The need for non-human primates in biomedical research, production and testing of products and devices (update 2017)
Non-human primates are used in medical research because of their similarities to human beings. Results from research on non-human primates can often be applied to humans, and scientists have learned much about diseases, disorders, prevention and treatments for both humans and animals. Using animals that are so similar to humans, however, raises serious ethical concerns, which is why the use of non-human primates is monitored and strictly regulated. Animal testing for cosmetics was entirely banned in the European Union in March of 2013, and much also has been done to specifically safeguard non-human primates: non-human primates used for research, for example, can no longer be obtained from the wild unless the objectives of the study specifically requires the use of wild-caught; and the use of great apes has been prohibited. As long as non-human primates continue to be used for medical research, the European Commission strongly advocates the "3Rs principle", now a legal obligation embedded in the EU legislation to: Replace non-human primates with viable alternatives whenever feasible, Reduce the use of non-human primates and Refine scientific procedures and the care and treatment of the animals. This Opinion is an update of the 2009 Opinion and addresses issues specifically related to implementing the "3Rs principle".
- 1. Introduction
- 2. Background
- 3. Current use of non-human primates
- 4. Alternatives to the use of non-human primates
- 5. Reducing and refining the use of non-human primates
- 6. Determining a timeline for phasing out the use of non-human primates
- 7. Implications of an EU-ban on the use of non-human primates
- 8. Research areas to explore to further the 3R principle
- 9. Conclusion and Recommendations
4. ALTERNATIVES TO THE USE OF NON-HUMAN PRIMATES
4.1. What are the alternatives to the use of non-human primates in research and safety testing?
An increasing number of opportunities to avoid non-human primates use have been identified where they are not the relevant species, where alternative species are available and where other methods can be used. The scientific community agrees that one model can never suffice for all aspects of human diseases, so a variety of models, animals and non-animal, should be used. If one-to-one replacement of a test is not achievable, an integrated testing strategy and clinical research can be combined in a weight-of-evidence approach. Recent developments in biomedical research will potentially improve the selection of the most promising candidates for new therapies before further assessment in vivo.
Examples of currently available possibilities for replacement are:
- Case-by-case approach for the choice of a second non-rodent species and greater emphasis in regulatory guidelines on the use of alternative methods in the safety assessment of pharmaceuticals.
- Replacement strategies for treatment and prevention of infectious diseases with the development and implementation of controlled human challenge models for typhoid, Plasmodium falciparum malaria and transmission studies with specific influenza strains.
- The potential to use functional MRI studies in humans to replace some cognitive neuroscience experiments performed in non-human primates.
- Non-human primates are no longer considered acceptable organ donors for practical and ethical reasons.
4.2. Alternatives to the use of non-human primates in pharmaceutical testing and in infectious diseases, human brain and human eye research
The testing of new pharmaceuticals on non-human primates is a very small but almost compulsory part of the global testing procedure. The reason is that non-human primates are usually the species that match humans more closely in terms of how drugs affect them and tests on other species are not adequate. Drugs involving the immune system can often only be tested on non-human primates. Some alternatives are being considered, although they are currently regarded as supplying supportive data rather than being a means to replace the use of non-human primates. These alternatives include using genetically modified rodents, micro-dosing, and using a combination of techniques like testing cells in the laboratory, computer modelling and innovative tools in molecular biology, that reduce the need for animal experimentation.
Regarding infectious disease and the field of vaccine research, great strides have been made that help to reduce and replace the use of non-human primates. These include the development of –omics technologies such as genomics and proteomics, and new cell culture techniques and the development of organoïds, rapidly developing imaging techniques and telemetry infectious disease research. Human challenge models and the development of humanised mice and non-mammal animal models are other developments and a major advance has been the full replacement of non-human primates for testing of the neurovirulence of polio vaccines.
In brain research, the brain is routinely studied using non-invasive techniques that provide images of the brain’s structure and activity and detect abnormalities:
- Magnetic resonance imaging (MRI), which uses powerful magnets and radio waves to construct pictures of the internal structures of the brain, and
- Electroencephalography (EEG), which records the electrical impulses in the brain from electrodes placed on the scalp.
Recently, a new type of MRI has been developed that measures blood flow and levels of oxygen in the brain, and gives an indirect measure of brain activity, but they only measure how the brain works on a large scale and are not quick enough to respond to the way in which individual brain cells process information. Therefore, they cannot replace studies made by placing small electrodes in the brain.
New non-invasive techniques based on MRI have been developed and may greatly help to study how different nerve cells are connected both in healthy and in diseased brains. Although promising, these techniques still need to be developed further and have to be validated. Computer modelling is rapidly improving but even the best attempts cannot simulate a functioning brain, partly because we still know little about the structure of the brain itself.
Non-human primates are still being used to study the development of eye diseases and new gene therapy strategies are being tested in non-human primates before they can be applied to humans. However, progress is being made developing suitable tests that take place outside of the body (in vitro) for retinal defects for screening and for testing the efficacy of new therapies, which could be viable alternatives to testing on non-human primates. Also promising as a replacement to non-human primates testing is the use of human stem cells in developing human cell-based models, particularly for studying the retina, and models of macular degeneration.