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The use of monkeys is still common today in the fields of fundamental research and neurology. We face the same age-old ethical dilemma : their « similarity » to humans supposedly makes them good models monkeys but also raises difficult ethical questions. But from a purely scientific perspective, are monkeys actually good models for the study of human disease ? Below is the opinion of someone who is a medical neurologist, researcher and teacher.

Dr Colette Goujon is consultant neurologist at the Henri Mondor hospital, specialising in the management of chronic pain. She is also a research fellow at the Faculty of Medicine in Creteil and is the author of several peer reviewed articles and book chapters on the subject of chronic pain management.

Antidote Europe (AE) : Were you ever required to perform animal experiments in the course of your medical studies ? If yes, how did you manage to avoid them and still pass your medical exams ?

Colette Goujon (CG) :
In our second year medical studies we studied anatomy by dissecting human cadavers. I was never required to perform animal experiments during my medical studies, nor during my specialisation in neurology. It is fortunate that I never had to deal with this issue during my studies because I would have refused to participate.

AE : You recently attended a public hearing in the French parliament on the subject of animal experiments. According to one of the speakers, we need to study monkeys in the field of neurocognition. What are your views on the subject ?

CG : « Primates are phylogenetically close to humans » and thus regarded as having predictive value with respect to human response in the field of biomedical research. However :
Despite similarities between the DNA of chimpanzees and humans, there are important phenotypic differences that exist between species with regard to their genetic make up and disease. These in turn can influence the metabolism and the efficacy of pharmaceutical drugs.
In the field of neuroscience, where we explore the role of various structures in the brain, specifically related to decision making, motivation, judgement and emotions, many studies have been conducted in animals, particularly in nonhuman primates. But the translation of these laboratory experiments to humans remains very challenging, not only because of differences in cerebral structures in the cortex, but also because of different cognitive perception in animals. The latter are poorly understood and difficult to explore because animals do not share our language.
In addition, huge advancements made over the last 20 years in the field of non invasive brain imaging has provided neuroscientists with new insights into how brain networks are organised. As a result, data from monkey studies pale in significance when compared to human cognitive studies. The best experimental model for the study of humans is ourselves.

AE : Large amounts of funding are still allocated to animal research in the field of brain function. What would you consider to be a fairer way to allocate such funding ?

CG : As I am not involved in fundamental research, I am perhaps not the best person to ask this question. However, I would say that the lack of funding for the development of methods to replace animal use are a major obstacle to progress, for several reasons : lack of private and public funding ; lack of awareness of replacement techniques among clinicians ; lack of awareness on the part of the media and the general public of the existence of these replacement techniques.
To help remedy the situation, it is important that public funding be invested in human-relevant, evidence-based technologies such as microfluidics and organ-on-a –chip. These technologies will help to speed up the replacement of animal models.

AE : You are currently in practice as a neurologist who is regularly confronted by patients with serious neurodegenerative diseases, such as Alzheimer’s. What is your advice in terms of how we can better prevent these diseases ?

CG : Neurodegenerative diseases do not belong in a single category. Many of the articles written on the subject of prevention are contradictory. However, there does appear to be a general consensus on the need to adopt lifestyle measures associated with a decrease in known risk factors, such as : smoking, excess sugar and fat in the diet, lack of physical activity, and obesity, which is often associated with hypertension.

AE : We sincerely thank you for your time. Are there any other thoughts that you would like to share with our readers ?

CG : Questioning the status quo is an important stepping stone towards freedom of thought and action.
Scientists should be the first to realise that animals are not a good experimental model for man. Although many scientists now acknowledge this, some continue to promote animal research. « Animal models persist because of historical and cultural reasons. While non animal replacement models must undergo an officially recognised validation procedure prior to regulatory acceptance, animal models are accepted on the basis that they are predictive of human outcome. » (Andrew Knight)
The cornerstone of good research is that it be based on critical thinking, but changing habits costs money and requires time.
Some clinicians are far from convinced that animal experiments produce relevant results and are generally critical of such studies on moral grounds, on the basis of animal suffering. However, these individuals often feel isolated and are not sufficiently knowledgeable about available replacement techniques to enable them to challenge animal researchers.
We should aim for the complete abolition of animal experimentation. This goal would signal a awareness of our moral responsibility towards our fellow creatures and a sign of humanity’s progress.

References :
Knight Andrew. Animal Experiments Scrutinised: Systematic Reviews Demonstrate Poor Human Clinical and Toxicological Utility. ALTEX, 2007, special issue, n° 4, p. 320-325.
https://www.researchgate.net/publication/5564513_Animal_experiments_scrutinised_Systematic_reviews_demonstrate_poor_human_clinical_and_toxicological_utility
Schwamborn Jens C. Is Parkinson’s Disease a Neurodevelopmental Disorder and Will Brain Organoids Help Us to Understand It?
Stem Cells and Development 2018 Vol. 27, No. 14
Shanks N, Greek R, Greek J. Are animal models predictive for humans ? Philosophy, Ethics, and Humanities in Medicine 2009, 4:2.

Dr Andreas Ganz obtained his medical degree in Germany in 2002 and subsequently studied psychiatry, internal medicine and neurology. After obtaining a Masters degree in health administration in 2009, he went on to specialise in psychiatry and psychotherapy.

Since 2017 he is chief physician of the Prinzregent-Luitpold-Klinik in Bad Reichenhall / Germany, with a focus on psychosomatic medicine. Dr Ganz has been a member of the German association Doctors Against Animal Experiments since 2016.

Questions :

Antidote Europe (AE) : You obtained your medical degree and you specialised in psychiatry without

taking part in animal experiments. Would you say that animal experiments should be completely excluded from the curriculum for human medicine ? On what grounds ?

Andreas Ganz (AG) :

From my personal point of view – and from my personal experience as a graduate, there is absolutely no benefit for the students. All physiological and biochemical processes can nowadays be demonstrated in a more specific and descriptive way for students with corresponding didactic techniques (Computer simulation, Multi Organ Chips, biomechanical simulations etc.) Demonstrations on the animal model are therefore more of a hindrance to medical education and impart a wrong approach to cure human deseases. In other words, animal experiments in human medical education are not only a waste of life – but also a waste of time and resources. Thus, there is no ethical or practical justification for this.

AE : you are a member of Doctors in Germany Against Animal Experiments. How does it feel to be part of the largest group of doctors and researchers (600) in Europe campaigning for an end to animal experiments ? How do you see your role in the organisation ?

AG :  Of course, it gives me a good feeling to work with others towards a goal that I strongly identify with. There is a lot to do – the biggest mistake anyone can make is to do nothing because he thinks it will achieve too little!

The focal points of my contribution to this organization are my experience and my knowledge in the field of psychopharmacology; and aspects of the health economy that are a reflection of the huge economic damage resulting from the animal model paradigm.

AE : What in your view is the biggest obstacle to ending animal experiments ?

AG : Well – decision-makers in business and politics usually do not know enough about the colossal health and economic potential of animal-free methods. And on the other hand, the protagonists of the Animal Research lobby in their strategic positions have no interest in “passing” this knowledge on to the decision makers. Therefore, virtually nothing has changed on the practical level.

Our task is and will be to bring this knowledge to the right people in the places.

AE :  Are there any other thoughts that you would like to share that were not covered in the interview ?

AG : In my view, animal experiments are a mixture of antiquated-dogmatic nineteenth-century thinking and superstitious notions that animal sacrifices are necessary for the success of a scientific endeavour… which is unworthy of an empirically-enlightened working method.

The protagonists of animal based research should learn from history the lesson that it has never been possible to overcome the challenges of tomorrow with methods from the day before yesterday.

AE : We sincerely thank you for your time for this interview.

“The mouse intestine is different to the human one. If you want to study absorption of nutrients or drugs, then a mouse system is not appropriate”

Dr. Tamara Zietek works as Scientific Officer for the German NGO Doctors Against Animal Experiments (Ärzte gegen Tierversuche e.V.) and lives near Cologne, Germany. She is an expert for human-based, animal-free in vitro technologies in the field of biomedical research and has been invited as a speaker to a number of international scientific conferences. In the past years, she published numerous articles in international scientific journals, scientific book chapters as well as articles for the broad public. Dr. Zietek holds a PhD in biochemistry and worked as a research group leader at the Technical University of Munich for 8 years. During her time as a researcher, she established the intestinal organoid model (mini intestines grown in the lab from human tissue biopsies) for studies on nutrient and drug absorption as well as for research on metabolic disorders such as diabetes and obesity. At the beginning of her career at the Technical University of Munich, Dr. Zietek observed mouse experiments. Based on her personal observations, she realised that these animal experiments were a failure and that human-based models are the answer to human-relevant questions.

Antidote Europe (AE) : For the past two years, you have been studying human intestine derived from surgical waste. Could you share your experience with our readers regarding the logistical obstacles you needed to overcome in order to obtain these human tissues (ethical committees, paperwork, finding surgeons willing to collaborate) ?

Tamara Zietek (TZ) : The formal hurdles are really high if you want to grow human organoids – no matter which tissue they are derived from. It took us more than one year of administrative work until we finally had the tissue in our lab and could start growing intestinal organoids. First of all, you need to find a surgeon who is willing to collaborate. These doctors are rare as a lot of them perceive it as a nuisance to care about special tissue handling etc. during surgery. Luckily, the Technical University of Munich has a University hospital so it was a question of networking with some professors to finally get in touch with our collaborating surgeon. Subsequently, there were a number of formal steps including contracts with the hospital, with the pathology department and with the ethics committee – a lot of paper work indeed. After final approval by the ethics committee, we needed to organize the logistics. It is essential that the collaborating hospital is situated near your lab because the isolated tissue is sensitive and needs to be delivered to the lab within a few hours. In our case, the hospital was approximately 30 km away from our lab, so we organized a taxi transfer. Another issue is that the tissue is not delivered at regular intervals, sometimes we got biopsies twice a week and sometimes every 2 weeks. In addition, you are informed by the hospital at very short notice that a biopsy will be delivered. Finally, you must ensure that there is always someone in the lab to accept the delivered material.

AE : The use of animals is unfortunately still widely considered to be the current paradigm in biomedical research. Would you say that it is much easier for researchers to obtain authorisation to experiment on 100 mice than to obtain authorisation to obtain human surgical waste ? If yes, what needs to change in the system to make it simpler for researchers to access human tissues ?

TZ : I think, if a researcher wants to start working with mice beginning from zero, it is also complicated and associated with a lot of formal obstacles. But this is very rarely the case, because usually, most universities and scientific institutes have an in house animal facility which can be used by all departments. In this case, it is definitely easier to start running an animal study compared to a project involving human subjects.
It would be helpful to have a biobanking system for human tissue. Unfortunately, tissue for growing organoids cannot be stored for a long time. It would therefore be helpful to have a centralized approach at universities and research institutions – similar to an in house facility. This would be a great advantage for researchers because they would only need to make a agreement with this core facility. whereas collaborating surgeons for different tissue types, contracts with hospitals and the ethics committee for different scientific purposes as well as logistics would be organized by the core facility. It should be noted that such an approach would only make sense if many research teams at the institution worked with human tissue.

AE : You decided to leave your previous job because you did not want to perform animal experiments. Is your objection to the use of animals based on ethical or scientific grounds, or both ? Do you remember a specific time in your career when the use of animals started to ring alarm bells ?

TZ : It was both, ethical and scientific reasons for which I finally stopped working on projects involving animal studies. I never wanted to conduct animal experiments – for ethical reasons. Therefore, in my diploma thesis, I worked with microorganisms (bacteria and yeast) and in my PhD thesis with microorganisms and plants. When I started working at the Technical University of Munich, I was asked to supervise some PhD students who worked with mice. Although I did not perform animal experiments myself – that was the job of my technicians and PhD students – I supervised the projects and did never feel well with that. But the more data I saw from the mouse experiments, the less confidence I had that this is a good « model system ». I was astonished about the high inter-individual variability of the data. And also about the missing robustness of this model. I often wondered why we were not able to reproduce the data from mouse experiments published by others, although we did everything exactly as described in the paper. After speaking to other researchers who were working with animals, I learned that this is a very common problem. There are scientific publications showing that mouse experiments deliver totally different outcomes depending on the lab room where the animals are housed beforehand. I also learned that inter-species differences are a big problem. In many publications you find the argument that certain experimental findings differ from another paper because the study was conducted in another species – e.g. rats instead of mice. Divergent experimental results are also explained by different genders. So I had a really hard time believing that data from mice can be easily tranferred to humans.

AE : Could you describe the advantages of using human intestine organoids over the use of living animals or animal tissues ? What interest is being shown by the pharmaceutical industry to the application of human organoids in drug development and research ?

TZ : The mouse intestine is different to the human one. If you want to study absorption of nutrients or drugs, then a mouse system is not appropriate. It hence makes sense to use a human in vitro system for studying such mechanisms. Furthermore, data obtained from human intestinal organoids show better reproducibility over animal experiments. Organoids can be generated from individual patients with gastrointestinal diseases and this allows therapeutic approaches in the form of personalized medicine. Scientific questions related to inflammatory diseases or malabsorption syndromes and also to diabetes or cancer can be targeted. The so-called micro-tumor-technology is already applied for clinical purposes and cancer therapy. Tumor spheroids are grown from patient biopsies and used either in drug development for the screening of novel agents or for the identification of the most effective drug against a patient-specific tumor type.
Pharmaceutical companies are very interested in human organoid models or other human based 3D cell culture models. In contrast to animal experiments, theses models provide human-relevant data, they show better reproducibility, are suitable for high-throughput screenings, cheaper and less time-consuming. The pharmaceutical industry supports the development and validation of organ-on-a-chip systems, where human-derived cell culture models of different tissues are combined on a biochip platform and connected via a microperfusion system simulating the blood circuit and the urinary circuit. Recently, a 10-organ-chip was developed with brain, liver, kidney, intestine etc.
Such approaches are highly innovative and have huge future-potential for human medicine.

AE : Thank you so much for this very interesting interview.