Debates on humanization of human-animal brain chimeras - are we putting the cart before the horses?

Research on human-animal chimeras have elicited alarms and prompted debates. Those involving the generation of chimeric brains, in which human brain cells become anatomically and functionally intertwined with their animal counterparts in varying ratios, either via xenografts or embryonic co-development, have been considered the most problematic. The moral issues stem from a potential for "humanization" of the animal brain, as well as speculative changes to the host animals' consciousness or sentience, with consequential alteration in the animal hosts' moral status. However, critical background knowledge appears to be missing to resolve these debates. Firstly, there is no consensus on animal sentience vis-à-vis that of humans, and no established methodology that would allow a wholesome and objective assessment of changes in animal sentience resulting from the introduction of human brain cells. Knowledge in interspecies comparative neuropsychology that could allow effective demarcation of a state of "humanization" is also lacking. Secondly, moral status as a philosophical construct has no scientific and objective points of reference. Either changes in sentience or humanization effects would remain unclear unless there are some neuroscientific research grounding. For a bioethical stance based on moral status of human-animal brain chimera to make meaningful contributions to regulatory policies, it might first need to be adequately informed by, and with its arguments constructed, in a manner that are factually in line with the science. In may be prudent for approved research projects involving the generation of human-animal brain chimera to have a mandatory component of assessing plausible changes in sentience.

Sentient cells as basic units of tissues, organs and organismal physiology.

Cells evolved some 4 billion years ago, and since then the integrity of the structural and functional continuity of cellular life has been maintained via highly conserved and ancient processes of cell reproduction and division. The plasma membrane as well as all the cytoplasmic structures are reproduced and inherited uninterruptedly by each of the two daughter cells resulting from every cell division. Although our understanding of the evolutionary emergence of the very first cells is obscured by the extremely long timeline since that revolutionary event, the generally accepted position is that the de novo formation of cells is not possible; all present cells are products of other prior cells. This essential biological principle was first discovered by Robert Remak and then effectively coined as Omnis Cellula e Cellula (every cell of the cell) by Rudolf Virchow: all currently living cells have direct structural and functional connections to the very first cells. Based on our previous theoretical analysis, all cells are endowed with individual sentient cognition that guides their individual agency, behaviour and evolution. There is a vital consequence of this new sentient and cognitive view of cells: when cells assemble as functional tissue ecologies and organs within multicellular organisms, including plants, animals and humans, these cellular aggregates display derivative versions of aggregate tissue- and organ-specific sentience and consciousness. This innovative view of the evolution and physiology of all currently living organisms supports a singular principle: all organismal physiology is based on cellular physiology that extends from unicellular roots.

CBC-Clock Theory of Life - Integration of cellular circadian clocks and cellular sentience is essential for cognitive basis of life.

Cellular circadian clocks represent ancient anticipatory systems which co-evolved with the first cells to safeguard their survival. Cyanobacteria represent one of the most ancient cells, having essentially invented photosynthesis together with redox-based cellular circadian clocks some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted in excitable membranes, play important roles, not only in the cellular circadian clocks and in anesthetics-sensitive cellular sentience (awareness of environment), but also in the coupling of single cells into tissues and organs of unitary multicellular organisms. This integration of cellular circadian clocks with cellular basis of sentience is an essential feature of the cognitive CBC-Clock basis of cellular life.

Challenges in farmed insect welfare: Beyond the question of sentience.

The global Insects as Food and Feed (IAFF) industry currently farms over a trillion individual insects a year and is growing rapidly. Intensive animal production systems are known to cause a range of negative affective states in livestock; given the potential scale of the IAFF industry, it is urgent to consider the welfare of the industry's insect livestock. The majority of the literature on farmed insect welfare has focused on: (i) establishing that insect welfare ought to be of concern; or (ii) extending vertebrate welfare frameworks to insects. However, there are many overlooked challenges to studying insect welfare and applying that knowledge in IAFF industry contexts. Here, we briefly review five of these challenges. We end with practical recommendations for the future study of insect welfare.

The Gordon Memorial Lecture: Laying hen welfare.

Preference tests remain a useful tool in the assessment of laying hen welfare and have been used to establish what types of resources and enrichments are most likely to meet the birds' needs. Evidence on the underlying structure of bird preference suggests that hens make stable and reliable choices across time and context. This means that their preferences can also be used as a benchmark in the validation of other welfare indicators. Hens have sophisticated cognitive abilities. They are quick to form associations between events and they are flexible in how they apply their knowledge in different contexts. However, they may not form expectations about the world in the same way as some mammalian species. Limited research in this area to date seems to show that hens judge situations in absolute terms rather than evaluating how a situation may be improving or deteriorating. The proportion of hens housed in cage-free systems is increasing globally, providing birds with greater behavioural freedom. Many of the problems associated with cage-free systems, such as keel bone fractures, mortality and injurious pecking, are slowly reducing due to improved experience and appropriate changes in rearing practices, diet, housing design and alignment of breeding goals. However, much remains to be done. The design and performance of veranda-based systems which provide hens with fresh air and natural light is a promising avenue for future research aimed at optimising hen welfare and improving sustainability.

Human Brain Organoids: Why There Can Be Moral Concerns If They Grow Up in the Lab and Are Transplanted or Destroyed.

Human brain organoids (HBOs) are three-dimensional biological entities grown in the laboratory in order to recapitulate the structure and functions of the adult human brain. They can be taken to be novel living entities for their specific features and uses. As a contribution to the ongoing discussion on the use of HBOs, the authors identify three sets of reasons for moral concern. The first set of reasons regards the potential emergence of sentience/consciousness in HBOs that would endow them with a moral status whose perimeter should be established. The second set of moral concerns has to do with an analogy with artificial womb technology. The technical realization of processes that are typically connected to the physiology of the human body can create a manipulatory and instrumental attitude that can undermine the protection of what is human. The third set concerns the new frontiers of biocomputing and the creation of chimeras. As far as the new frontier of organoid intelligence is concerned, it is the close relationship of humans with new interfaces having biological components capable of mimicking memory and cognition that raises ethical issues. As far as chimeras are concerned, it is the humanization of nonhuman animals that is worthy of close moral scrutiny. A detailed description of these ethical issues is provided to contribute to the construction of a regulative framework that can guide decisions when considering research in the field of HBOs.

Moral Uncertainty and Our Relationships with Unknown Minds.

We are sometimes unsure of the moral status of our relationships with other entities. Recent case studies in this uncertainty include our relationships with artificial agents (robots, assistant AI, etc.), animals, and patients with "locked-in" syndrome. Do these entities have basic moral standing? Could they count as true friends or lovers? What should we do when we do not know the answer to these questions? An influential line of reasoning suggests that, in such cases of moral uncertainty, we need meta-moral decision rules that allow us to either minimize the risks of moral wrongdoing or improve the choice-worthiness of our actions. One particular argument adopted in this literature is the "risk asymmetry argument," which claims that the risks associated with accepting or rejecting some moral facts may be sufficiently asymmetrical as to warrant favoring a particular practical resolution of this uncertainty. Focusing on the case study of artificial beings, this article argues that this is best understood as an ethical-epistemic challenge. The article argues that taking potential risk asymmetries seriously can help resolve disputes about the status of human-AI relationships, at least in practical terms (philosophical debates will, no doubt, continue); however, the resolution depends on a proper, empirically grounded assessment of the risks involved. Being skeptical about basic moral status, but more open to the possibility of meaningful relationships with such entities, may be the most sensible approach to take.

What Do Chimeras Think About?

Non-human animal chimeras, containing human neurological cells, have been created in the laboratory. Despite a great deal of debate, the status of such beings has not been resolved. Under normal definitions, such a being could either be unconventionally human or abnormally animal. Practical investigations in animal sentience, artificial intelligence, and now chimera research, suggest that such beings may be assumed to have no legal rights, so philosophy could provide a different answer. In this vein, therefore, we can ask: What would a chimera, if it could think, think about? Thinking is used to capture the phenomena of a novel, chimeric being perceiving its terrible predicament as no more than a laboratory experiment. The creation of a thinking chimera therefore forces us to reconsider our assumptions about what makes human beings (potentially) unique (and other sentient animals different), because, as such, a chimera's existence bridges our social and legal expectations about definitions of human and animal. Society has often evolved new social norms based on different kinds of (ir)rational contrivances; the imperative of non-contradiction, which is defended here, therefore requires a specific philosophical response to the rights of a thinking chimeric being.

On the Legal Status of Human Cerebral Organoids: Lessons from Animal Law.

This paper will ask whether the legal status presently afforded to nonhuman animals ought to influence regulatory debates concerning human cerebral organoids. The New York Courts recently refused to grant a writ of habeas corpus to Happy the Elephant as she was property rather than a legal person while at the same time accepting that she is a moral patient deserving of rights protection. An undesirable situation has therefore arisen in which the law holds a being with moral status to be incapable of benefitting from legal redress due to their legal status as property.The author argues that this is something that we ought to avoid when designing the regulatory framework which will govern the use of human cerebral organoids. Yet, a difference exists in that, whereas the judges already accept Happy is a moral patient, there is presently no consensus around the moral status of organoids. This paper will consider whether human cerebral organoids have passed the moral threshold of sentience. If they have, or are close to doing so, regulators ought to consider their legal status in advance so as to ensure that adequate limitations are placed on this usage so as to avoid unethical practices.

Sentience and Intrinsic Worth as a Pluralist Foundation for Fundamental Animal Rights.

To date, welfare protections have failed animals. In this context, many animal advocates and scholars have supported recognition of animal rights. Animal rights theory, however, remains underdeveloped. This article contributes to the development of animal rights theory and, in this respect, proposes the utilisation of sentience and intrinsic worth concepts as a pluralist foundation for prospective animal rights. Sentience and intrinsic worth as a conceptual underpinning for animal rights hold clear benefits in that (i) the concepts are already embedded in many legal systems, (ii) sentience would enable the development of animal rights to be built on the established interest theory of rights, and (iii) sentience directly links to the justification of rights as being primarily concerned with the prevention of pain and suffering.

When should we ascribe sentience to animals? A commentary on "Hermit crabs, shells and sentience" (Elwood 2022).

In a new review article, experiments on hermit crab behaviour are discussed in the context of possible animal sentience. Sentience can be defined as the ability to experience feelings such as pleasure or pain but there are also broader definitions that include elements of awareness. Here I suggest that of the different levels of awareness described as components of sentience, only the higher levels (assessment and executive awareness) seem distinct from the basic non-sentient cognitive tasks of gathering, processing and storing information, which are demonstrated by most animals. Studies that attempt to differentiate between basic cognitive functions and higher levels of awareness are rare for most animal taxa, including hermit crabs. Therefore, while results such as those obtained from studies of hermit crab behaviour are compatible with sentience they cannot yet be distinguished from simpler explanations based on basic cognitive functions, which we should prefer for the time-being. Nevertheless, hermit crabs are promising model systems for investigating awareness in animals.

Hermit crabs, shells, and sentience.

Hermit crabs have an intimate relationship with gastropod shells and show numerous activities by which they locate, select, and change shells in different contexts. They gather information about new shells and update information about their existing shells. This involves integration of different sensory modalities, memory-formation, and comparison of the overall value of each shell. Crabs also fight to get shells from other crabs, and again they gather information about the shell qualities and the opponent. Attacking crabs monitor their fight performance, and defenders are influenced by attacker activities, and both crabs are influenced by the gain or loss that might be made by swapping shells. Swapping shells involves the defender being naked for a short period. Leaving a shell also occurs if the shell is experimentally fixed in place or buried in sand or if small electric shocks are applied to the abdomen, and the quality of the current shell is traded-off against escaping possible asphyxiation or the aversive shocks. Hermit crabs show remarkable abilities, involving future planning, with respect to recognizing the shape and size of shells, and how they limit their passage through environmental obstructions. They also assess if shells might become available and wait for that to happen. Groups of crabs arrange themselves in size order so that orderly transfer of shells might occur down a line of crabs. These observations are discussed in the light of complex perceptual and cognitive abilities, and the possibility of sentience and awareness is discussed.

Caution is required when considering sentience in animals: a response to the commentary by Briffa (2022) on "Hermit crabs, shells, and sentience" (Elwood 2022).

My recent review examined the complex and intimate relationship between hermit crabs and the empty gastropod shells upon which they depend for survival. Because shells come with costs as well as benefits, the crabs are highly selective about which ones they prefer to occupy. Thus, a new shell is investigated and the information that is gathered appears to be compared with their existing shell before a decision is made. This is often prolonged and complex. Crabs also fight for shells and again the information that is gathered and used to inform fight decisions is complex. In my review, I consider these and other situations with reference to the possibility of sentience (including awareness). The excellent commentary from Mark Briffa expands on aspects of sentience and invokes the use of Lloyd Morgan's Canon to avoid suggesting complex abilities when simpler explanations would suffice. I agree with this approach. However, I also suggest that when simpler explanations appear not to explain the data, then it is reasonable to consider if more complex mental abilities might be used. I also like Briffa's suggestion that the use of an apparently higher mental faculty might result in a mechanism that is simpler than a large number of apparently simple decisions used to make complex decisions.

The Study That Made Rats Jump for Joy, and Then Killed Them: The Gap between Knowledge and Practice Widens When Scientists Fail to Engage with the Ethical Implications of Their Own Work.

Much contemporary behavioral science stops short of considering the ethical implications of its own findings. This generates a contradiction between methods and discoveries, and hinders translation between updated scientific evidence for animal sentience and corresponding political and legal changes. A recent and particularly illustrative example in rodents is described here.

Why the Epistemic Objection Against Using Sentience as Criterion of Moral Status is Flawed.

According to a common view, sentience is necessary and sufficient for moral status. In other words, whether a being has intrinsic moral relevance is determined by its capacity for conscious experience. The epistemic objection derives from our profound uncertainty about sentience. According to this objection, we cannot use sentience as a criterion to ascribe moral status in practice because we won't know in the foreseeable future which animals and AI systems are sentient while ethical questions regarding the possession of moral status are urgent. Therefore, we need to formulate an alternative criterion. I argue that the epistemic objection is dissolved once one clearly distinguishes between the question what determines moral status and what criterion should be employed in practice to ascribe moral status. Epistemic concerns are irrelevant to the former question and-I will argue-criteria of moral status have inescapably to be based on sentience, if one concedes that sentience determines moral status. It follows that doubts about our epistemic access to sentience cannot be used to motivate an alternative criterion of moral status. If sentience turns out to be unknowable, then moral status is unknowable. However, I briefly advocate against such strong pessimism.

Sentience and Consciousness in Single Cells: How the First Minds Emerged in Unicellular Species.

A reductionistic, bottom-up, cellular-based concept of the origins of sentience and consciousness has been put forward. Because all life is based on cells, any evolutionary theory of the emergence of sentience and consciousness must be grounded in mechanisms that take place in prokaryotes, the simplest unicellular species. It has been posited that subjective awareness is a fundamental property of cellular life. It emerges as an inherent feature of, and contemporaneously with, the very first life-forms. All other varieties of mentation are the result of evolutionary mechanisms based on this singular event. Therefore, all forms of sentience and consciousness evolve from this original instantiation in prokaryotes. It has also been identified that three cellular structures and mechanisms that likely play critical roles here are excitable membranes, oscillating cytoskeletal polymers, and structurally flexible proteins. Finally, basic biophysical principles are proposed to guide those processes that underly the emergence of supracellular sentience from cellular sentience in multicellular organisms.

Biomolecular Basis of Cellular Consciousness via Subcellular Nanobrains.

Cells emerged at the very beginning of life on Earth and, in fact, are coterminous with life. They are enclosed within an excitable plasma membrane, which defines the outside and inside domains via their specific biophysical properties. Unicellular organisms, such as diverse protists and algae, still live a cellular life. However, fungi, plants, and animals evolved a multicellular existence. Recently, we have developed the cellular basis of consciousness (CBC) model, which proposes that all biological awareness, sentience and consciousness are grounded in general cell biology. Here we discuss the biomolecular structures and processes that allow for and maintain this cellular consciousness from an evolutionary perspective.

The hatching of consciousness.

Peter Godfrey-Smith's Metazoa and Joseph LeDoux's The Deep History of Ourselves present radically different big pictures regarding the nature, evolution and distribution of consciousness in animals. In this essay review, I discuss the motivations behind these big pictures and try to steer a course between them.

Causation, Responsibility, and Harm: How the Discursive Shift from Law and Ethics to Social Justice Sealed the Plight of Nonhuman Animals.

Moral and political philosophers no longer condemn harm inflicted on nonhuman animals as self-evidently as they did when animal welfare and animal rights advocacy was at the forefront in the 1980s, and sentience, suffering, species-typical behavior, and personhood were the basic concepts of the discussion. The article shows this by comparing the determination with which societies seek responsibility for human harm to the relative indifference with which law and morality react to nonhuman harm. When harm is inflicted on humans, policies concerning negligence and duty of care and principles such as the 'but for' rule and the doctrine of double effect are easily introduced. When harm is inflicted on nonhumans, this does not happen, at least not any more. As an explanation for the changed situation, the article offers a shift in discussion and its basic terminology. Simple ethical considerations supported the case for nonhuman animals, but many philosophers moved on to debate different views on political justice instead. This allowed the creation of many conflicting views that are justifiable on their own presuppositions. In the absence of a shared foundation, this fragments the discussion, focuses it on humans, and ignores or marginalizes nonhuman animals.

Reflecting on 25 Years of Teaching Animal Law: Is it Time for an International Crime of Animal Ecocide?

2019 marked the 25th anniversary of the introduction of Animal Law to the law degree at Liverpool John Moores University. This article examines changes in the legal protection of animals during this time and the impact this will have on research and scholarship in the law relating to animals. We examine whether the overall international treatment of animals has improved and how far the approach to the Animal Law curriculum should be influenced by the growth in concerns around climate change. In this context, we examine the development of the law of ecocide and the extent to which it addresses concerns around animal welfare across the globe. We suggest that those involved in the development of Animal Law, ethics and policy might usefully engage in a new vision of ecocide, which incorporates a clearer notion of 'animal ecocide'. This new approach would enhance the international and national focus on animals in their own right, would recognise increasing knowledge of animal sentience and would move our responsibilities to them beyond anthropocentric approaches to environmental protection. We argue that the inclusion of a more specific reference to animal ecocide would contribute to the development of Animal Law and would lead to an enhanced relationship between Animal Law and attempts to protect the environment.