Bioengineering the animal or the organ?

This week, researchers in at University of Texas Medical Branch were able to show that they could produce an artificially grown lung and successfully transplant it into a mammal. Lungs were grown in the laboratory from cells from the very same pig into which the organ would later be transplanted. The procedure was tested in 4 pigs, of which one lived for 2 months with a functioning transplanted lung.

Transplantation medicine is not something I know very much about, but from being involved in the ethical discussion of both animal research and gene editing, I come across the question every now and then. To me, there seems to be two routes that are being researched at the moment: engineering animals to make xenotransplantation safer and developing the techniques to grow organs in the laboratory from cells originating in the individual who needs a new organ. The Texas team used the second approach. In the discussion of how to put the genome editing tool CRISPR to best use, xenotransplantation is often mentioned as a worthwhile objective to pursue.

It’s in the nature of research that people work on different applications for a similar purpose – in this case a way to produce organs for transplantation which will relieve transplantation medicine from the reliance on human organ donors. At this point nobody is able to tell which route will take us to the goal first. But from the perspective of the 3Rs and especially Replacement, the artificially-grown-organ approach is much more appealing. Even though animal experiments will be used in the development of the method, once it’s considered safe there will be no more need to use animals. Xenotransplantation on the other hand will mean a continued use of animals, which will be bred and kept for the purpose of providing organs for human transplantation.

Cultural differences of ethological relevance

(There was dancing at the congress dinner. That’s an unwritten ISAE rule and something I fully support. But it left less time for writing, so this morning I will present a shorter reflection rather than a full resume of the 3rd conference day)

This post is not about how applied ethologists differ depending on where they come from or where they work. They don’t, actually, or at least not much, not in a significant way that I have been able to observe during my 25 years as an ISAE member. The kind of work they do may differ, because that’s in part determined by the local context in which they work. Some aspects of animal use differ indeed very little: laboratory animals are housed and used in similar ways across the world and lameness scoring is unfortunately needed for dairy cows most everywhere. But sometimes differences are huge because the way certain practices work is so different.

Yesterday presented two examples from the area of animal production. The photo below shows Victor Abreu de Lima from São Paulo, Brasil and his poster on broiler catchers and their attitudes to animal welfare.

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Catching broilers at the farm to ship them for slaughter used to be something you got anybody who needed to earn some extra money in to do. When I was a teenager, this was something a local football team could get money for a training camp doing. Obviously, having teenagers who know nothing about chickens and who just want to get out of the dark smelly dusty chicken house as quickly as possible isn’t great for animal welfare, This is at least one of the drivers for replacing manual catching with automatic. But in Brazil the development has gone the other way, and catchers are now professionals who – at least in the case of the company Victor and his colleagues work with – have a proper work contract and are trained in how to perform their task. And as you can see from the poster, they know and have a lot to say about the welfare of broilers on the farm and during catching. Whether it’s better for a chicken to be caught by a machine or by a professional handler has not been studied, but it seems quite obvious that professional handlers with this kind of insight makes for better animal welfare than unprepared occasional workers!

The next photo shows Marina von Keyserlingk from British Columbia, Canada presenting work by Jane Stojkov on whether dairy cows sent for auction are actually fit for transport. (The answer is that far too many of them aren’t). This question surprised me, as the only auctions for dairy cows I have experienced are those where a farmer sells their surplus heifers to a farmer who is expanding or improving their herd. But the auction pictured on the photo is one for culled dairy cows intended for slaughter, because that is the route between the dairy farm and the slaughter house in Canada today. And since many cows are culled because of health issues, it is a real problem for animal welfare that these cows need to go through an extra round of transport, housing and showing before they are slaughtered.

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Congress blogging Day 2: ISAE, PEI, Canada

 

(One of my co-workers tweeted that I’m blogging from the conference, and the visitor stats for this rather recently launched blog spiked. Good thing that I keep on waking up at 5 am, since I now apparently have a reputation to keep up. Thank you, Nuno!)

The report from the 2nd conference day will be completely lopsided, since I spent the entire morning in the same session, the one on companion animal welfare (and there were no sessions in the afternoon, as the much missed Wednesday afternoon excursions are back in the program this year). I just went through the program for days 3 and 4, and luckily, the coming days I will get to hear talks on farm animals too. The ISAE conference has two parallel sessions, and as far as possible, I try not to move between sessions more than in the breaks. But the consequence of that is the risk of getting a more narrow focus. Well, looking at my own research portfolio, being too narrow or too focused is hardly something I need to worry about…  The reality is that ISAE covers a lot of animals and a lot of topics, and it is challenging to keep up with it all!

The companion animal session took up all morning, and it was very well chaired by Lee Neil and with a coherent program, often with several talks from the same study., and in the following I will respect that rather than the precise order in which they were given.  The session opened with a longer talk by Karen Overall on Turning off dogs’ brains. Behind that title is the finding that in standard behaviour tests (done to select dogs for further professional training), how reactive a dog is to sounds will fundamentally affect how s/he performs in the test.

Judith Stella and Lynda Mugenda presented two papers from the same study working with dogs at commercial breeders (“puppy mills”) in the US. Lynda’s paper addressed how to refine on-site welfare assessment using the Field Instantaneous Dog Observation (FIDO) scoring, and Judith reported the use of welfare scoring to identify good candidates for reforming of retired breeder dogs.

Conor Goold addressed the predictive validity of the dog behaviour assessment used in the Battersea shelters in the UK, looking at how in-shelter assessment related to post-reforming owner reports of dog behaviour. Nicolas Dollion talked about the dimensions of personality in working dogs, based on 37 years worth of data from the Mira foundation in Quebec.

After Conor’s and Nicolas’  talks on studies involving thousands of dogs, our ambition to get a total of 98 dogs from 7 training schools into a study seemed rather meager, but working with companion dogs and volunteer owners is really a different challenge than that of working with single institutions with thousands of dogs. I was both pleased and a little nervous to be presenting dog behaviour work for the first time in my career, and glad that our study of the effects of aversive- and reward-based training methods on companion dog welfare was received with great interest. The last all of the first part of the session, a systematic literature review on service dogs for epileptic people by Amélie Catala, was also a talk I could relate to with our experience of aiming to do a systematic literature review and finding only a handful of papers. This also seems an appropriate way to end the first half of the morning session, by demonstrating that we really need much more of the kind of well designed observational studies that had just been reported!

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Of course, it’s also important that these good studies are put to good use. The graph above illustrates the effect of the Danish dangerous dog act, as reported by Björn Forkman. A sad example of how political decisions are not necessarily aligned with scientific data, a great example of ISAE humor. Hannah Flint also talked about dog aggression, in this case stranger-directed aggression in companion dogs, and discussed the challenges of drawing conclusions from relations between factors such as training and aggression in a cross-sectional study where cause and effect are not clearly separable.

The three last talks were on cats. From Australia, Grahame Coleman reported on how owners’ attitudes affect how they manage outdoor access for their cats and discussed this in terms of Theory of Planned Behaviour.

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From old-town Onomichi in Japan, where there is a large population of unowned cats which are fed by local residents and visiting tourists, Hajime Tanida talked about water provision and Aira Sea about providing toilets to reduce the general soiling of the area where the cats dwell.

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Congress blogging Day 1 PM: ISAE, PEI, Canada

The afternoon session the first day started with Temple Grandin’s plenary talk. The title captures what Temple Grandin has really spent her entire career doing: Crossing the divide between academic research and practical application of ethology on farms. As always, her talk was an energizing tour-de-force full of practical advice. She started by underlining that people in The Field don’t know that applied ethology exists, and that to reach them you need to simplify, simplify, simplify (not because they are not intelligent but because there is very little time to convey whatever concept). As an example of how to be clear, simple and specific in formulating guidelines: don’t write “sufficient space”, write “enough for all pigs to lie down at the same time”. Equally worth sharing is her final reflections which paraphrased went something like “I’ve spent my entire life designing slaughter houses, now they’re busy developing artificial meat, in 20 years people may be thinking that my work was unethical”. (I hope many of us are making that kind of reflection at least occasionally, because it is an important one. It is also one I hope to be able to explore in a future, ISAE-related project).

In the afternoon parallel session period, I of course followed the laboratory animal science strand. It started in an unusually coherent way, with two talks reporting work on the same cohort of mice, by Aimée Marie Adcock And Emma Nip. Their work is based on housing female mice in trios in either standard or enriched cages

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As the photos show, this study brings back the environmental enrichment methodology that is hardly seen in laboratory animal welfare studies today, the one where the animals are given a radically richer environment, rather than the minimal-improvement-within-what-is-still-standard. Another interesting approach in this study is that the animals were housed in trios of three different strains (DBA, C57Bl6, Ball/c), which since they are distinctly coloured means that individual animals can be followed on videos without the need for individual marking.

The two subsequent talks reported studies done in collaboration with other animal users. Sophie Brajon reported results from our work on perinatal mortality in laboratory mouse breeding, where we followed mice in two different breeding facilities. Brianna Gaskill’s work took up recommendations made a decade ago by Pascalle van Loo for reducing aggression in mice and applied them on mice in a toxicology study. Once this work which is still under analysis, both studies have potential to influence recommendations for housing and managing mice. This may also be true for the last study reported in this session, by Becca Franks on curiosity in zebrafish, because indeed the way this species is kept has very little to do with their natural behaviour.

Curiosity also drove me to take part in the final event of the day, a workshop on Animal Welfare Assessment Contest. I have seen this activity discussed in ISAE since more than a decade, but in all honesty, I never engaged with  this North American concept of competing in how to evaluate animal welfare. It has always seemed rather alien to me: in Europe sports is the only activity we compete in at universities – outside the ongoing silent competition for the best marks of course. In a well organized session we got the taste of a real competition, got to try our hand at evaluating the welfare of working donkeys in two different contexts and watch the impressive performance of students with actual competition experience (Megan La Follette on the photo below).

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Congress blogging Day 1AM: ISAE, PEI, Canada

(This blog post brought to you courtesy of the 4 h time-difference-travelling-west-kind-of-jet-lag that wakes you iup at five in the morning eager to start to DO things!)

The International Society for Applied Ethology is holding its 52nd conference in Prince Edward Island, Canada July 30-August 2 this year. For me personally as a scientist, this is the most important conference and the one I enjoy most – the latter partly thanks to my long and strong engagement with ISAE (attended my first congress in 1994, am finishing my 2nd round of being on its council this year) which means that I know so many people here, but undoubtedly also much because this is such a tremendously good humored congress.

This was evident already in the opening ceremony.  President Bas Rodenburg is clearly not intimidated by how high previous president set the bar for making people crack up laughing during presidential talks. I hope some of the first-time conference attenders really takes up his advice on how to deal with PFAQ – People Frequently Asking Questions!*

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The Wood-Gush Memorial Lecture (the invited lecture of the event, to be given by a prominent contributor to knowledge in applied ethology without actually being an applied ethnologist) this year was given by Stevan Harnad, Professor of cognitive science at Université du Québec à Montréal (UQAM). He addressed “the other mind problem”, the challenge of how we understand what other beings experience. Much of the talk recapitulate what Harnad wrote in his inaugural editorial of the journal Animal Sentience, He also reminded us of Marian Stamp Dawkins very influential paper in another journal edited by Harnad, Behavioral and Brain Science. And, well, if you want the best critical analysis of how to deal with the welfare of other minds, Marian Dawkins is still the author to turn to.

The Wood-Gush lecture was followed by parallel sessions and I chose to stay for the session on Cognition and Emotions. Caroline Lee started with a longer talk On Cognitive evaluation of predictability and controllability and implications for animal welfare. She introduced a framework for welfare assessment based on the concept of predictability/controllability as stress modulators and of positive and negative affect.

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Proposing  to use this framework to evaluate the possible welfare impact of new technologies, in her talk she applied it on the case study of virtual fences for cattle  bringing in actual data from studies of how cattle react to the fence. This work is forthcoming in Frontiers in Veterinary Sciences.

This longer talk was followed by three shorter.  Under the title Understanding the bidirectional relationship of emotional and cognitive systems to measure affective state in the animal, Sebastian McBride discussed the cognitive bias test and possible complementing approaches. His underlying argument is that there is a potential bias in how chronically stressed animals perform in the test, since long term stress exposure can change both action and attention, both crucial factors for test performance. Two talks reporting experimental studies using behaviour and attention in sheep followed, by Matteo Chincarini and Camille Raoult.

* I do remember how these people confused and fascinated me when I was a first time conference participant. And yes, PFAQ seems to be a trait; to the extent that the same people participate they continuou to Frequently Ask Questions. Myself included.

What’s the problem with this photo?

I was asked to comment on what the problem is with the stock photo above. RSPCA did well in pointing out that there is a problem, even though they somehow missed the opportunity to explain what the problem is!

The photo shows a mouse female and her litter. Based on that the pups have some fur but don’t yet have their eyes open, I would guesstimate that they are perhaps a week old. Mice are an altricious species, which means that the young are born in an undeveloped stage and are fully dependent on parental care for basically everything during their first week of life. They do develop very fast, and are ready to leave the nest at about a month of age, and sexually mature just a few weeks later. But at the stage of development in this photo, they aren’t capable of doing very much. The place for such young pups to be is the nest that their mother (or parents, males share the parental care if they can, although under laboratory conditions they may or may not be present) have prepared. That provides them with the thermal microenvironment they need – which needs to be warmer than that of an adult mouse given their poorly developed fur.

Judging from own experience of how long it takes to get a good photo of animals, by the time this photo was taken, the pups were no doubt cold. But that is only part of the problem. Anyone who has seen a professional photo session, or having had their photo taken in a studio, knows that this involves lots of bright light and reflectors. Well, this is precisely the kind of environment neuroscientists use to test anxiety in mice – an open and brightly lit space. Mice are nocturnal animals who spend their lives in tunnels and rarely venture out in the open light, and being forced to be in an environment which in nature would be dangerous is stressful for any mouse. Most likely, it is even more stressful for a female when her rather helpless pups are also exposed in this way.

If you want to learn more about our research in this field. check out the Alive Pup Project. But before you go there, let me just reflect on the different ways of making photos and for which purpose. You will see that in the Alive Pup Project we also show photos of pups taken out of their nest. But these photos were taken when the pups were weighed and inspected as part of a research project aiming to elucidate factors behind pup mortality. This is a big problem in laboratory mouse breeding, and research into the problem requires collecting data. In contrast, it is possible to make nice photos of mice in environments which are less stressful for them the one illustrated above

Still, I need to admit that we have also used stock photos of mice in unnatural environments. We simply did not think. Now we will!

 

Rat tickling and thermography

This summer is one of professional workshops  – to an unusual extent and spanning an unusual broad range of topics.

It started in Amsterdam in early June, with a social lab on Responsible Research and Innovation in the NewHorrizon project. This was nothing I had planned and in fact when the invitation arrived only a couple of weeks before the event, I had to change my plans to make room for it. I couldn’t resist the opportunity to meet new people and learn about something I know is important and I actually work with – the concept of RRI. The workshop was fantastic in all aspects. Indeed I got to know new people and in a very constructive way, as the organisation was impressive. Within half an hour, we were working in pairs of people who had never met before and talking about important experiences and priorities in our professional activities. I took a lot of ideas about how to help people work well together from this event, and hope to be able to apply them in my own teaching and event coordination. Of course I also learned about RRI. And hope to learn even more, since one of the other workshop participants is already booked to come and co-organize a workshop with me in Porto.

A month later I spent a week in Lisbon for the EMERGENCE digital media science communication hackathon. An entire week of crossdisciplinary creativity is too much to even attempt to cover in a paragraph in a blog post, but have a look here for a glimpse of the week and here for a more formal presentation.

The next workshop I’m signed up for is one on a specific research methodology, infrared thermography to measure animal welfare. This is an Animal Welfare Research Network event to be held at Roslin Institute in Scotland in September, and it promises to be very practical and hands-on. I read between the lines in the registration form that participants will leave with their clothes smelling of pigs!

What about rat tickling? This is indeed also a workshop opportunity, as a pre-conference event before the International Society for Applied Ethology congress on Prince Edward Island nest week. However tempting the workshop sounds, it coincides with the meeting of the ISAE council so I will spend the day talking with fellow ethologists instead.