On the Death of a Self-Integrating Organism: A Reply to “A Biophilosophical Approach to the Determination of Brain Death”

Two years ago, an effort to revise the 1981 Uniform Determination of Death Act (UDDA), which defined human death as the complete absence of all functions of the entire brain, was paused indefinitely (Truog and Magnus 2023). This failure to revise the UDDA was not unexpected, given the ongoing and heated debate over the integrity and validity of brain death (BD) or death by neurological criteria. While some bioethicists have suggested that the BD framework should be abandoned altogether, others have proposed that it should be revised to affirm that BD is a social and legal construct that is not equivalent to actual biological death (Russell et al. 2019; Lewis, Bonnie and Pope 2020; Lewis et al. 2019; Omelianchuk et al. 2022; Pennington and Souter 2024). A third camp has called for a better philosophical justification for the BD criteria, along with improved clinical testing to ensure that these BD criteria are met (Sulmasy and DeCock 2023). Clearly, despite the hopeful assertions of some, there is still no consensus for death by neurological criteria today.

To break through this conceptual logjam, Sulmasy and colleagues have pursued the third option by proposing that the BD criteria can be saved if three things are done (Sulmasy et al. 2024). First, they suggest that the philosophical rationale used to justify the BD criteria should be changed to acknowledge that the human body is self-integrated and not integrated by the brain. They then propose that this self-integration is lost when the total functioning of the brain, especially the functioning of the hypothalamus, is lost. Finally, they affirm that medical criteria for BD should be expanded to embrace this reality: Patients should only be declared brain dead if they “irreversibly lack conscious responsiveness, spontaneous respiration drive, and brainstem reflexes, and also have diabetes insipidus” (Sulmasy et al. 2024, 963–964).

In response, in the first part of this paper, I will agree with Sulmasy and his colleagues that the human organism is a self-integrating system. As such, it does not need the brain to integrate itself. However, I will also affirm that it is self-integrating because it is self-organized. Thus, the human organism can be described as a self-organizing system, or more precisely, a self-organizing system of self-organized subsystems. Next, I will interrogate Sulmasy and colleagues’ claim that loss of total brain function, including loss of all hypothalamic function, can trigger the death of a self-integrating organism. I agree, but I also think that there is at least one other combination of systemic organ failures that can trigger the death of a BD patient with residual hypothalamic function, because there are other organs that are also vital for the self-integration of the body. Thus, I affirm that we cannot justify and defend the total BD criteria for death as Sulmasy and his colleagues have attempted to do so without opening ourselves up to other combinations of systemic organ failures that would trigger loss of the inherent capacity to self-integrate: Death by neurological criteria has evolved to death by integrative criteria. Finally, we close with a brief discussion of the impact of Sulmasy and colleagues’ proposal on the practicalities of the contemporary BD debate.

When the President's Commission decided to equate the total loss of the brain with biological death over 40 years ago, it noted that BD patients could not be maintained indefinitely (President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research 1981). According to clinical data available at the time, these patients inevitably move to cardiovascular collapse despite the most aggressive therapy and resuscitative efforts. To explain this imminent physiological collapse of the BD patient, the Commission argued that the brain must be the central integrator of the body because, in its absence, the BD patient cannot stay alive for an extended period. Therefore, the Commission recommended that the total loss of the brain should be equated with biological death because the loss of bodily integration, as the consensus view then held, is the definitive sign of death (Scherz 2022).

In contrast to the President's Commission, after affirming a minor clarification that not every single cell of the brain has to be dead for the brain to be totally brain dead, Sulmasy and his colleagues move on to attest that the human body is self-integrating rather than integrated by one organ: “The second philosophical clarification required to preserve the notion of whole BD is subtle but important. Organisms are not merely entities that can be integrated; they are substantially self-integrating” (Sulmasy et al. 2024, 962). They will then explicitly deny that the brain is the central integrator of the body, proposing instead that it has functions vital for the self-integration of the body: “We are not arguing that the brain is the ‘master integrator’ of the organism, but instead that it is a vital component for embodied self-integration” (Sulmasy et al. 2024, 963). To put it another way, for Sulmasy and his colleagues, the brain does not integrate the body. ¹ Instead, it sustains the body's integration, which the body undertakes itself.

In response, as I have explained elsewhere, I agree that the human brain is not necessary to integrate the body because the body is self-integrating (Austriaco 2002, 2004, 2009, 2016a, 2016b). However, we also have to affirm, as Sulmasy and colleagues have yet to explicitly do, that the body is self-integrating because it is self-organized. Self-organization is a process that brings order out of disorder through the local interactions of its parts rather than through the actions of a controller that oversees the behavior of the parts (Ruiz-Mirazo 2013). Imagine a school of fish in the West Philippine Sea or a murmuration of starlings above the University of Santo Tomas campus. A single individual or group of individuals does not orchestrate the dynamic movements of this group of individuals. Instead, the school or murmuration swirls, dives, and swerves because of the local interactions among the individual fish or birds working together to stay together. The whole pattern emerges simply because each fish or each bird is trying to keep alongside its immediate neighbors. Notice that the school of fish and the murmuration of swallows are self-integrating—the collection of individuals acts as a whole—precisely because they are self-organized.

There is remarkable evidence that biological organisms are self-organizing systems where order is established primarily by local interactions between cells, tissues, and organs (McCusker 2020; Mitchison and Field 2021; Gómez-Gálvez et al. 2021; Xavier da Silveira dos Santos and Liberali 2019; Saha and Galic 2018; Merle et al. 2024). This is especially evident during plant and animal development (Erkurt 2018; Merle et al. 2024; Davidson 2024; Kong, Zhu and Roeder 2024). It is clear, for example, that the human embryo is self-organizing where there is no single master cell or cells that coordinate the emergence of form (Deglincerti et al. 2016). Mammalian limb and digit formation—the developmental emergence of the arms and hands, and legs and feet—is another example of self-organization where local cell–cell interactions within a morphogenetic gradient established by cells at the tip of the limb bud shape the emergence of hands and fingers: The limb bud can develop autonomously into a limb even when it is dissected apart from the rest of the embryo (Tickle 2015; Cooper 2015; Parada et al. 2022). A fully developed living organism can be described as a self-organizing system or a self-organizing system of self-organized subsystems characterized by non-linear interactions between hierarchically arranged and nested components (Palacios et al. 2020).

In sum, I agree with Sulmasy and his colleagues that the human body is self-integrating. However, I have to add that the human being is self-integrating because it is a self-organizing system, like every other living organism. These self-organizing systems lack a single master part that coordinates or controls the behavior of the different parts, which in themselves may be self-organizing subsystems. Decentralized control is shared among the parts of the system that interact with each other as an entangled whole.

We move now to the central argument proffered by Sulmasy and his colleagues. Despite affirming the self-integrating nature of the human organism colleagues, they still believe that the brain has a regulating role in integrating the human body. They explain:

In higher mammals such as human beings, many of the most critical, significant, integrative functions of the organism have become localizable to the brain. Mind-body integration, respiratory integration, and many fundamental homeostatic processes, such as regulation of body temperature, endocrine and autonomic activity, are focal to cerebral networks. When all of these have ceased, the organism can no longer reasonably be construed to be substantially self-integrating, even if many of these functions can (with enormous effort and for a limited time) be artificially sustained. (Sulmasy et al. 2024, 963)

To support this claim, Sulmasy and his colleagues note that the only BD patients who have survived for long periods of time are those who retain some brain function, more specifically, some hypothalamic function: “In fact, a close examination of case reports alleging that the bodies of some ‘chronically brain dead’ patients who were said to have lacked intrinsic hypothalamic function but were capable of persisting for extended periods reveals they actually had relatively intact hypothalamic function” (Sulmasy et al. 2024, 963). Referring to the case of TK who lived for decades after a BD diagnosis, Sulmasy and colleagues conclude: “It was his persistent hypothalamic function that enabled him to remain self-integrated for over 20 years” (Sulmasy et al. 2024, 963). In their view, therefore, BD patients survive only because they have retained enough residual brain function that can serve as “a vital component for embodied self-integration.” Loss of this remaining hypothalamic function, indicated by the emergence of diabetes insipidus, would trigger a loss of embodied self-integration. It would trigger death.

Let me add that Sulmasy and colleagues emphasize that in the context of a BD diagnosis, biological death occurs as soon as hypothalamic function is lost. Because of the brain's role as “a vital component for embodied self-integration,” the emergence of diabetes insipidus means that the BD patient has died, that is, his body has lost its capacity for total self-integration. This loss of the capacity for total self-integration is what is essential: “Moreover, were [long-lived BD patients] to have persisted only because of extrinsic hormonal support, they would not have been truly self-integrating” (Sulmasy et al. 2024, 963).

In response to Sulmasy and his colleagues, I think it is crucial to discern how an organ could be “a vital component of embodied self-integration” without being a central integrator. How does residual hypothalamic activity within the context of a BD diagnosis sustain the self-integration of an organism, and how does its loss trigger the death of the patient? Let us consider the case of a long-lived BD patient, TK (Repertinger et al. 2006; Austriaco 2016b). For most of his two decades as a BD patient, TK appears to have had residual hypothalamic function because he did not have diabetes insipidus. Therefore, functional hypothalamic cells—though no evidence of a hypothalamus or hypothalamic tissue was observed during autopsy (Repertinger et al. 2006)—were able to regulate plasma osmotic changes for 20 years by secreting the hormone arginine-vasopressin (AVP) when needed. When TK lost all residual hypothalamic function and diabetes insipidus emerged, however, the loss of regulated AVP secretion meant that plasma osmotic changes could not be controlled. This destabilized the homeostasis of his body, triggering dysfunction and death in individual cells, tissues, and organs. TK died. Loss of hypothalamic function undercut TK's capacity to self-integrate in the same way that loss of cardiac function would also undermine his self-integration. In both cases, the loss of an organ that is “a vital component for embodied self-integration” would lead to death because it destabilizes the homeostatic balance of the body.

The proposal put forward by Sulmasy and his colleagues that loss of hypothalamic function will trigger the death of a BD patient actually increases the number of possible combinations of criteria for death beyond the existing neurological criteria. Consider: Sulmasy and colleagues propose that the brain is “a vital component for embodied self-integration” because the total loss of the brain would destabilize the body's homeostasis, triggering an inevitable physiological collapse of the system. However, the brain is not the only organ in the body that can play this role in the BD patient. In the same way that the hypothalamus regulates homeostasis through AVP secretion, the adrenal glands above the kidneys also regulate homeostasis through cortisol secretion. Therefore, it could be said that a BD patient with intact hypothalamic function can maintain his self-integration not only because of his residual brain function alone but also because of his residual adrenal function. To see this, think about the BD patient with intact hypothalamic function who experiences the total and irreversible loss of adrenal function. She, too, would lose her capacity to self-integrate. She, too, would die. We know this because, without extrinsic hormonal support in the absence of cortisol, she too would undergo the physiological collapse we observe when BD patients with residual hypothalamic function develop diabetes insipidus.

In summary, Sulmasy and his colleagues have proposed that the total loss of brain function, including loss of hypothalamic function, is biological death because the brain is “a vital component for embodied self-integration.” They write: “[M]any of the most critical, significant, integrative functions of the organism have become localizable to the brain” (Sulmasy et al. 2024, 963). Physiologically, these integrative functions are mediated by the autonomous nervous system and the endocrine system centered in the hypothalamus. Thus, in their view, the loss of the total brain leads to a homeostatic state of the body that is so unstable that the body loses its ability to self-integrate.

However, to say that “many” integrative functions have become localizable to the brain is to acknowledge that there is at least one other fundamental homeostatic process that is not regulated by that organ. As I explained above, there is at least another organ—the pair of adrenal glands—that is also a “vital component for embodied self-integration” because it stabilizes the body's internal environment. As such, given the biophilosophical account articulated by Sulmasy and colleagues, death by neurological criteria has evolved to death by integrative criteria. In other words, any set of criteria that leads to the inherent loss of the body's ability to self-integrate would qualify as bona fide criteria for death. And there appear to be several of these.

Finally, we close with a brief discussion of the impact of Sulmasy and colleagues’ proposal on the practicalities of the BD debate. Recall that they have proposed that medical criteria for BD should be expanded to embrace this reality: Patients should only be declared brain dead if they “irreversibly lack conscious responsiveness, spontaneous respiration drive, and brainstem reflexes, and also have diabetes insipidus” Will revising the neurological criteria for death in this way give us the moral certainty we need to say that we are not violating the dead donor rule when we harvest a vital organ from a BD patient who has met the revised neurological criteria for death?

Unfortunately, I do not think so. Let me explain: At the heart of their argument, Sulmasy and colleagues propose that the only BD patients who can survive for long periods of time are those who retain some brain function, more specifically, some hypothalamic function. The residual hypothalamic function allows them to self-integrate. Thus, it keeps them alive. Therefore, loss of residual hypothalamic function leads to loss of self-integration and, therefore, to death. However, one recent study has indicated that the absence of clinical signs of diabetes insipidus in BD patients may not necessarily be due to residual hypothalamic and pituitary activity, but may be caused by kidney failure in these patients (Varelas et al. 2024). This suggests that some BD patients—maybe TK since no hypothalamic tissue was observed at his autopsy?—were able to survive even without residual hypothalamic function, that is, without any brain function whatsoever. If this is verified, it would indicate that loss of total brain function does not lead to the loss of self-integration and, therefore, to death. It would indicate that patients with loss of total brain function are still alive.