Time alone will tell whether the distinctions between the two types of cell death are valid or spurious, and whether the concept of apoptosis will gain wide acceptance. Reality will probably turn out to be a great deal more complex. Meanwhile, one should retain, without overemphasis, the twin visions of cell death—one in which death approaches the cell from the outside and the other in which death starts from within the living core of the cell itself. Clinical death
At the opposite end of the spectrum from cell death lies the death of a human being. It is obvious that the problems of defining human death cannot be resolved in purely biological terms, divorced from all ethical or cultural considerations. This is because there will be repercussions (burial, mourning, inheritance, etc.) from any decisions made, and because the decisions themselves will have to be socially acceptable in a way that does not apply to the fate of cells in tissue culture.
Unless death is defined at least in outline, the decision that a person is “dead” cannot be verified by any amount of scientific investigation. Technical data can never answer purely conceptual questions. Earlier in this article it was suggested that the death of the brain was the necessary and sufficient condition for the death of the individual, but the word death was not given much content beyond the very general definition of “irreversible loss of function.” If one seeks to marry conceptions of death prevalent in the oldest cultures with the most up-to-date observations from intensive care units, one might think of human death as the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. The anatomical basis for such a concept of human death resides in the loss of brain-stem function. Functions of the brain stem
The brain stem is the area at the base of the brain that includes the mesencephalon (midbrain), the pons, and the medulla. It contains the respiratory and vasomotor centres, which are responsible, respectively, for breathing and the maintenance of blood pressure. Most importantly, it also contains the ascending reticular activating system, which plays a crucial role in maintaining alertness (i.e., in generating the capacity for consciousness); small, strategically situated lesions in the medial tegmental portions of the midbrain and rostral pons cause permanent coma. All of the motor outputs from the cerebral hemispheres—for example, those that mediate movement or speech—are routed through the brain stem, as are the sympathetic and parasympathetic efferent nerve fibres responsible for the integrated functioning of the organism as a whole. Most sensory inputs also travel through the brain stem. This part of the brain is, in fact, so tightly packed with important structures that small lesions there often have devastating effects. By testing various brain-stem reflexes, moreover, the functions of the brain stem can be assessed clinically with an ease, thoroughness, and degree of detail not possible for any other part of the central nervous system.
It must be stressed that the capacity for consciousness (an upper brain-stem function) is not the same as the content of consciousness (a function of the cerebral hemispheres); it is, rather, an essential precondition of the latter. If there is no functioning brain stem, there can be no meaningful or integrated activity of the cerebral hemispheres, no cognitive or affective life, no thoughts or feelings, no social interaction with the environment, nothing that might legitimize adding the adjective sapiens (“wise”) to the noun Homo (“man”). The “capacity for consciousness” is perhaps the nearest one can get to giving a biological flavour to the notion of “soul.”
The capacity to breathe is also a brain-stem function, and apnea (respiratory paralysis) is a crucial manifestation of a nonfunctioning lower brain stem. Alone, of course, it does not imply death; patients with bulbar poliomyelitis, who may have apnea of brain-stem origin, are clearly not dead. Although irreversible apnea has no strictly philosophical dimension, it is useful to include it in any concept of death. This is because of its obvious relation to cardiac function—if spontaneous breathing is lost the heart cannot long continue to function—and perhaps because of its cultural associations with the “breath of life.” These aspects are addressed in the later discussion of how death has been envisaged in various cultures. Mechanisms of brain-stem death
From as far back as medical records have been kept, it has been known that patients with severe head injuries or massive intracranial hemorrhage often die as a result of apnea: breathing stops before the heart does. In such cases, the pressure in the main (supratentorial) compartment of the skull becomes so great that brain tissue herniates through the tentorial opening, a bony and fibrous ring in the membrane that separates the spaces containing the cerebral hemispheres and the cerebellum. The brain stem runs through this opening, and a pressure cone formed by the herniated brain tissue may dislocate the brain stem downward and cause irreversible damage by squeezing it from each side. An early manifestation of such an event is a disturbance of consciousness; a late feature is permanent apnea. This was previously nature’s way out.
With the widespread development of intensive care facilities in the 1950s and ’60s, more and more such moribund patients were rushed to specialized units and put on ventilators just before spontaneous breathing ceased. In some cases the effect was dramatic. When a blood clot could be evacuated, the primary brain damage and the pressure cone it had caused might prove reversible. Spontaneous breathing would return. In many cases, however, the massive, structural intracranial pathology was irremediable. The ventilator, which had taken over the functions of the paralyzed respiratory centre, enabled oxygenated blood to be delivered to the heart, which went on beating. Physicians were caught up in a therapeutic dilemma partly of their own making: the heart was pumping blood to a dead brain. Sometimes the intracranial pressure was so high that the blood could not even enter the head. Modern technology was exacting a very high price: the beating-heart cadaver.
Brain-stem death may also arise as an intracranial consequence of extracranial events. The main cause in such cases is circulatory arrest. The usual context is delayed or inadequate cardiopulmonary resuscitation following a heart attack. The intracranial repercussions depend on the duration and severity of impaired blood flow to the head. In the 1930s the British physiologist John Scott Haldane had emphasized that oxygen deprivation “not only stopped the machine, but wrecked the machinery.” Circulatory arrest lasting two or three minutes can cause widespread and irreversible damage to the cerebral hemispheres while sparing the brain stem, which is more resistant to anoxia. Such patients remain in a “persistent vegetative state.” They breathe and swallow spontaneously, grimace in response to pain, and are clinically and electrophysiologically awake, but they show no behavioral evidence of awareness. Their eyes are episodically open (so that the term coma is inappropriate to describe them), but their retained capacity for consciousness is not endowed with any content. Some patients have remained like this for many years. Such patients are not dead, and their prognosis depends in large part on the quality of the care they receive. The discussion of their management occasionally abuts onto controversies about euthanasia and the “right to die.” These issues are quite different from that of the “determination of death,” and failure to distinguish these matters has been the source of great confusion.
If circulatory arrest lasts for more than a few minutes, thebrain stem—including its respiratory centre—will be as severely damaged as the cerebral hemispheres. Both the capacity for consciousness and the capacity to breathe will be irreversibly lost. The individual will then show all the clinical features of a dead brain, even if the heart can be restarted. Evolution of the concept of brain-stem death