism, based on experimental measurement of glucose uptake by muscle cells and insulin secretion by pancreas cells. Similar systems could be used to determine the feasibility of a candidate drug more fully than animal models currently deliver (5). 

We may not be able to fully move away from animal models at this stage, as research into alternatives is in its early stages. However, we can, where feasible, consider suitable options in the initial stages of research. With current regulations, no new drug can be used in patients until it has been extensively tested. Part of this testing will likely need to be done in animals for the foreseeable future. However, it is our responsibility as scientists to develop alternative methods which will allow us to reduce the number of animals required for drug research.