Biomedical research using animals is essential to the understanding of the complex biological processes that govern life and underlie the development and control of diseases. The use of different animal models ranging from rather simple invertebrates to non-human primates remains key to much medical progress. In July this year, the Basel Declaration Society hosted a conference in London to discuss increasing transparency in animal research with topics ranging from honest communication and education about research using animals to the need for unified guidelines to facilitate robust experimental design, analysis and reporting of animal studies. Biome caught up with Rolf Zeller, President of the Basel Declaration Society, to learn more about the society and what it aims to achieve.
How did the Basel Declaration come into being?
The Basel Declaration originated as the result of about 80 scientists from different European countries meeting in Basel, Switzerland, in November 2010 to discuss how to improve the general understanding and public perception of the need for research involving animals. At that time, we were aware that a new European Union directive governing animal research was being drafted without significant involvement from the scientific community at large. Events in Switzerland, and several other European countries, made scientists realise the need to be proactive rather than reactive concerning issues involving research using animals. In particular, there was an urgent need for more openness and permanent dialogue among the different stakeholders, i.e. researchers, animal welfare officers, Editors, and of course the general public.
What is the aim of the Basel Declaration?
The Basel Declaration was adopted in November 2010 as an explicit call for more trust, transparency and open communication concerning academic research with animals. Since then, over 2400 scientists from all over the world have signed the Basel Declaration and committed themselves to research with animals that respects the highest ethical standards. The cornerstones of the Basel Declaration include a commitment to the best care of animals and strict adherence to the 3R principles: of replacement, reduction and refinement when using animals in scientific experiments. (see more below).
In addition, the Basel Declaration supports improved education and training of all people using animals for research and open and transparent communication. Signatories of the Basel Declaration acknowledge that animal research is essential for medical progress and that basic and applied research are inseparably linked. The Basel Declaration Society (BDS) was formally founded in 2011 to provide a ‘home’ for the Declaration and to bring its principles to fruition through different activities. For example, the annual Basel Declaration Award aims to improve the technical knowledge and practical skills of people involved in animal experimentation. A second major task of the BDS is to organize conferences such as the recent London conference on ‘Transparency in animal research: Implementing openness in publication and communication’ which had over 100 participants from across the world.
Scientists, animal welfare officers and Editors often refer to the ‘3R principles’ when using animals in research. Can you elaborate on their importance?
The 3R principles that stand for replacement, reduction and refinement were formulated by Russell and Birch in 1959 in their book titled ‘The principles of humane experimentation’. ‘Replacement’ refers to methods that avoid or replace the use of animals (e.g. use of cell lines, computer models or human volunteers). ‘Reduction’ refers to the use of fewer animals where possible (e.g. by improvement in the statistical design of experiments). ‘Refinement’ refers to improvements to the care of animals which minimise any possible pain or distress when the use of animals is unavoidable.
Nowadays, the 3Rs have become an integral part of most national laws and the European Directive governing animal research in Europe. The practical implementation of the 3Rs means that studies must be designed such that experiments involving animals are only done when no valid alternative exists and they should use the minimal number of animals to obtain reproducible and statistically relevant results. Furthermore, the most appropriate methodology and analysis must be used and efforts made to keep any possible distress and suffering of animals to a minimum.
It is important to realize that the 3R principles do not implicitly aim to replace all experiments using animals, but to minimize their number where possible. Good research groups combine animal studies with cellular and increasingly more in silico approaches. In fact, a central tenet of systems biology is to combine quantitative biology in animal and cellular models with in silico approaches, which is fully in line with the 3R principles. Finally, animal studies are always rather expensive, which provides an additional incentive to minimize the number of animal experiments. Again, I think researchers need to be open about all these issues and let the general public know how they have implemented the 3Rs in their research.
Since 1964 research involving people should comply with the ‘Declaration of Helsinki’. Why has it taken so long for something similar to come about for research involving animals?
Scientists in general like to focus on their research and rarely communicate with the general public with the exception of major scientific breakthroughs. In spite of the fact that the 3R principles were conceived in 1959 and progressively implemented in the laws, rules and regulations governing animal research in different countries, it took scientists a long time to realize that it is important that they take a clear stand on the issues concerning animal experimentation. Rather than being pressed by lawmakers and animal welfare organizations, scientists have to be at the forefront too. The scientific community at large is becoming more aware of their responsibility toward the general public and the number of scientists willing to endorse ethically responsible animal research and engage in an open dialog concerning these issues is increasing. I hope that for the students and postdoctoral fellows that we are training today, this responsibility and permanent dialog with society will simply be a natural part of their ‘daily routine’. It is important to make the general public aware of the fact that we have nothing to hide and that research will actually benefit from using the highest standards for the treatment of animals as put forward in the Basel Declaration.
How can scientists promote public understanding of the importance of animal models in research?
It is very simple – by being totally transparent about research involving animals. It is still not uncommon that press releases concerning major scientific discoveries downplay or even fail to mention the essential role of animal models in achieving the progress. In addition, there is a second major problem: once development of a drug or clinical procedure enters clinical trials in humans and final approval, the often decades of basic and applied research using different animal models are simply ‘forgotten’. Imagine the opposite scenario that openly acknowledges the role that animals played. For example, on each drug or surgical device etc there could be a caption saying “this drug/device was developed and tested using animals for your health and safety”.
Short of that, all scientists must be completely open and frank about the importance of research with animals for basic and applied biomedical research progress and combat the erroneous allegations that animal research has not cured one patient by making appropriate counterarguments. For example, at the recent conference it was noted that scientists in the UK that are engaged in open communication about the importance and contribution of animal research to medical progress have not become the targets of extremists, which is still most often used as an argument against openness.
What should journals be doing to promote transparency in animal research?
I think scientific journals should endorse and enforce guidelines such as the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, which are intended to improve the reporting of animal experiments. I consider it important that we, as researchers and peer reviewers, work together with editors and publishers to have a set of one – not many – universally implemented guidelines governing the publication of animal research. Peer reviewers must be asked to specifically comment on the parts of the studies involving animals with respect to the 3R principles of replacement, reduction and refinement and the methods used. The journals should work together with the relevant organizations and funding bodies to provide open access, curated and searchable databases that make available all primary and ‘so-called’ negative data generated from a particular study. This should be implemented in a manner similar to what is now standard for genome and omics data sets. Journals should also make the readers aware of these databases and the importance of full disclosure of all animal experiments. The only exceptions might be cases where full disclosure might infringe on patenting/licensing. These issues were also discussed in detail at the recent London conference and the relevant position papers can be downloaded here.
What are the main challenges facing the Basel Declaration Society today?
I think there was a sense at the London conference that the Basel Declaration and its Society have made a big step toward becoming a truly global organization. The BDS must network with the relevant national organizations to work toward rallying more scientists to join and help the worldwide implementation of the aims of the Basel Declaration. Open dialogue about experiments involving animals must become permanent and not limited to periods when animal research and/or scientists are specifically threatened – this is a very long process. The BDS is an independent grass-root organization for academic research and animal welfare scientists, but it is important to interact with other relevant bodies such as the pharmaceutical industry to generate synergies. The BDS needs to raise more funds from individual and institutional members and donations, so that future conferences can be organized. The London conference was unique in bringing together different stakeholders from academia, granting agencies, journals, pharmaceutical organizations, lawmakers and animal welfare organizations for two days of intense and fruitful discussions. These conferences are important to further the broad implementation of the Basel Declaration into daily research practice, which deserves more support in my opinion!