Tuesday, July 19, 2016

New Frontiers in Animal Research Neuroethics at the Center for Neuroscience and Society

By Tyler M. John

Tyler John is a postbaccalaureate fellow at the National Institutes of Health Department of Bioethics interested in resource allocation, animal ethics, and moral theory. This fall, he will begin a PhD in Philosophy at Rutgers University. 

The opinions expressed are the authors’ own. They do not reflect any position or policy of any U.S. governmental entity, including the National Institutes of Health or the Department of Health and Human Services. 

On June 9-10, I joined a gathering of philosophers, psychologists, veterinarians, and biomedical researchers for the Animal Research Neuroethics Workshop at the Penn Center for Neuroscience and Society. The workshop, organized by neuroethicists Adam Shriver, James Serpell, and Martha Farah, focused on the ethical issues raised by new advances in neuroscience research with non-human animals. Here, researchers from many disciplines came together to share notes from the field and discuss new neuroethics problems. 

Over two days, we discussed problems like, What is the moral status of so-called “brains in dishes”? Is it morally permissible for scientists to cognitively enhance mice, rats, and chimps, giving them advanced cognitive capacities? Is it even conceptually possible to have a mouse model of human depression given the substantial psychological differences between humans and mice? What, more broadly, should we say about the scientific validity and moral permissibility of current neurological research on non-human animals? 

Despite our vast disciplinary diversity and some disagreement about issues in moral theory, participants were very quickly able to bridge disciplinary divides and create broad areas of consensus. We soon found agreement both on significant matters in practical ethics and on areas where greater analysis is needed from neuroscientists and bioethicists. 

Some of our discussion focused on the institution of animal research as a whole, with neuroscience research serving as a sample of the studies that are currently being performed on non-human animals. From the outset, virtually all participants in the workshop agreed that the institution of animal research is in need of serious reform. Participants differed in their degree of pessimism about the institution of animal research and the possibility of reform, but all raised significant concerns. 

For one, most at the workshop seemed to agree that a minimal requirement of ethical research on non-human animals is that the benefits of research projects outweigh the harms. However, as scientists, bioethicists, and veterinarians discussed this, we quickly realized that there is no existing institution that analyzes the costs and benefits of animal research protocols. On the one hand grant-makers ensure that research has expected benefits, and on the other hand Institutional Animal Care and Use Committees (IACUCs) try to mitigate harms to animals. But no one group takes the costs and benefits into account in a comprehensive way. 

Another problem we discovered is that IACUCs rarely have members with sufficient expertise to critique animal research protocols. This makes it difficult for bad protocols to be rejected. 

Image courtesy of Wikipedia
Several other criticisms of mainstream animal research were discussed by biologist Joseph Garner. Scientists and journals should be publishing negative data, he argued, and scientists should stop treating animals like tools or “reagents” and treat them more like patients. Our failure to treat animals like patients produces research projects with far too little variability. As an analogy, imagine that we conducted human subjects research with the low variability we have in, e.g., research on mice. All of our participants would be 42-year-old white men who live in the same town, have the same exercise regimen, are the same height and weight, and have nearly identical genotypes! Clearly this would be problematic. Moreover, many animals who are in labs suffer from anxiety, depression, and social isolation. In addition to this being bad for these animals, it lowers the quality and validity of research performed on them. 

Later, biologist Helena Hogberg explained that researchers working to create alternative, non-animal models for translational research are fighting their battle uphill. The FDA, she argued, uses the mouse model as their “gold standard”, so that new models have to be validated against mouse models in order to gain approval. But this is a mistake, since mouse models are known to be imperfect models of human disease. At present, it would be possible for an alternative model to be better than mouse models and still not gain approval because its results diverge from mouse models. Regulators should instead use human biomarkers as the gold standard for validating alternative research technologies. 

Another reason for this uphill battle is that the FDA does not consider minimizing animal suffering a desideratum for models of human disease. Alternative models must therefore have better predictability than existing models in order to gain widespread adoption, since the fact that they do not harm animals is not relevant from the FDA’s perspective. Some commentators wondered whether the FDA should add animal bioethicists to their staff. Others suggested that the necessity and validity of animal models of each human disease be reviewed every 7-10 years to ensure that research is fruitful. 

The remainder of the workshop focused on new neuroethics questions raised by neurological research on non-human animals. On day one, Kristin Andrews and Martha Farah discussed the idea that research on animals might make some animal non-persons become persons through cognitive enhancement. What if researchers engrafted human neural stem cells into another animal’s developing brain and thereby gave her greater cognition? Would this make her a “person”? Would that matter?

Andrews, a philosopher, argued that this is a fundamentally flawed question, because the notion of a “person” is not well-defined. Instead of carving up the world into persons and non-persons, she argued, we should drop the notion of personhood and focus on what moral and legal implications come with an animal’s having certain capacities like rationality, subjectivity, and relationality. Farah’s talk supported this idea. “Personhood” is not a neurological property, she argued, as no amount of neuroscience can tell us whether someone is a person. And “person” isn’t a particularly useful concept, either. Our ethics should therefore focus on animal behavior, ethology, and structure and function, and not on defining and applying the term “person.”

Program from Animal Research 
Neuroethics workshop
But even if it isn’t useful to talk about persons, questions about the morality of such cognitive enhancement remain. On day two of the workshop, Evan Balaban set the backdrop for this discussion with his research on chimeric chicks. These chicks are crossed with quails so that they have brains that are part-chicken, part-quail, and they sing like quails instead of chickens. Robert Streiffer then commented on the moral significance of creating chimeric animals, focusing on the possibility that cognitively enhancing an animal might change her moral status. 

Streiffer argued that it is morally permissible for an agent to cognitively enhance someone only when and to the extent which her newly-acquired moral status is respected in the future. If, for example, adult dogs and adult humans have different degrees of moral status on account of their different cognitive capacities, we are only permitted to cognitively enhance a dog to develop the cognitive capacities of an adult human if we know that the dog’s higher moral status will be respected after she has developed these greater cognitive capacities. 

Some related questions focused on animal agency. Which non-human animals are moral agents? Are such agents required to follow the same moral norms that you and I are? How should it change our thinking about justice, punishment, and retribution if certain non-human animals are moral agents? When humans experience ego-dystonic motor functioning they find it deeply distressful, disturbing, and shameful. As an example, humans with alien hand syndrome often find their hand performing actions that are opposed to their own agency, which thwart their goals and embarrass them. Would other animals with a lower degree of agency, like mice and fish, face similar kinds of harms from ego-dystonic behavior? If so, how does this bear on the permissibility research that imposes ego-dystonic behavior on these animals? 

At one point, the group discussed new research on “brains in dishes”, or neural networks created in labs used to learn things about the human brain. “How brain-like are these neural networks?” some participants asked, “How brain-like do they have to be before we have to worry about what we do to them?” 

Finally, some discussions throughout the workshop focused on the distinction between affective neuroscience and cognitive neuroscience. For example, participants debated whether translational psychological research is valid only if animals involved in research have the same affective states as humans, and not merely cognitive structures analogous to those which we find in humans. If certain animals do not experience depression just like the depression that is experienced by humans, is it in principle possible to learn about human depression from studying these animals? If so, what are these models able to tell us? 

These discussions at the Animal Neuroethics Workshop make it clear that animal research is a field fraught with unknowns and moral perils. As some participants at the workshop pointed out, it may be legitimate to question the whole enterprise of animal research given our great uncertainty about the permissibility and validity of most invasive animal research projects. We do not, after all, believe that it is permissible to treat other humans in such morally risky ways. But whatever we say about the moral status of animal research in the present day, it is clear that scientists, philosophers, and bioethicists must attend to many questions in animal research neuroethics if we are to bring clarity to this morally opaque project.

*updated on July 21, 2016 at 12:17pm EST.

Want to cite this post?

John, Tyler. (2016). New Frontiers in Animal Research Neuroethics at the Center for Neuroscience and Society. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/07/new-frontiers-in-animal-research_14.html

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