Painting mice

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!

Of hens, mites and teabags: Interview with Francesca Nunn

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Congratulations Francesca Nunn to the NC3Rs Prize! You were awarded this prize for your work on a new approach to testing treatments against red poultry mites. Tell us more about the project!

Poultry red mites are parasites that live in hen houses and emerge at night to bite hens and consume blood. There are a number of studies ongoing worldwide to develop new ways of controlling the mites but this is a really tricky host:parasite model to work with because the mites spend most of their time off of the host. To help with this, we needed a technology which kept small numbers of mites on the host and allowed feeding and recovery of the parasites. The NC3Rs funded project was to optimise and further develop a prototype “on-hen feeding device” that had achieved ~50% mite feeding in a pilot study. This device allows accurate assessment of mite control methods on small numbers of hens before conducting field studies, for example. This addresses “Reduction” by greatly reducing the number of hens used, as it would accurately identify poorly performing mite control methods before they were progressed to field trials. This system can also be used to test the effectiveness of mite control methods across prolonged periods on small numbers of hens (4 per treatment group, as opposed to 400 per treatment group in field trials) without continually exposing birds to the parasites. This therefore addresses “Refinement” as it allows the birds to remain free from the parasites, with parasites only accessing the birds for short (3 hour) periods every 3 weeks instead of the continual exposure encountered in field trials. The project involved developing the device for all the blood feeding mite stages as well as studies to optimising feeding rates, minimising background mite mortality and using the device in trials to test its performance.

Your approach allows a huge reduction in animal numbers. What about animal welfare? What would a traditional test approach be like for a hen, and what will she experience with your refined method?

Novel systemic acarines or vaccines are tested on hens using an experimental infestation model. This involves releasing a set number of mites into a cage of hens, and then monitoring the mite population growth over time. And of course, you’d compare the treatment group to a control group. This means that the experimental hens are exposed to thousands (often tens of thousands) of mites over a number of weeks. As we know, mites cause discomfort and stress to the hens which is why we need the treatment in the first place! Using our feeding device, the hens are only exposed to 50-100 mites per time point – the rest of the time they are free to just be hens in enriched floor pens and parasite free.

Can you tell us something about where the idea came from and how you went from idea to device?

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Similar rigid devices, which were glued onto the hen had been used previously but weren’t widely adopted. This is probably due to the mites not being able to attach to the hen when the hen’s movement caused the device to move. The team at Moredun, led by Dr. Kath Bartley and Dr. Al Nisbet, came up with a tea bag type prototype which solved this problem while also managing to contain the mites. The next issue was to find a material that the mites could feed through-originally we used phytoplankton mesh but had to find an alternative that allowed the much smaller nymph stages to feed also without escaping.