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.

 

Is a positive attitude to animal research desirable?

The question is motivated by a recently published research paper in JALAAS: Attitudes Toward Animal Research Among Medical Students in the United States by David Q Beversdorf and Nellie R Adams.

The authors recruited student members of the American Academy of Neurology to fill in a questionnaire. 168 students completed the questionnaire, expressing their agreement or disagreement with a set of 14 positively- or negatively-biased statements regarding animal research. After that, they were given the opportunity to watch a video about animal research, and asked to fill in the same questionnaire again, which 108 students did. In the text box to the right, you can see examples of the statements the students were presented with.

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After having watched the video, the students were slightly more positive towards research with animals: the score went from an average of 4.0 to an average of 4.1. (A score near 5 shows a positive attitude to animal research, a score near 1 a negative attitude).

The authors do not make much out of that change (not surprisingly, it’s so small that it doesn’t really matter) but instead discuss the observation that “a substantial number of
medical students express disagreement with statements that
describe essential components of the drug and procedure
development pipeline. As described above, 13.2% disagreed
with the statement ‘New surgical procedures should be tested
on animals before they are used on people,’ and 7.2% disagreed
with ‘New drugs should be tested on animals before
they are used on people.’” They continue to conclude that “The changes in attitudes after observing the video suggests that negative attitudes can be changed, and that medical education may have a role in this setting.” If you want to read the full paper, you can request a copy from the authors at ResearchGate.

Numerous studies with bigger samples and more comprehensive approaches have measured the attitude of different publics to animal research, but the present study is novel in the choice of a very specific public: medical students. My main issue with how the study was conducted is the quite one-sided study design. The video in question is produced by Americans for Medical Progress, an advocacy organisation for biomedical research and in particular the use of animals in such research. While I think the video is quite reasonable, it definitely represents a selective use of information. That’s not surprising, as the organisation behind it is working in favour of public support for biomedical researh with animals.

Should a goal for medical education be to make students more positive to the use of animals in research? I’m really not convinced that this should be a priority. I think it’s crucial that medical students get a reasonable understanding of the role of animals in biomedical research and drug development. But that also includes an understanding of critical challenges to how useful such research is. And an understanding of why the issue is contentious.

There is no equivalent video advocating in a comparable way for the replacement of animals in biomedical research. People such as the authors behind the book Animal Experimentation: Working Towards a Paradigm Change would probably be able to produce one, and it would be as credible (reasonably so) and balanced (not very) as the AMP video.

And sadly, both of them would miss out on the most critical issue in animal-based biomedical research today: how to design studies so that the results are reliable and translate to humans.

Are you going to a conference in 2020?

The beginning of a new calendar year is usually the time to think about conferences. Calls for abstracts are about to open – or in some cases even to close. I haven’t made up my mind yet about which conferences to attend, except for two for which I have an invitation (Scand-LAS and World Congress on Alternatives and Animals in the Life Sciences) which I will honour and one I know I won’t attend (ISAE – I usually attend when it’s in Europe and this year it’s in India).

Here are the ones I’m considering:

Canine Science Forum – Lisbon, Portugal 7-10 July

It would be a first time for me and it would be well justified by my increasing engagement in research with dogs. I would be an attendee only, not a presenter, but I expect that somebody else from our research team will be presenting work. Besides, it’s in Lisbon, a 3-h train ride away, and a place where I always enjoy spending some time. Other than that, I can’t really say much since I’ve never attended before.

World Congress on Alternatives and Animals in the Life Sciences – Maastricht, Netherlands 23-27 August

This is an interesting (in more than one way) conference that I’ve attended twice before (it’s held every 3 years). In my experience, it is more of a conference on Replacement alternatives to animals than Refinement alternatives, and the focus on Replacement has been heavily biased towards animal testing (toxicology etc). Whereas I obviously think it’s great that animal tests are being replaced, I don’t really have any scholarly interest in toxicology tests. But this year I have a particular reason for wanting to be present in a Replacement context: we have a project just starting on organoids and other advanced 3D models for research. This would also be a great chance for our newly hired junior researcher and project manager to get a peek into the alternatives research community. I really should discuss with my team what to present. Maastricht is a lovely city too.

EAAP – Porto, Portugal 31 August – 4 September

Again, this is a conference I’ve never attended but one which I know farm animal researchers in Europe always have on their conference agenda. Farm animal science is my background, and this would be an excellent opportunity for a much needed update, within walking distance from home! What speaks against participation is that I’m not sure what I would be able to present, and since this is a costly conference (even when not having to pay for travel or accomodation) I need to be able to fit it into a research project budget.

Will we be meeting at any of these conferences?

Should research ethics protect non-human primates as children?

I’ve played with the idea of writing about why chimpanzees are not more protected than children. But whenever I start to develop the argument it seems absurd – anyone who knows what laboratory animal research regulation looks like knows that chimpanzees are not more protected than children! Except that I regularly come across people who argue that in Europe chimpanzees are more protected than children.

I understand where the argument comes from: there is a single regulatory framework for research with animals in Europe (Directive 2010/63/EU) but not for research involving children. Now, this doesn’t mean that there are no rules for children’s participation in research, it only means that the rules differ between countries. And as far as I know, none of these rules allows any researcher to involve a child in invasive and risky research under any condition – except perhaps if that research is likely to help the child. In contrast, a so called safeguard clause allows EU Member States to lift the general ban on the use of great apes (chimpanzees, bonobos, orangutans and gorillas) in invasive research “in relation to an unexpected outbreak of a lifethreatening or debilitating clinical condition in human beings” (Directive 2010/63/EU Article 55:2). Or in other words, facing an outbreak of Ebola in Europe, vaccine trials in chimpanzees would be permissible. (Whether this research could actually be done in practice is a different question. For a long time, the only industrialized country to keep chimpanzees for invasive research was the USA, but in 2015 the NIH announced it would no longer fund such research and lab chimps are now being retired into sanctuaries).

Interestingly, before I got around to writing any of this, I came across this paper which proposes that research regulation should protect chimpanzees and in fact all non-human primates (NHPs) in much the same way as it protects human research subjects. The authors argue that with so many important similarities in cognitive, emotional and social capacities, it doesn’t make sense to have different ethical frameworks depending on whether a primate is human or non-human. Therefore, they argue, we should move non-human primates out of the utilitarian framework that is generally applied to animal research ethics and into the deontological framework that applies to human research subjects. In practice, this means that research with non-human primates should respect the principles of beneficence and non-malevolence, or in other words, research should preferably benefit and definitely not harm the research subjects.

The paper is an interesting contribution to the debate and well worth reading, for the ideas and the examples of research that would be acceptable under a deontological framework. The idea that some animals should be given a rights-based protection is not new (it underlies the entire animal rights movement), but the paper contributes a unique discussion of the potential to do biomedical research with NHPs in a way that is compatible with the principles of benevolence, non-maleficience and even autonomy and justice. Unfortunately, I don’t think that the picture they paint is realistic. What can be achieved by studying naturally occurring situations is strongly limited, and I would have appreciated if the authors had been more thorough in their analysis of  what research would be made impossible if changing the ethical framework. On the other hand, if this were a paper about how to protect children in research, nobody would dream of arguing about the important research benefits to be lost if children couldn’t be harmed in research! This observation in itself clearly marks the difference in thinking about research in utilitarian and consequentialist terms versus in deontological terms.

From a pragmatic perspective, taking into account the diversity of opinion on the matter, I don’t foresee a change of framework any time soon for non-human primates in research at large. A change for the great apes is way more likely to happen in the near future. With the phasing out of invasive research in chimpanzees, the only great ape species which really played a role in biomedical research, a full ban may be accepted without much protest. By then, it may be reasonable to ask if chimpanzees enjoy greater protection than children in biomedical research. .

 

 

 

Why the abstract shouldn’t be abstract!

A while ago I had a brief exchange with a friend about the accessibility of research results. Not whether they are clear or understandable – simply whether somebody who’s not in an academic research institution can even get their eyes on them. Often, they can’t. because research is published in academic journals owned by publishers who want to earn money from people’s interest in reading scientific information. When this is the case, all that the common mortal can access is the abstract or summary of the paper.

There is much to be said about ways around it through Open Access publishing. But even a researcher who doesn’t consider themselves to be able to publish OA can do something to make the results accessible – and it isn’t that difficult. Use the abstract!

Here’s an illustrative example of how not to use the abstract. Of the all-in-all 10 000 words available to them, the authors used 94 for the publicly visible abstract, and not surprisingly, we don’t get to learn much about the research through these 94 words. In contrast, this example from the same journal demonstrates how 250 words is enough to clearly describe the research question, the methods and the results.

Open Science in October

Do you think about Open Science? Do you practice Open Science? Do you think Open Science matters? My research group is working on the topic during the month of October, with the aim of formulating an Open Science strategy for the group. We’re doing this because we think it makes sense for us to put Open Science into practice, but we need to work out the best way for us and our research.

We identified the following burning issues:

  • Study preregistration
  • Protocol and methods sharing
  • Data sharing
  • Preprint publication

These are the ones we are interested in but need to know more about in order to be able to practice (or make an informed decision not to practice) them. In addition, we prioritize  open access publishing and social media communication – but we’re already working on this. Although with a permanent backlog, we are uploading papers to the university open repository and we try to keep the group’s Facebook page up to date.

In a month, I hope to be able to report back on this. In the meantime, if you want to learn more about Open Science you may want to look at the FOSTER project.