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The Animal Ethics of OrganEx

photograph of pig head poking around barn door

As Benjamin Franklin famously wrote in his 1789 letter to physicist Jean-Baptiste Le Roy, “in this world nothing can be said to be certain, except death and taxes.” While it seems nothing can be done about the latter, science has been progressively fighting the former for centuries. Or, at least, challenging when death’s inevitability befalls us.

In a recent paper published in Nature, a team from Yale University claim to have developed a system – dubbed OrganEx – capable of reversing some of death’s effects over an hour after cardiac arrest. If we’re to believe the findings (and there seems to be a good reason to do so), then this team has pushed the boundary separating life from death. Before going further, however, it should be pointed out that the experiment was carried out on pigs and the restored features of life were nothing as grand as consciousness and the capacity for independent living; they were cellular.

Nevertheless, the study’s results may have profound implications for medical practice, especially in end-of-life matters like organ transplantation and donation, palliative care, and assisted dying.

In short, OrganEx was developed from an already existing experimental system called BrainEx. Developed in 2019, BrainEx showed the capacity to preserve the structure and function of cells within a pig’s brain hours after decapitation. OrganEx takes the same principles and applies them to the entire body. It consists of two essential parts. The first is an infusion device attached to the body via the femoral artery and vein. The second part is a complex chemical cocktail that the infusion device circulates through the body, mixed with the recipient’s blood. This concoction consists of amino acids, vitamins, an artificial oxygen carrier, and neurological inhibiting compounds, among other things. An hour after researchers stopped the pig’s heart and withheld medical assistance, the OrganEx system started pumping the perfusate around the pig’s body. After six hours of circulation, tests showed that oxygen had begun reaching multiple bodily tissues and that the pig’s heart had demonstrated limited electricity activity. Additionally, some expected cellular degradation appeared absent. In fact, some cells were metabolizing glucose and building proteins.

In other words, compared to the experiment’s control groups, OrganEx began repairing damaged organs hours after death.

The study’s results are remarkable, and the paper has received significant media attention (many making references to the idea of Zombie Pigs). However, an unease sits at this study’s core and, unfortunately, at the core of many biomedical studies – the use of animals in experiments.

Unlike the BrainEx study, in which researchers acquired the pig’s head from a slaughterhouse, the pigs used in the OrganEx study were slaughtered deliberately for the study’s purposes. Is this ethical? Can we justify the use of these pigs in the OrganEx experiment? I believe a perfectly suitable alternative was overlooked, an alternative that would have meant that the pigs used in the experiment could have continued their lives without being slaughtered – human cadavers.

Within research ethics, there is a widely employed framework known as the 3Rs. Proposed by Russel and Burch in their 1959 book, The Principles of Humane Experimental Technique, these Rs stand for Replacement, Reduction, and Refinement, and researchers should consider each of these principles in order. Replacement refers to substituting animals in research with technological alternatives or simply nothing at all. If it isn’t possible to replace animals, researchers move on to the reduction principle, using as few animals as possible to minimize potential suffering. Finally, if replacement and reduction aren’t possible, researchers should seek to refine their husbandry and experimental methods to reduce suffering and improve welfare. The OrganEx’s study designers seemed to consider such principles, and Yale’s Institutional Animal Care and Use Committee gave comparable advice: “we sought to minimize the animal number and any potential discomfort and suffering.”

I believe, however, that the use of pigs in this experiment breached the first of these principles. The appropriate number of pigs would have been zero, as freshly deceased people would have provided equally effective test subjects.

This might strike some as an odd claim to make. After all, researchers use non-human animals in the preclinical research phase as a buffer before human testing. Bypassing such a precaution and going straight to human research goes against the typical wisdom of research ethics and protocol. However, it is essential to remember that the subject needs to be dead for the OrganEx experiment’s purposes (or at least “dead” according to our current conception of death). That is the experiment’s point, to explore the technology’s posthumous application. As such, research participants cannot be harmed as we typically envision (i.e., allergic reactions, unforeseen side effects, etc.) because they’re already dead.

Death is not an unusual event. It happens to countless people every day. My proposal is that the researchers could have taken advantage of this naturally occurring, potentially suitable research populace but chose to use pigs instead; pigs that they slaughtered deliberately.

So, the question becomes which potential subject is more ethically justifiable: live pigs needing slaughtering to satisfy the experiment’s participation requirements or the bodies of humans who had recently died from natural causes?

All other things being equal, this seems to be a fairly straightforward choice. Living beings deserve more moral consideration than dead ones because the living can experience harm, have a greater claim to dignity, and possess complex internal worlds (pigs especially). The dead lack these things, and while we may attach morally valuable attributes to the deceased, such qualities pale compared to the living. This is true for comparing intra-species (dead human vs. live human) and inter-species (dead human vs. live pig). In short, living pigs deserve more moral consideration than dead humans, and in a research context, if you can use an already dead human instead of slaughtering a live pig, and you subscribe to the principle of reduction, then you should use the human cadaver.

That said, there might be good reasons why the researchers chose to use pigs instead of humans. They do indicate that the BrainEx study focused on a pig brain, and some consistency with that existing work would make sense. I’m unconvinced, however, that this is a compelling enough reason to decide to use pigs in this subsequent study. This is certainly true given that, presumably, the OrganEx’s anticipated application isn’t on pigs but on humans. It would seemingly make sense to align the experiment closely to the anticipated application as early as possible and skip unnecessary research steps.

Ultimately, there are good arguments to use animals for research if doing so helps prevent downstream harmful outcomes (although I don’t necessarily buy them). Nevertheless, if those outcomes can be avoided without using animals, then there is an ethical duty to do so. Preventable harm, including death, should be avoided where possible, which applies to animals as much as it does to humans.

The Ethics of Chimeric Research

microscopic image of human embryos

Recently, various news outlets covered the creation of the first human-monkey chimeras in China. A chimera is an organism whose cells come from two or more species. Researchers managed to develop monkey embryos containing human cells after previous attempts relied on pig and sheep embryos. While this type of research is prohibited in the U.S., the work was legal in China. 

Such projects have been conducted with the hope of developing human organs which can then be transplanted into humans and for conducting research into neurological and psychiatric diseases in humans. Even though such embryos do not progress past one or two weeks of growth, these efforts have been controversial. This is because it is difficult to restrict human cell growth to just one organ. According to Robin Lovell-Badge the concern is that without some way to restrict the contribution of human cells they could contribute to the animal’s central nervous system.

Such scientific endeavors present several ethical issues. These include concerns about animal ethics. For example David Shaw, Wybo Dondorp and Guido de Wert argue that given the limited number of organs for transplant, harvesting organs from human/non-human chimeras is a valid option so long as there is a substantial potential benefit to humans and if there are no reasonable alternatives present. 

Unlike other forms of animal research where the benefits may be less certain, harvesting human organs from a chimera would in most cases save a human life, so there is a large proportional benefit. Also, while there may potentially be other options for saving the life of a human requiring an organ transplant (such as research into artificial organs or changes to public policy requiring that people opt-out of organ donation), those options have not been established. For specific people who will die without an organ transplant there is no established alternative option. Thus, with these two conditions met, Shaw et al. argue that it is permissible to kill chimeras for their organs.  

César Palacios-González has argued that while harvesting organs of a human/pig chimera may be acceptable on such grounds, the case for great-ape/human chimera is more problematic. He argues that from a species-neutral standpoint great apes who possess qualities of self-awareness, complex social structures, and the potential to form rudimentary cultures are “borderline persons.” Because of this, great-ape/human chimeras are deserving of moral protection. 

Killing such animals for their organs would be no more morally justified than killing humans who possess less psychological capacities such as infants, toddlers, and adults with less mental capacities than great apes. Palacios-González suggest that we either accept that it is morally acceptable to kill great apes, great-ape/human chimeras and some human borderline persons for their organs, or we must reject harvesting the organs of any of them. 

While the animal rights argument covers some of the ethical issues involved with human/non-human chimeras, ethicists and philosophers also recognize the distinct ethical concerns presented by chimeric research. One of these concerns is whether it is wrong to cross species boundaries to create part-human beings. Is there some fixed line that distinguishes the human species from other animals, and should this boundary be breached?

According to some, crossing the boundary line of the human species is wrong because it is a challenge to God’s existence, however such arguments will not satisfy those who do not believe in a god. For others, crossing the species boundary is inherently wrong because it is unnatural. There are also those who would argue that is morally wrong because it would create too much moral confusion as we must determine the moral status of human-animal hybrids (for discussion, see Meredith McFadden’s “Moral Standing and Human/Non-human Hybrids”). 

On the other hand, such arguments are difficult to pin down because the concept of species is complicated. For example, according to Jason Robert and Françoise Baylis, “Biologists typically make do with a plurality of species concepts, invoking one or the other depending on the particular explanatory or investigative context.” 

One concept of species holds that species are defined in terms of reproductive isolation. If two populations of creatures do not successfully interbreed, then they belong to two different species. However, this definition only applies to species that reproduce sexually. Another definition considers the lineage of a population of organisms and its continuity over time. Such a definition is more encompassing but also more vague. Operationally it can be very difficult to arrive at a set of traits or qualities that completely distinguishes one species from another.  

The scientific conception of species, therefore, is not fixed. There are many ways to describe species, and it can be very difficult to arrive at a specific and distinctive definition of what makes homo-sapiens a distinct species. Because of this, the notion that it is immoral to cross species boundaries is problematic because it is difficult to define the human species in a fixed way. 

On the other hand, as Robert and Baylis point out, the fact that scientists do not have an account of fixed differences between species does not mean that the ethicist couldn’t employ a fixed account. They explain, “notwithstanding the claim that biologically species are fluid, people believe species identities and boundaries are indeed fixed and in fact make everyday moral decisions on the basis of this belief.” They use the example of race as an analogy; where race is not a biologically useful concept, but it can be a socially useful concept. 

If there are good reasons to adopt fixed notions of species for ethical purposes, then there may be a basis to claim that it is wrong to cross the species boundary, particularly because of the moral confusion it could create. Settling some of these issues will likely require that the public take note of the tension that can exist between a scientific account of something and an ethical account. Should we pursue a more open concept of species and of moral status in line with an experimental approach to these issues, or should we rely on the concept of fixed distinctions when it comes to moral matters. The issue of animal/human chimeras asks us to consider what, ethically, does it mean to be human and what does it mean to be a person?

The Moral Quandary of Testing on Animals

Photo of three rats in a cage with a little red house and food and water available

The topic of testing on animals as a form of scientific research has been contentious for quite some time. In most cases, the discussion tends to focus on whether it is morally permissible to test various products and procedures on animals in order to determine whether they would be safe and beneficial for human use. Animal experimentation is not always conducted simply for the benefit of human beings—sometimes the parties that stand to benefit from the research are other non-human animals, often including other members of the same species as the animals being tested.

Defenders of the practice of testing on animals for the benefit of humans argue that the benefits for humans substantially outweigh the harms incurred by animals. Some argue that our moral obligations extend only to other members of the moral community. Among other things, members of the moral community can recognize the nature of rights and obligations and are capable of being motivated to act on the basis of moral reasons. Non-human animals, because they are not capable of these kinds of reflections, are not members of the moral community. As such, defenders of animals testing argue, they don’t have rights. In response, critics argue that if we only have obligations to beings that can recognize the nature of moral obligations, then we don’t have obligations to very young children or to permanently mentally disabled humans, and this idea is morally indefensible.

Other defenders of animal testing argue that it is both natural and proper for human beings to exercise dominion over animals. These arguments take more than one form. Some people who make this argument are motivated by passages from the Bible. Genesis 1:26 reads, “And God said, Let us make man in our image, after our likeness: and let them have dominion over the fish of the sea, and over the fowl of the air, and over the cattle, and over all the earth, and over every creeping thing that creepeth upon the earth.” Some argue that this passage suggests that humans have divine permission to use animals as they see fit. The use of animals for the benefit of humans seems morally defensible to these people for this reason.

Others argue human dominion over other animals is appropriate because human beings have demonstrated their superiority over non-human animals. We are no different from other animals in the sense that we use our natural skills to climb as high on the food chain as our circumstance permit. As rational creatures, our needs extend farther than the needs of non-human animals. As a result, we can use non-human animals to solve a wider range of problems. We can use them not only for protein, but to make our lives longer, better, more beautiful, and more convenient. Critics of such a view argue that might doesn’t make right. What’s more, our enhanced rational capacities also give us the ability to make moral judgments, and these moral judgments should extend to compassion for the suffering of all living creatures.

Arguments against research on animals also come in a variety of forms. One approach focuses on suffering. Famously, Peter Singer argued that what makes a being deserving of moral consideration is their capacity to suffer. If we treat equal amounts of suffering unequally simply because of the species to which the animal happens to belong, our behavior is speciesist—we are taking seriously considerations that are morally irrelevant. Rights based approaches, like the one argued by Tom Regan point out that non-human animals are subjects of lives. There is something it is like for them to experience the world in the unique way that they do. In light of this, we should recognize that non-human animals have intrinsic value and they should not be used as objects to be manipulated for the benefit of human beings.

How should we assess the situation when the research done on non-human animals is done, not for the benefit of human beings, but for the benefit of other non-human animals? In these cases, one major criticism of testing disappears—researchers can’t be accused of failing to take the interests of non-human animals seriously. After all, concern for the interests of non-human animals is what motivates this research to begin with. Vaccines for rabies, canine parvovirus, distemper, and feline leukemia virus have been developed through the use of animal research. These critical procedures improve and even save the lives of non-human animals. When we engage in a consequentialist assessment of the practice, testing on non-human animals for the benefit of other non-human animals seems justified.

On the other hand, it may be that speciesism is rearing its ugly head again in this case. Consider a parallel case in which research was being conducted for the good of human beings. Imagine that a tremendous amount of good could be done for human beings at large if we tested a particular product on a human being. The testing of this product would cause tremendous physical pain to the human being, and may even cause their death. Presumably, we would not think that it is justified to experiment on the human. The ends do not justify the means.  

One might think that one major difference between the case of testing on humans and the case of testing on animals is that humans are capable of giving consent and animals are not. So, on this view, if we kidnap a human for the purposes of experimenting on her to achieve some greater good, what we have done wrong, is, in part, violating the autonomy of the individual. Animals aren’t capable of giving consent, so it is not possible to violate their autonomy in this way.  

Under the microscope, this way of carving up the situation doesn’t track our ordinary discourse about consent. It is, of course, true, that humans are free to use freely (within limits) certain things that are incapable of giving consent. For example, humans can use grain and stone and so on without fear of violating any important moral principle. In other cases in which consent is not possible, we tend to have very different intuitions. Very young children, for example, aren’t capable of consent, and for that very reason we tend to think it is not morally permissible for us to use them as mere means to our own ends. Beings that are conscious but are incapable of giving consent seem worthy of special protection. So it seems wrong to test on them even if it is for the good of their own species. Is it speciesist to think that the ends can’t justify the means in the case of the unwilling human subject but not in the case of the unwilling non-human animal?

Testing on non-human animals for the sake of other non-human animals also raises other sets of unique moral concerns and questions. What is the proper rank ordering of moral obligations when the stakeholders are abstractions? Imagine that we are considering doing an experiment on Coco the chimpanzee. The experiment that we do on Coco might have implications for future chimpanzees with Coco’s condition. The research might, then, have a beneficial impact for Coco’s species—the species “chimpanzee.” Can the moral obligations that we have to concrete, suffering beings ever be outweighed by obligations that we have to abstractions like “future generations” or “survival of the species”?