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.

School holiday animal welfare scientists

Every summer, 16 high school students participating in Universidade Júnior at the University of Porto have the opportunity to learn about animal behaviour and welfare – and practice some of their new knowledge in measuring behaviour and welfare. In the Laboratory Animal Science group at i3S – Institute for Research and Innovation in Health, we receive two groups of 8 students who spend a week each with us. Of course, we teach them a lot of theory – we’re scientists after all! – but we try to do it in as playful a way as possible. And there’s plenty of animals.

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There are direct behaviour observations of zebrafish habitat preference, and observations from video recordings of the behaviour of mice and rats during the light and dark period.

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There is a visit to a dairy farm, where the students perform a simplified WelfareQuality assessment and also potentially get some close-up contact with cows.

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And there is a demonstration of dog training as well as a chance to clicker train one’s colleagues.

For our research group, these are two intense but also very rewarding weeks. It is fantastic to be able to share our knowledge and passion for research into animal behaviour and welfare with 16- and 17-year olds who are as interested in animals as we are. We have been doing this since 2014, and of course we hope that some day we will meet a new colleague who once did Universidade Júnior with us!

Thanks to Sara Capas, Andreia Costa, Ana Maria Valentim and Gabriela Morello for the photos.

Research ethics: why we have separate animal ethics committees

“It doesn’t make sense to have separate research ethics committees for animal and human research subjects” is something I’ve heard more than once the last few months. Behind this statement is a theory-based argument based on that different kinds of research cannot be separated and that there is only one research ethics, and the practice-based question of what happens with a project that is approved by one committee but not by the other.

I disagree with the idea that the best approach is a single committee for ethics review, and I think that as soon as we try to test the arguments in practice, it becomes clear that they work best in theory.

It may be that in an ideal world, there is really only one area of research ethics, where the discussion of all issues of how research interacts with other living beings can take place. But this is not how the ethics field looks today, neither as a research discipline nor as a practical activity. Today there is bioethics, which is closely related to medical ethics, and is about the consequences that research has on human beings. And there is animal research ethics, which in terms of approaches and principles is much closer related to the wider field of animal ethics than to the human focused bioethics. In terms of people who work with these issues, there are two communities which overlap very little. And in terms of the approaches they use and the principles they rely on, they are also distinct.

Of course, if we look at ethics as a subdiscipline of philosophy, there are way more than two schools of thinking. But if we focus on biological/biomedical research ethics as a practical activity with a regulatory function, which is what this post is about, there are really two ways. When the research subjects are humans, the analysis is based on Beauchamp’s and Childress’ four principles of respect for autonomy, beneficience, non-maleficience and justice. When the research subjects are animals, the analysis is based on the 3Rs principle of Replacement, Reduction and Refinement.

But this is not just a matter of principles – there are practical consequences having to do with the expertise you need to work with the different kinds of questions. People who review and give recommendations for research projects with human beings have expertise and practical experience in matters such as informed consent and data protection. People who review and give recommendations for animal research are experts on matters such as anaesthesia and environmental enrichment. These areas of expertise are hardly ever combined in the same people, because they really belong to different background training and professional areas.

Now, what about the practical question of projects which include both research with human and animal subjects? it is true that these projects exist – but it is rather rare for the animal and the human parts to be so intertwined that they actually depend on their respective approval to be successful. The few examples that I have seen are when cells of human origin are transplanted into animals, a technique that is quite common in for example cancer research. And from the practical perspective of an animal ethics committee, the issue can be dealt with pragmatically. We do what is our task as an animal ethics committee and review these projects from the perspective of consequences for the animals – and add one requirement: that the procedure of obtaining the cells and using them for the purpose has been approved by the respective human ethics committee. If there is no such approval, we tell the applicant to come back when the approval is in place.

The final stumbling block for a combined committee is the sheer number of people needed to cover all the expertise. To handle project review well, a committee needs to have sufficient expertise also in the different types of research. Since very little of that expertise overlaps between research with human and research with animal subjects, a joint committee needs to include roughly twice the number of people.

This does not mean that animal and human subjects research committees cannot learn from each other. But that is a different topic.

Openness about animal research – whose responsibility?

On June 21st, the Transparency Agreement on Animal Research was launced in Portugal. The presently 16 signatories of the Portuguese Transparency Agreement agree to:

  • Have a statement concerning animal welfare on the Institution’s website.
  • Link to the Transparency Agreement.
  • Provide adequate information to the media and the general public on the conditions under which animal research is carried out and the results achieved.
  • Develop initiatives that promote greater knowledge and understanding of society on the use of animals in scientific research.
  • Report progress made every year and share experiences.

With this move, Portugal becomes the fourth European country with a formal agreement to communicate more openly about animal research, after the UK, Belgium and Spain. This is a welcome initiative and if it is successful, which I hope, we will move towards a climate of discussion where scientists can speak openly about the fact that they use animals in biomedical as well as fundamental research.

But what this implies in terms of roles and responsibilities is not obvious. That it means that we need to talk about how animals are treated is obvious to me as a researcher in laboratory animal welfare and a professional engaged in a number of institutional measures to promote a responsible use of animals in research, such as review of projects with animals and organization of training for researchers in laboratory animal science. And I’m happy to take on my responsibility in communication and talk about these matters. In fact, I already do this. Whenever asked by media, I comment, I have during nearly a decade regularly written about the issue on the blog Animalogos and I have also written opinion papers in leading newspapers.

When looking up the latter link, to an opionion paper published three years ago together with three colleagues, I realise that we opened with an argument that I personally really don’t think is mine: the usefulness of animal research. Not because I don’t believe that research with animals can provide useful understanding of biological mechanisms, but because I think that this is a message which should be communicated by those who use animals in research to provide such understanding. This is the responsibility of my colleagues who do research in neuroscience, biomaterials, immunology and infection, cell division and cancer.

And here is a real challenge for the official promotors of the inititive, in Portugal the national laboratory animal science organization SPCAL. This organization mainly brings together professionals who are involved in caring for animals and providing advice to researchers using animals. These professionals already take a huge responsibility in working for more responsible research with animals – it is not fair to also give them the responsiblity of communicating why this research is important!