We don’t need animal experiments! We get our drugs from the pharmacy!

Research using animals is a sensitive issue. Anyone who does animal experiments, like myself, is reluctant to talk about it, at least outside our natural habitat, the laboratory or scientific conventions. Institutions where animal experiments are carried out are also quite shy about the topic. Recently, the Max Planck Society left Nikos Logothetis (MPI Tübingen) standing in the rain when he was targeted by a media campaign. Now he and some of his laboratory staff are off to Shanghai… The websites of prominent research institutes feature all kinds of colorful illustrations showing immunohistochemistry slides, doctors and students in white coats with pipettes in their hands, sitting at computers or their microscopes. But rats or mice are conspicuously missing! They proudly display their research activities, and enthusiastically advertise (future) research breakthroughs towards completely new and effective therapies. But no reference is made to animal experiments on campus!

That is quite remarkable. Isn’t the only justification for breeding, housing, sometimes harming, and killing animals in research that all this serves to improve our knowledge of biological processes so that new and better therapies can be developed? This of course includes basic research, which after all is the basis for translating knowledge into medical progress. Often this is illustrated by referencing many Nobel Prizes awarded for medical progress based on animal experiments. A large part of the achievements of modern medicine resulted from or made use of animal experiments. For neurology, my expertise, I posit that at least 50% of the therapies which save lives or help to maintain quality of life in patients with brain diseases (e.g. MS, Parkinson, epilepsy) would not be available without prior animal experiments.

This is certainly not a carte blanche for every animal experiment that is merely labelled as potentially providing knowledge for future human medical benefits. Consider, for example, a study recently published in Nature by stem cell and regeneration researchers from Harvard and Sao Paulo. In their experiments, mice were exposed to a variety of torture methods developed in Nazi concentration camps and still used by the CIA. Mice were fixed for many hours, constantly switched between new cages, isolated, damp bedding was thrown into the cages, the cages were tilted, bright light changed in short intervals with darkness, all this in unpredictable sequence or in combination and over many days. In other groups mice were simply injected with a substance inducing severe pain. In the article all these measures are charmingly called ‘stress procedures’. And what was the point of the study? The authors found that stress causes hair to turn grey, that this process is mediated by the sympathetic nervous system, and that melanocyte-producing stem cells, the cells that produce the dye, break down! Whoever finds this surprising has slept under a stone for the last 100 years while stress research has progressed. The animal ethics committees of all participating institutions had given their blessing to this study. Is this therefore ethically justifiable? No – even if in the future it might help to develop a shampoo which slows down the formation of grey hair in old age. Or helps torture victims in Guantanamo maintain their hair color despite torture and deprivation.
There must be a healthy proportionateness of possible benefit for humans and the suffering inflicted to animals. The specifics of such relationships are certainly not easy to define, or to ethically defend, but there must be clear limits. There are experiments that are so cruel that they should not be done to animals, no matter what the benefit for humans is. It is not surprising that the IRBs of scientific institutions do not see any ethical problems when their star scientists carry out experiments and publish them in Nature. What I do find surprising, however, is that the world press has highlighted the study quoted above with great acclaim, often illustrated with pictures of cute mice staring at a piece of cheese.
Many people object that animal testing may have been necessary in the past, but can today be replaced by alternatives. The logic of this argument is undoubtedly correct: If we were able to advance our understanding of biology and disease mechanisms without the use of animals, animal experiments would not only be obsolete but unethical. However, even in the age of organoids, iPS cells or computer simulations of biological systems, this is still fiction in many cases. Especially the complex interaction of blood circulation, immune system, and brain activity, which modulates practically all cell and organ functions, and thus influences almost any disease, cannot be modelled in vitro, at least not yet. However, the emphasis must be on ‘yet’, and many processes, especially in less complex organs than the brain (e.g. liver, lung) can already be modelled quite well in a dish. Therefore, developing alternatives to animal experiments must be a priority. Once validated, alternatives should replace animal experiments.
However, I cannot refrain from pointing out a few common contradictions and inconsistencies in the arguments against animal experiments. Because these contradictions discredit relevant arguments against animal experiments. The most basic argument against animal experiments is the rejection of the use of animals for human purposes on moral grounds. Only a few years ago, this position would not have been tenable in practice for opponents of animal experimentation. After all, anyone who argues in this way should not consume any animal product. But today even Lidl has a vegan department, and supplements exist to mitigate the effects of a diet for which evolution has left omnivores unprepared. Beyond diet it is more difficult to get by without animal products. But even this is feasible, as even luxury limousines advertise vegan interiors. Importantly, however, visits to the doctor or the hospital are not an option if you espouse such strict ‘humans should not use animals’ ethics. Unless of course if you don’t have a serious condition and are happy with a prescription of globules or herbal extracts.
Not surprisingly, only few people consequently follow such ethics. Others discredit their position by illogical arguments and an inconsistent life style. Not only do they happily accept treatments which were developed using animals when they or their loved ones need them, they often also own pets. And this is another relevant inconsistency of many who argue against animal experiments. Not only because they keep animals in an inappropriate environment or accept suffering of breeds: Think dogs in the city, cats in appartments, and dog breeds with facial geometries that lead to the extrusion of their tongues and eyes, or which are epileptic, and develop dysplastic hips. It seems an even more severe inconsistency to me that such animal ‘rightists’ take their pets to veterinarians for medical treatments. Vets prescribe remedies which in most cases were developed for humans using animal experiments (antiepileptics, antibiotics, analgesics, etc.). Are animal experiments justified only for veterinary medicine? And should antiepileptic or antihelmintic drugs for animals only be developed and tested in animals? The use of human drugs (or their derivatives) in animals also demonstrates that a transfer of the results between humans and animals (‘translation’) is possible in principle, which is often negated by animal rightists. The inconsistencies become even more blatant when we consider what some of our beloved animals do at night. Domestic stray cats are the main causes of anthropogenic mortality of birds and mammals on our planet. In the US alone, it is estimated that domestic stray cats kill 2.5 billion birds and 12.5 billion mammals annually. And these killings are often quite messy! To put this into perspective: In Germany slightly more than 2 million laboratory animals are used every year.
There is a consistent biocentric argument against animal experiments. Those who live vegan, free of animal products, without domestic animals and without using modern medicine are true to this ethical position. On the other hand, anthropocentric or pathocentric arguments in favor of animal experiments have an even longer history, and are morally and logically as consistent as those of the biocentric perspective. They are easier to keep up in everyday life, but this does not make them more correct, because practicability is not an ethical category. On the ethics track one can argue a lot and with sophistication, but this does not really get us anywhere. Besides ethics, there is the law. Regardless of how an individual feels about animal testing, states have created realities through specific laws on the use of animals. In Germany, the protection of animals has recently been included in the constitution. Although these laws also refer to ethical concepts, they are enforced by state power and not by logical deduction or conviction through verifiable arguments. It follows from the above that the conflict between the obligation to maintain and improve human health and the concern to avoid pain and suffering of animals can neither be resolved by legal, nor normative or ethical considerations.
But aren’t there ethical principles of animal research which are accepted by opponents and supporters alike? How about the 3Rs of Russell and Burch: Replacement, Reduction, Refinement? Their broad acceptance is of course the result of their fuzzy and non-binding nature: Opponents can insist on complete replacement, supporters on reduction and refinement. Regardless, the 3Rs are found in many policy documents, instructions for grant applications, and 3R champions are awarded prizes. The 3Rs are the current mantra unifying supporters and opponents of animal experiments. But there is a problem: The 3Rs are missing crucial elements!
The 3Rs are exclusively focused on animal welfare. What they lack is the perspective of scientific value of animal experiments! You can refine an experiment, and even reduce the number of animals, and still conduct worthless and therefore unethical animal experiments. This happens when experiments are methodologically unsound, e.g. due to a flawed study design, distortion due to missing blinding, false positive or false negative results due to too low case numbers, selective use of data, bad statistics (e.g. p-hacking) or misinterpretation (e.g. HARKING), if they are not published (due to NULL or negative results), or an insufficient description of results to repeat them or to assess their quality.
Therefore, 3 additional Rs are needed: Robustness, registration, and reporting. Animal experiments only become robust if they have sufficient internal validity, i.e. methodological competence and control of bias. Registration prevents data from being selectively evaluated and studies from disappearing in the file drawer, or hypotheses being formulated after the results are known. And good reporting, e.g. through adherence to guidelines such as ARRIVE, as well as the provision of original data, enables the results to be re-used and reused (FAIR principles). And safeguards that data is published at all. A recently published study by the group around Daniel Strech suggests that less than 2/3 of all animal experiments approved by the authorities ever get published. Anyone who has been in the business for a long time, or is familiar with the metaresearch literature that examines all this quantitatively, knows that there is still a lot of catching up to do in many animal studies. Daniel Strech and I have recently elaborated the need for adding the principles of robustness, registration and reporting.
But there is something else that is missing in the current discussion on animal experiments: full transparency by those institutions who use animals in their research. I am talking about university medical centers. Every university hospital and medical school should publicly state that to advance medicine their researchers conduct animal experiments. This should be featured on their websites, preferably on the landing page and not hidden somewhere. They should transparently describe their procedures, how they keep the animals, how many animals are used and which species, as well as the purpose of these experiments. And they should also state that they adhere to the 6Rs (not only the 3Rs!). Personally, I would go even further. University hospitals should include the following (or similar) statement as part of the form sheet which every patient has to sign when entering the hospital: “I have been informed that doctors and scientists at this University Hospital carry out animal experiments to investigate disease mechanisms and develop new therapies. Many therapies used at our hospital are directly or indirectly based on animal experiments.”

Crazy? I don’t think so. It is the truth. Very few patients will opt out. Many others may rethink their position on animal research.

A German version of this post has been published as part of my monthly column in the Laborjournal: http://www.laborjournal-archiv.de/epaper/LJ_20_03/28/index.html

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