Dr. Roman Stilling
Disclaimer: The opinions, views, and claims expressed in this essay are those of the author and do not necessarily reflect any opinion whatsoever of the members of the editorial board. The editorial board further reserves the right not to be responsible for the correctness of the information provided. Liability claims regarding damage caused by the use of any information provided will therefore be rejected.
Roman Stilling graduated with a B.Sc. in Biosciences from the University of Mün-ster in 2008 and received a Ph.D. degree from the International Max Planck Re-search School for Neurosciences / University of Göttingen in 2013. Afterwards he joined the APC Microbiome Ireland in Cork, Ireland, as postdoctoral researcher. Since 2016 he is the scientific officer for for the information initiative “Tierver-suche verstehen”1, coordinated by the Alliance of Science Organisations in Germany.
Ethical concerns on using animals in biomedical research have been raised since the 19th century. For example, in England the “Cruelty to Animals Act” was passed in 1876 as a result of a debate especially on the use of dogs un-der inhumane conditions such as invasive physiological experiments or demonstrations without general anaesthe-sia. Interestingly, it was Charles Darwin who put in all his scientific and political gravitas to push for regulation by the law while at the same time providing highly differen-tiated argumentation towards using animals for advancing knowledge, especially in the quickly developing field of physiology 1,2. In an 1881 letter to a Swedish colleague he wrote:
“[. . . ]I fear that in some parts of Europe little regard is paid to the sufferings of animals, and if this be the case I should be glad to hear of legislation against inhumanity in any such country. On the other hand, I know that physiology cannot possibly progress except by means of experiments on living animals, and I feel the deepest conviction that he
who retards the progress of physiology commits a crime against mankind.”3
Animal research as a moral dilemma
In this letter Darwin succinctly summarized the ethical dilemma that is the core of the debate on using animals for research: whether we may cause harm to animals if it is necessary to advance science and medicine.
In fact, the ability to suffer is generally accepted as the sin-gle most morally relevant criterion when animals are con-sidered as subjects of moral worth. This reasoning is based on the philosophies of Jeremy Bentham who’s thoughts on this matter culminated in the aphorism: “The question is not, Can they reason? nor, Can they talk? but, Can they suffer?”4
Today, animal welfare legislation is based on this notion in most countries, which has fundamental consequences on how different species of animals are protected by these reg-ulations. For example, in the EU, only the use of animals within the taxonomical subphylum Vertebrata (i.e. verte-brates) are covered by the respective EU directive.5 More recently also the use of Decapoda (e.g. crayfish, crabs, lob-sters) and Cephalopoda (e.g. squids, octopuses) falls within this regulation since it is assumed that these animals have a complex enough nervous system to perceive pain and expe-rience suffering.
Most current legislation in industrialized countries ac-knowledges that animals (not exclusively, but especially those able to suffer) have intrinsic value and a moral sta-tus that is different from other biological forms of life such as plants, fungi or bacteria and inanimate matter. At the same time no country has established legislation that con-siders the moral status of any animal the same as the moral status of a human being – irrespective of the developmental state or status of health of that human being.
Together this reasoning has led to the appreciation, that leg-islation cannot reflect a general rule of “one size fits all”, but a compromise needs to be implemented, where ethical and scientific judgment for each individual experiment or study is made on a case-by-case basis.
Adherence to the 3R-principle is necessary but not suf-ficient for ethical justification of laboratory animal use
The moral dilemma of inflicting harm on animals to ad-vance knowledge and medical progress was addressed in more detail in 1959, when William Russell and Rex Burch published “The principles of humane experimental technique”, in which they formulated the now famous 3R-principle for the first time: Replace, reduce, refine.6. This principle acknowledges human benefit from animal exper-iments but provides a guideline to minimize suffering in animals: Only if there is no alternative method to achieve the scientific goal, all measures to reduce the necessary number of animals in a given study, and the best possible conditions to confine suffering to the necessary minimum have been established, an experiment can be considered as potentially ethically justifiable. Meeting the 3R criteria is, however, a necessary but not sufficient requirement for eth-ical justification of a particular experiment.
Today the 3R-principle is well accepted worldwide7 as a formula to minimize animal suffering and has become an integral part of EU animal welfare regulations, which have been translated to national law in all EU member states.
Responsibility towards human life and safety – lessons from history
Another key aspect of research involving the use of ani-mals is human safety, especially in the context of medical research on humans. The atrocities of medical experiments on humans in Nazi Germany has led the international com-munity to implement strong protection of human subjects and patients. In addition, drug scandals like the thalidomide birth defect crisis in the 1950s and 1960s have led to pro-found changes in drug regulations. The results of this pro-cess have been condensed in the “Declaration of Helsinki”
adopted by the World Medical Association (WMA) in 1964. Importantly, this declaration states that medical research on human subjects is only justified if all other possible sources haven been utilised for gaining information about efficacy and potential adverse effects of any new experimental ther-apy, prevention or treatment. This explicitly includes infor-mation gained from experiments with animals,8 which has additionally been addressed in a dedicated statement by the WMA on animal use in biomedical research.9.
In analogy to the Helsinki Declaration, which has effec-tively altered the ethical landscape of human clinical re-search, members of the international research community have adopted the Basel Declaration to acknowledge their re-sponsibility towards research animals by further advancing the implementation of ethical principles whenever animals are being used in research.10 Further goals of this initiative are to foster trust, transparency and communication on ani-mal research.
Fostering an evidence-based public debate on the ethics of animal research
Transparency and public dialogue is a critical prerequisite for a thoughtful and balanced debate on the ethical implica-tions of using animals in potentially harmful experiments.
However, a meaningful public debate about ethical consid-erations is only worthwhile, if we agree on the facts regard-ing the usefulness of research on animals for scientific and medical progress.
Yet, the contribution of animal models and toxicology testing to scientific and medical progress as well as sub-ject/patient safety is sometimes doubted by animal rights activists. Certainly, in most biomedical research areas, in-cluding those that involve animal experimentation, there is room for improvement, e.g. on aspects of reproducibility or translation of results from bench to bedside. However, there is widespread agreement among researchers and med-ical professionals, together with a large body of published evidence, on the principal usefulness of animal models in general. As for all science, constant improvement of mod-els and careful consideration of whether any model used is still state of the scientific art at any given point of time is crucial for scientific advancement. Also the responsibility to avoid animal suffering as much as possible dictates that new scientific methods and models free of animal suffering are developed with both vigour and rigour.
A fruitful debate needs to be based on these insights and evidence-based common ground needs to be established when discussing ethical considerations and stimulating new ideas. Finally, we need to acknowledge that we are always in the middle of a continuing thought process, in which we very democratically and carefully need to negotiate the importance of different views, values and arguments.
 Johnson, E. M. Charles Darwin and the Vivisection Outrage. The Primate Diaries (2011).
 Feller, D. Dog fight: Darwin as animal advocate in the anti-vivisection controversy of 1875. Stud. Hist. Philos. Sci. Part C Stud. Hist. Philos. Biol. Biomed. Sci. 40, 265-271 (2009).
 Darwin, C. R. 1881. Mr. Darwin on Vivisection.
The Times. (18 April): 10. (1881). Available
at: http://darwin-online.org.uk/content/frameset?pageseq= 1&itemID=F1352&viewtype=text. (Accessed: 25th October 2017)
 Bentham, J. An Introduction to the Principles of Morals and Legislation. (W. Pickering, 1823).
 DIRECTIVE 2010/63/EU OF THE EUROPEAN PARLIA-MENT AND OF THE COUNCIL on the protection of animals used for scientific purposes. 2010/63/EU, (2010).
 Russell, W. M. S. & Burch, R. L. The principles of humane experimental technique. (Methuen, 1959).
 Guidelines for Researchers. ICLAS Available at: http://iclas.
org/guidelines-for-researchers. (Accessed: 29th November 2018)
 WMA – The World Medical Association-WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. Available at: https://www. wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. (Accessed: 29th November 2018)
 WMA – The World Medical Association-WMA State-ment on Animal Use in Biomedical Research. Avail-able at: https://www.wma.net/policies-post/wma-statement-on-animal-use-in-biomedical-research/. (Accessed: 29th November 2018)
 Basel Declaration | Basel Declaration. Available at: https://www.basel-declaration.org/. (Accessed: 30th November 2018)