Alternatives to animal research

The 3Rs: Their definition, application and importance to your work

Overview of the 3Rs

The 3Rs. Their definition, application and importance to your work from NC3Rs on Vimeo.

Animal Alternatives

In pursuing animal replacement alternatives, the following methods have been proposed:

• Systematic reviews
• Mathematical & computer models, informatics
• Cell culture - human ex vivo methods
• "Lower" organisms (e.g. yeast)

Systematic reviews

The National Health and Medical Research Council states in Best Practice Methodology in the Use of Animals for Scientific Purposes that “systematic review of animal-based studies should be considered where appropriate" to replace the use of animals.

Systematic reviews may also complement current animal based projects and help minimise unnecessary duplication of studies.

• The CAMARADES Systematic Review Facility is a free-to-use online platform for researchers to perform systematic review and meta-analysis of animal studies. They also provide information about systematic reviews on their website.
• You can register systematic reviews of animal research related to human health on PROSPERO. Registration of systematic reviews facilitates open science and prevents duplication of work. (Guidance document)
• If you are aiming to collate data from a systematic review using meta-analysis, then the ANU Statistical Support Network (SSN) can assist with planning and designing your review. The SSN can also provide advice on narrative reviews, which may help you find more information on a particular topic. Information on other statistical support can be found here.
• If a systematic review of a specific research question may be a suitable alternative for your project, there are a number of ANU contacts who are available to assist further with your project plans – see the Questions? section.

Non-animal modelling

It may be worthwhile investigating the suitability of these non-animal based alternatives for future work.

In silico

Computer models can simulate human biology, progression of diseases, and predict how likely a substance is to be hazardous. Although modelling may not be able to replace research into complex reactions and processes in whole-body systems, it is worth exploring for use in preliminary work as proof of concept or development of new techniques.

• Quantitative structure-activity relationships (QSARs) are computer-based techniques which estimate the likelihood a substance is hazardous, based on its similarity to existing substances and our knowledge of human biology.
  • QSAR toolbox is a free software application that can be used for this.
  • QSAR4U lists additional tools and approaches in this area.
• Cyprotex offers a range of prediction tools for researchers.

In vitro

• Human cells ex vivo
  • Mini-brain – functional models of the human brain created using induced pluripotent stem cells (iPSCs). See also journal article.
  • Human organs-on-chips – human cells grown on chips to mimic the function of organs and organ systems. See also media article.
  • Nerve-on-a-chip – human cells are grown on a chip to mimic nerve tissue form and function.
• Microorganisms and non-vertebrates (e.g. yeast Saccharomyces cerevisiae, fruit fly Drosophila melanogaster, roundworm Caenorhabditis elegans)

Questions?

Contacts

• For advice on the 3Rs and alternative strategies to reduce or replace animals in research projects, testing and teaching, contact Dr Brett Lidbury (Associate Professor and Alternatives Advisor to ANU Animal Ethics Committee) at brett.lidbury@anu.edu.au or phone on 6125 7875.
• Any questions about animal research - ANU Vet Services Team (vetservices.rsd@anu.edu.au)
• Systematic reviews - Professor David Nisbet (david.nisbet@anu.edu.au)
• Biological Data Science Unit (BDSI), ANU College of Science also provides consultancy and courses including statistical data modelling and analysis for biological research projects. Further information on BDSI can be found on: Biological Data Science Institute | The Australian National University (anu.edu.au)

International links and collaborators

• CAAT Europe (University of Konstanz, Germany)
• Swedish Fund for Research Without Animal Experiments

Resources to support alternatives research

There are a number of great online resources available. The ANU Vet Services Team can assist you further if you have a specific interest.

• NC3Rs (UK) - Plenty of excellent resources and information available via this site. Go to the "Our Resources" link at the top of the NC3Rs home page for guidance on experimental design, sampling, ARRIVE and more.
• Canadian Council on Animal Care online training modules
• ANZCCART – Aus/New Zealand Council for the Care of Animals in Research and Teaching
• PREPARE - Guidelines and checklist for planning animal research and testing (UK, endorsed by ANZCCART)
• ARRIVE - Guidelines and checklist for the reporting of research using animals in publications (UK, endorsed by ANZCCART)

Useful publications

These publications contribute to the debate on whether the use of animals as research models in the biomedical field are valuable and justified.

• ALTBIB – bibliography of animal alternatives literature, via the National Library of Medicine (United States)
• ALTEX - International journal of "Alternatives to Animal Experimentation" (2018 Impact Factor = 6.183)
• ATLA – International journal of "Alternatives to Laboratory Animals" (United Kingdom)
• Leist et al. (2012) provide a review of alternatives to animals for testing and research.
• Human studies (from: Balls M. (1994). Laboratory Animals, 28:193-211)