Category: 3Rs

Today is Being Open about Animal Research Day, #BOARD21. If I can pretend to speak on behalf of my institution, this is what I would say about us. This is what I’m trying to act in line with.

We do research with animals. We also develop non-animal models for biomedical research. Transparency means talking about both, in a way that is as unbiased and as honest as possible.

I’m not a typical researcher using animal models, and my way of being open about animal research will be particular for my own professional self and context.

I’m an animal welfare scientist in a biomedical research institution, i3s – Instituto de Investigação e Inovação em Saúde. I have worked in this organization for 20 years, I have learned a lot, unlearned some, and hopefully achieved one thing or another in terms of institutional culture, practice and infrastructure.

My greatest passion in the field is the research we develop to improve animal welfare, and in particular our research into survival of laboratory mouse pups. This is the topic I have worked on for the longest time, and it has brought fantastic collaborations with great colleagues and outstanding research institutions. At the point where we are now, I’m also believing our research finding can bring about change.

But changing the world through research is a very slow process. Training is much more impactful – or at least so I hope, since this is the other main part of my work. My institution has hosted a training course in laboratory animal science for researchers working with animals since 2005. It makes a huge difference for the mindset and for the standard that everyone who works with animals has been extensively trained to do so. It helps to create a spiral effect where knowledgeable researchers demand high quality support from the animal facility – and the animal facility can set high standards for how animals are treated in research. For us, adhering to international accreditation schemes – FELASA for our training course, AAALAC-International for the animal care and use program as a whole – has been crucial to keep up the quality and to improve.

Institutional measures to promote quality in research with animals are important. The same is true for quality in animal care. Working with international accreditation schemes (FELASA, AAALAC) help us to keep up the quality and improve.

But there is a lot more we can do.

I would like to know that all researchers when planning their research think carefully about what the right model is to address their research questions. And that they get support in this – that they are challenged to think, that they have experts to “think together” with, and that they get expert support in implementing the models. This should be the case for both animal and non-animal models.

I have a vision for how to achieve this within my own institution. To get the entire research community to think this way is beyond my reach, but of course it’s an important ideal.

In the meantime, I wish for all of us to be honest about what we do and what we can achieve. There are problems in practice with animal model research and problems with non-animal model research. We should work to prevent and overcome these problems, and not deny that they exist, or act as if they only happen in one type of research. There are limitations of animal models and limitations of non-animal models. If we speak about the limitations of one, we should also speak about the limitations of the other. Selective use of facts is not good practice in science communication. But it’s far too common in the discussion of animal experimentation – on both sides of the debate.

Why are we recording a video of my colleague Rita Santos painting the back of a white IKEA mouse with a black marker pen?

The background story is that nearly 50 years ago, in 1974, a US researcher painted real laboratory mice as part of what has become a well known story of scientific misconduct in biomedical research. The story isn’t as well-known among biologists and animal scientists as it is among immunologists (or at least so I assume, based on anecdotal evidence = whom among my contacts and colleagues who were or were not aware of it when I asked), despite being both striking and somewhat sad.

Striking, because once you’ve heard the story, you are likely to remember it. Dr William T Summerlin was doing research into transplantation immunology. He believed that by keeping the tissue in laboratory culture for some time before transplanting it into the recipient animal, it could be transplanted without rejection. His proof-of-concept experiment was to graft skin from black mice to (genetically unrelated) white mice. Did he actually ever transplant skin? I don’t know – this amount of detail is not given in the easily accessible internet sources. But what is very clear is that his demonstration of success was a fraud. An attentive technician discovered that the black patch on the back of the white mouse could be rubbed off with ethanol. As reported in this NY Times account of the case, published only a month later, Summerlin admitted to having painted the mice.

Sad, for a number of reasons, going beyond the actual misconduct itself, which is of course in itself highly lamentable. The painted mice seems not to be a one-off event – when Summerlin was investigated the committee also discovered a seemingly very dubious case of cornea transplant experiments in rabbits. Whereas having their backs painted would hardly have harmed the mice, the failed cornea transplants must have caused the rabbits pain. And none of this was justified. Scientific experimentation is not about simply trying something to see if it works: there has to be a reasonably developed idea of what mechanisms are involved. I don’t find any reference to a theory about mechanisms involved in the purported transformation of a xenograft (from a genetically different individual) into tissue that is not recognised as foreign when transplanted into a recipient. All that is to be found is that Summerlin had claimed for some years that he had a method for laboratory culture of tissues that removed the problem with transplant rejection, and that other researchers were unable to make the procedure work when they tried to repeat it in their own labs (a classic way through which fraudulent or poorly conducted research is discovered). The requirement that an experiment is based on a reasonably developed theoretical framework and previous, related studies is even stronger when the health and well-being of living beings are involved.

Why, then, are we painting mice? As part of the INTEGRITY project, we are developing teaching material into ethics and research integrity issues in animal experimentation, for high school students, ready for road testing in about a month. And please note, we’re not painting mice, we’re painting toy mice. The first R, Replacement, of the 3Rs principle of course. Knowing what mice are like, I actually believe that using real mice for this purpose would not only have been stressful for them but a pain for us!