The Dean of Charité, Prof. Axel Radlach Pries, discusses the need for research involving animals and the ethical imperative to explore alternative methods.
Prof. Pries, the Süddeutsche Zeitung newspaper recently published a long article which suggested that it is now possible to replace animal research with alternative methods, and that those who continue to conduct research involving animals can no longer be considered to be working at the forefront of science. Is that true?
No, that is definitely not true. The situation we are in is one in which animal research continues to be crucial to the development of new treatments and diagnostics. There are many examples of state-of-the-art treatments, including cancer treatments, where it is possible to deduce the type of research responsible for what are often pioneering drugs. It is entirely inconceivable that insights gained in this manner could have been gained without resorting to animal research. There continues to be a definite need for animal research. However, that fact is just one side of the coin. The flip side is that where animal research is unavoidable, experimental conditions must be optimized – refinement being the key word here. Similarly, we must also continue to increase our efforts to develop alternative methods. This will enable us to gradually replace animal research through the increased use of alternative methods.
These are precisely the aims of Charité 3R. What is driving you personally to be such a vehement advocate of the principles of the 3Rs – Replacement, Reduction and Refinement?
I’m a physiologist by trade and simply reached a point in my career where animal research became unavoidable. Computer modeling did enable me to increase my research output while also reducing the number of animals needed for this research. Yet, the ethical issues involved continued to weigh heavily on me. There is a need for animal research within a certain context. That much is true. But it isn't something that one finds easy to do or that one enjoys doing. Another crucial experience was the political debate surrounding the question of how to approach animal research. I noticed that, while I had no problems stating that, at this moment in time, animal research remains unavoidable, I was not able to say I am convinced that we are doing everything in our power to find alternatives.
And this prompted you to launch the drive to establish Charité 3R. How unique is what you are doing?
We certainly cannot claim exclusivity in this area or claim that we set things in motion. There are other bodies which are pursuing initiatives in this field, particularly in Berlin, which has long been a center of expertise in the area of alternative methods. In that sense, we are part of an emerging trend. However, a university faculty voluntarily committing to creating such a large facility, and so quickly, is something that really sets us apart.
Which of the 3Rs do you consider the most important?
I think ‘refinement’ is the area where the need is greatest. Money is hard to come by, as there is very little funding support available. It is for this reason that Charité 3R has already provided funding for seven projects since it was launched in November 2018. All of these projects pursue different approaches aimed at improving the quality of life for research animals. I realize of course that this is only a drop in the ocean. But it’s a start; and an important one at that. After all, much of what we do is to sow the relevant seeds. We want to show what is possible. And what is possible can and should be used to develop many new ideas.
To inspire others to copy them?
Of course. This will all be pointless unless the entire scientific community gradually changes course. And I very much include scientific journals in this. Research which is based on alternative methods remains difficult to publish, with journals frequently insisting on additional research involving animals. This must change. Scientific freedom is of immense value. Sometimes, a little push is needed for systemic change to happen; something which will speed up the implementation of strategic objectives and – hopefully – produce lasting change. For me, the electricity market provides a perfect example. Thanks to feed-in tariffs which encourage alternative electricity generation, our electricity now comes from a mix of renewable sources. Without help, this would not have happened, or only very slowly. Charité 3R has nailed its colors to the mast in this respect. We want to promote this type of paradigm shift, both on the national and the European level.
What has been happening in the field of non-animal-based alternatives?
There have been a range of developments. These include organ-on-a-chip and in silico technologies, but also something that is being actively pursued at Charité 3R, by Prof. Hippenstiel: the use of ex vivo tissue. This is human tissue collected during normal surgical procedures which, once it has delivered the relevant answers, is excess to requirement. It forms a hugely important part in the development of real alternatives. We were recently successful in securing a total of €34 million in funding for the ‘Der Simulierte Mensch’ [‘The Simulated Human’’] research building. The project will see us work with TU Berlin [Technische Universität Berlin] and will aim to develop precisely these types of non-animal-based alternatives by placing the focus firmly on the simulated human as an experimental model. So, there is plenty going on already. But it all takes time. Low-quality wind turbines, used in the wrong context, won’t achieve a thing. Systemic change can only happen once we have good and reliable alternatives. This is why Charité 3R selects research projects based on a highly competitive selection process involving external experts. This process ensures that the selected research is of an extremely high standard.
An important aim of Charité 3R is to improve the quality of research in general. Will this improve the quality of animal research or even reduce the need for such research?
The QUEST Center, which is being led by Prof. Dirnagl and funded by the Berlin Institute of Health, is committed to finding ways of improving the scientific quality of both animal-based research and alternative methods. One thing we do know, for instance, is that stress leads to an inflammatory response in research animals, and this will distort results. It is also possible for a piece of research which uses 6 animals to be unethical because it would not be statistically robust or repeatable, while an experiment using 15 animals might mean the research is reproducible and thus the correct way to go. While one objective is to improve both the quality of the research and its reproducibility, the other is to avoid any animal research that is unnecessary, and to reduce the suffering of animals used in research. QUEST truly is a unique undertaking and works very closely with Charité 3R.
The article mentioned at the beginning of this interview quoted a renowned professor who claims that 95% of all animal research produces results which are not transferable to humans. Does he have a point?
That is a knockout argument used to kill all discussion. The transferability of research results to humans always presents a challenge. Clinical trials involve hundreds, if not thousands of patients. And why? Because findings are not even transferable between one individual to another. Research using reduced mouse models, in which the animals are young and kept in germ-free conditions, can effectively only produce one positive argument: “Well, it works here!” At Charité, we are currently working with external partners to explore the option of keeping animals in larger groups and natural conditions, to ensure that we can study disorders in what will still be a strictly controllable yet far more realistic environment. These types of projects represent an enormous challenge, and we will see what effects this will have on transferability.
Would you say that the researchers working at Charité share your enthusiasm?
Well, there are certainly many who find the subject area extremely interesting. Our first call resulted in responses from more than 100 interested parties. But we don't just want to convince as many as possible. We are striving for the best case scenario, which will see us convince everyone and make it quite clear that we do not just offer a program of enormous scientific interest; rather, that we are also committed to promoting and supporting innovative, sustainable ideas. Once we have achieved that, we also want to win over the larger research funding bodies to join us and deliver this game-change. The idea is to get everyone to commit to a type of 'feed-in tariff’.
Researchers who use animal research often face serious levels of hostility. What is your take on this?
It is extremely important to me that researchers whose work involves the use of animals are seen as committed to the same ethical standards and values as those who work towards alternative methods. This also applies, without exceptions, to other members of staff who work in facilities involved in animal research. They are equally deserving of our full respect, as they are equally as dedicated to our common aim of achieving medical progress. At least 80 percent of our drugs were developed using animal research. This is why I absolutely cannot understand colleagues working in the field being castigated and consigned to society's sin bin. In my opinion, they deserve precisely the opposite – our support! After all, we are all working to advance biomedical research. Similarly, it is incumbent upon the entire community to promote alternatives. That may well involve having to put 10 percent of available resources into promoting alternative methods or improving animal welfare. There is an urgent need to consider a system of subsidies. I believe our researchers understand and accept that this is an issue which will require serious and ongoing debate.
And what has been the public reception of Charité 3R?
We are in the process of building our credibility. Everybody should know that we are doing everything in our power to render animal research unnecessary, even if, at this point in time, we still regard it as indispensable. There will always be people who say: “Animal research, it doesn't work!” On a number of occasions, however, I have personally witnessed political debates which resulted in critics or opponents of animal research approving of the approach taken by Charité as being a very good one.
(author: Beatrice Hamberger)
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