Can they reason? A Utilitarian Perspective on the Neuroethics of Xenotransplantation
Jeremy Bentham, whom some consider to be the father of modern utilitarianism, prophesied that the time would come, “when humanity will extend its mantle over everything which breathes…” In addressing the issue of animal suffering, Bentham posited that the guiding question driving decisions concerning animal suffering should be, Can they suffer?, rather than, Can they reason? or Can they talk?. Since the beginnings of successful organ transplantation, the sourcing of suitable donor organs has proved to be a challenging question, fiscally, medically, and ethically. Recent scientific advances in the field of genetics and cellular biology have made the production of human organs within animal hosts a very real possibility, a development that carries with it a multitude of challenging ethical dilemmas. The purpose of this paper is to analyse these advances specifically within the framework of cognition and perception in human-animal chimera and the ethical ramifications of harvesting organs from such chimera.
Literature review
Proposed as an application of the ability to create human-animal chimeras through the introduction of human PSCs into animals is to provide a means to grow human organs for transplantation. First achieved in murine models in the 1990s (Chen, Lansford, Stewart, Young, & Alt, 1993), and subsequently developed to be effective in large animals (Wu et al., 2017; Wu & Izpisua Belmonte, 2015), this process is termed xenogeneic blastocyst complementation (XBC). As outlined in a recent review article (Oldani, Peloso, Lacotte, Meier, & Toso, 2017), this process goes as follows: 1. Human PSCs are transplanted into an organ-deficient animal blastocyst (created beforehand through the selective gene editing of CRISPR/Cas systems (Wu et al., 2017) in order to ensure only human cells contribute to the generation of the selected organ and avoid later complications upon transplantation (Rashid, Kobayashi, & Nakauchi, 2014)), 2. The chimeric blastocysts are implanted into a surrogate, 3. The offspring are then raised in a controlled environment until the specific organ is of a suitable size for transplantation, 4. The organ is harvested from the chimeric animal and transplanted into the organ recipient.
Many have highlighted the ethical issues that, as with the majority of advances in genetic and biomedical engineering, must be taken into consideration before this process is to be put into practice (Bourret et al., 2016; Eberl & Ballard, 2009; Hermerén, 2015; Piotrowska, 2014). Of those, a few briefly indicated that whole-body chimerism may lead to the issue of human brain cells developing in a host animal. This possibility is due to the fact that chimerization is at best somewhat directable and, without selective targeting through gene-editing of PSCs (Kobayashi, Kato-Itoh, & Nakauchi, 2015), will lead to the spread of human cells throughout the whole organism. One article explored the neuroethical issue in greater depth, although solely in the context of animal research (Capps, 2017). These concerns are well-founded, as research has indicated that the introduction of human PSCs into murine chimeras has led to greater cognitive function.
Within the last decade, a group of researchers effectively introduced human neuronal cells into a mouse model (Muotri, Nakashima, Toni, Sandler, & Gage, 2005). These findings have helped foster more research specifically related to neuroscience in chimeric animal models.
In March 2013, a team of researchers from the University of Rochester Medical Center and the UCLA David Geffen School of Medicine reported their findings on the engraftment of human glial progenitor cells (GPCs) in adult mice (Han et al., 2013). This team introduced human astrocytes into neonatal immune-deficient mice and found, among other things, that the mice developed altogether normally apart from the growth and propagation of human glial cells that maintained their human-specific physiological characteristics throughout the the forebrain, including the hippocampus and cortex. Synaptic plasticity and strengthening of excitatory transmission were significantly increased in the human-mice chimeras as opposed to unengrafted and allografted control groups. Additionally, and most surprisingly, the researchers showed in four tests (auditory fear conditioning, contextual fear conditioning, barnes maze testing, and object-location memory task) that mice engrafted with GPCs were significantly faster at learning than the previously described control groups.
In another recently published study, a group of researchers displayed that PSC transplantation into a rat model of Huntington’s disease successfully attenuated the ill-effects of striatal degeneration and “improved learning and memory function” of the test rats in a six-week comparison study against control littermates (Mu et al., 2014).
The novel developments in XBC, together with the established effects of the introduction of human brain cells into animal models, necessitate a discussion surrounding the neuroethics of chimeric xenotransplantation.
Discussion
In light of the rapidly advancing technologies in the areas of genetics, biotechnology and bioengineering, one area of special interest to bioengineers and other scientists is organ transplantation; an interest necessitated by a system drained of resources. According to statistics published by the Organ Procurement and Transplantation Network, there are 116,469 candidates for organ transplantation in the U.S. on a waiting list as of November 5, 2017 (“Data – OPTN,” n.d.). Additionally, they report that, “on average, 20 people die each day in the U.S. while waiting for a transplant.” It is obvious to many that a source other than donors must be found if progress is to be made in treating those in need. Scientists have proposed and made great advances, as discussed earlier, in developing a method for xenogeneic organ culture. This proposed method is still fraught with difficulties such as limited viability of xenogeneic organs in recipient organisms (Cooper et al., 2017), xenograft rejection by recipient organism immune response (Nottle et al., 2017), and controlling PSC dispersion and differentiation in the host organism (Levine & Grabel, 2017). From an ethics perspective, this answer to the organ crisis is far from suitable.
The issue of dispersion of human cells into the nervous system of animals poses a direct ethical dilemma as the lines between what is human and what is animal become blurred. Bentham, already inclined to argue against experimentation on animals solely because they can suffer, would possibly increase in his opposition to animal suffering if one had to stop at the question, Can they reason? At what point does human consciousness become human? What is it about human thinking that separates us from animals? What rights are afforded to people in vegetative comas with little to no brain function? If a mouse is able to learn more quickly and more effectively as a result of having human glial cells incorporated into its nervous system, does it have a higher level of consciousness than other mice? Should it be afforded a higher ethical status? Certain researchers claim that non-human primates are unsuitable for the proposed XBC because of their similarity to humans (Oldani et al., 2017). Should mice, rats, pigs, or any animal for that matter be excluded then, because of their potential to have something closer to that of a human consciousness? A strict utilitarian would agree, because not only would the animal be capable of suffering, they may also be capable of reason.