by Denis Larrivee & M. Farisco
Background and Thesis: Philosophy of Science,
Metaphysics of Parts, and Privileging the Whole
Can a brain
organoid be considered a whole? Do brain properties confer moral compulsion in
isolation? Can brain fragments acquire normative status from their relation to
the whole brain/individual? These are several of an array of questions emerging
from the intersection of the metaphysical domain of parts and wholes and the
domain wherein the human brain is normatively privileged. Such questions are
uniquely raised by current research into human brain organoids, three-dimensional
tissue culture preparations of human brain fragments, hence parts of whole
brains. Classically, extending backward to Aristotle at least, the metaphysical
question traces its origin to the recognition of the unity and independence of
individual things. This understanding views the universe to be individuated,
composed of entities that are embedded in the framework of space-time.
Definitionally, entities are such because they a) have a unique spatio-temporal
location, 2) are the subject of the predication of properties, and 3) are
distinguished by qualitative properties from all other entities [Esfeld 2004].
Parts thus emerge as a subdomain not coextensive with the entity. This, still
dominant, perspective is of significant contemporary interest in philosophy of
science circles in so far as how physical composition is conceived, where
notions like emergence and reductionism, or the constitution of systems, are
broadly debated across scientific disciplines [Gillett 2016]. For brain
organoid cultures, the metaphysical question intersects with normative issues
due to the privileging accorded to human beings, and, by extension, to their
brains and nervous systems. Aristotelian thinking, for example, denies that a
hand can be so regarded when it no longer functions for the good of the whole
individual. That the view we select on part, property, and whole critically
determines the ethical practice we adopt in organoid use will be argued here.
Figure 1A
Nextbigfuture.com
Figure 1B
Sciencemag.org
Introduction: Scope of Contending Issues
Brain organoids
are a readily available experimental source of neural tissue made from human
pluripotent stem cells (Figure 2A, B). Because they are developed from human
cells they possess a full complement of the human genetic repertoire; they are
expected, therefore, to closely mimic physical properties of the brain’s neural
operation. Their increasing sophistication and wide ranging experimental scope
(Figure 3), including likely attempts to develop higher order properties, raise
the possibility that they will soon pose significant ethical issues.
Which properties, how much these properties resemble those of
humans, and which level of brain operation they reflect are matters typically impinging
on their ethical valuation. However, because they are observed in tissue
fragments, it is uncertain how such normative qualifications may apply.
with Sox (Yamanaka) transcription factors to induce neural differentiation.
Functionalism: Can a Property be Privileged Alone?
Contemporary
notions of brain properties are most often equated with functions [Levin 2018],
where a function denotes a mental capacity. Functionalist models prevail, for
example, in conceptions about the mind, like Extended Mind Theory (EMT), that
equate the reality of the mind with the mind’s functioning Levy 2011], e.g.,
recollection, and that include operations conducted beyond the brain. Hence,
functionalist models challenge the metaphysical reality of ‘wholes’, and so
also value contingency in discrete entities alone. Accordingly, functionalist
models tend to a permissive praxis in organoid use. A classical, individuated approach
human brain, by contrast, views properties as existing only when present in a
source. Properties, in this understanding do not predicate in isolation.
Consistent with this view properties in nature emerge from systemic realities,
like the embodied brain. Indeed, living systems appear to characterize all of
natural reality, and to embrace mental function, which does not exist in their
absence. This suggests that organoids must constitute systemic entities in
their own right, in order to acquire a normative status that would preclude
experimental manipulation.
Integration: Can a Part Acquire Normative Status?
Organoids,
however, are most easily understood as parts of organisms and so possess only
some, but not all, properties that accrue to living systems. This organismal
perspective raises the question of whether organoids can constitute lesser
entities, with quantitatively smaller or qualitatively different subsets of
properties from those of whole organisms. That is, can a human brain organoid
constitute a whole according to criteria used for a human organism? This
question concerns two issues: first, whether a subset of properties constitute
a viable whole, a philosophical issue significant for its use in the context of
death determinations for humans, and second, whether a subset of human
properties can be regarded as human. The first question is anchored in the
particular notion of integration used, like that formulated by the 1984 Swedish
Committee on Death Criteria that is premised on coherency and coordination
[Swedish Committee on Death and Dying 1984]. Clinical ethics for death
determinations conclude that in the absence of coherency and coordination a
human being does not exist. By extension, organoids that are not integrated,
according to this definition, would not exist as integral wholes. Conversely,
should this notion of integration obtain, can the presence of a subset of
properties then distinguish the organoid as human? Classically, the absence of
one or more human properties would distinguish an organoid from a human entity
[Esfeld 2004]; according to this understanding, only a full complement of
human, organismal properties (which predicate from the whole) possess normative
status, a state not achieved in organoids. By either reasoning research on
organoids would be broadly permissible.
Autonomy: Which Properties Confer Normative Status?
Are there
properties which are so distinctive as to be normatively valued? Some, like
self consciousness, or at least sentience, seem so unique as to ethically
preclude intervention. This perspective would suggest that some property
subsets are ethically probative; hence, in these circumstances a classical
understanding of distinct entities with a unique set of properties would appear
inadequate to normatively distinguish an organoid from a human being. In this
case both organoid and individual appear to be qualified by the same normative
distinction; indeed, to be both human. The possession of a partial complement
of higher order human properties seems unlikely, however; rather, higher order
properties appear to occur only in unison. The ‘natural’ evidence suggests, in
fact, that in the evolutionary patrimony living systems are purposed to
autonomous existence [Mossio Moreno 2015], a circumstance requiring all
properties together. Much evidence indicates that this purposing cannot occur
by the nervous system in isolation, but requires a systemic embodied dimension
to elicit them. Indeed, key organismal properties appear to emerge from the
body’s association with the brain to generate higher order activity and to
sustain autonomy [Damasio 2012]. Moreover, a consensus global state that is
self identifying appears to lack sufficient representational content in the
absence of the body, demonstrated, for example, in cases of sensory deprivation
[Wiesel Hubel 1963]. Hence, organoids appear destined to remain parts,
incapable of progressing to human wholes.
Caveats: Cloning and Property Proximity
Nonetheless, the
human being remains specially privileged and the use of a full genetic
complement seems to portend access to avenues of exploitation. Developmental
paradigms, which address the many biological details yet unresolved, have the
potential for manipulation of the whole human, a prospect Kant identified as
morally offensive. Current experimental approaches that approximate cloning
(akin to parthogenesis) [Kao et al 2010] and that initiate developmental
trajectories equivalent to those undertaken for the whole human appear, thus,
to be distinguished from the study of brain parts and will likely require close
ethical oversight. The generation of whole systems, albeit over time, raise the
corollary of property proximity and when a variant is sufficiently different to
no longer be seen as human.
Figure 4: Cloning procedure from induced pluripotent
stem cells.
This seems to suggest that while the ethical terrain of organoids
may be governed by metaphysical principles on parts and wholes, which are revealed
by their expression in the natural world, new insights on the nature of the
whole will likely be required. Concepts like spatiotemporal trajectories,
higher order integration, and integral development appear especially pertinent.
That is, a new conception of the whole, and the relationship of the part to it,
appears to be needed, one that is not merely static, but systemic, ontological,
and dynamic.
Concepts
- The development of ethical guidelines for organoid manipulation is intimately linked to the metaphysical concepts of parts and wholes and their relation to contingent value
- However, a static conception of the whole and how higher order cognitive properties are integrated into it will likely require revision to a new systemic and autonomous account of the nature of integration
- These lacunae may also need addressing by a spatio-temporal dynamic that underpins the metaphysical understanding of the whole.
- Experimental manipulation infringing on such physically instantiated wholes may be deemed probative.
References
Esfeld M (2004). Quantum Entanglement and a Metaphysics of
Relations. Studies Hist Phil Mod Phys 35: 601–617.
Gillet C (2016) Reduction and emergence in science and
philosophy. Cambridge University Press, Cambridge.
Levin J (2018) Functionalism Stanford Encyc Phil
Levy N. (2011) Neuroethics and the Extended Mind. In
Handbook for Neuroethics. Sahakian B, Illes J (eds) Oxford: Oxford University
Press.
Kao et al (2010) Mice cloned from induced pluripotent stem
cells (iPSCs) Biol Reprod 83(2):238-243.
Moreno A, Mossio M
(2015) Biological autonomy: a
philosophical and theoretical inquiry. Springer Publishing, Dordrecht
Wiesel TN, Hubel DH
(1963) Single cell responses in striate
cortex of kittens deprived of vision in one eye. J Neurophys 26:1003-1017
Swedish Committee on Defining
Death (1984) The concept of death.
Summary. Stockholm: Swedish Ministry of Health and Social Affairs.
Damasio A (2012) Self comes to mind: constructing the
conscious brain. Pantheon Books, New York.
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