PERSPECTIVES The tragic death of Terri Schiavo, mis- SCIENCE AND SOCIETY used by both ‘right-to-life’ and ‘right-to-die’ activists, recently illustrated to the world the difficulties that surround death in the Death, unconsciousness and the brain vegetative state13–15. Many uneducated commentators have inaccurately referred to Schiavo’s condition as ‘brain dead’ or Steven Laureys ‘neocortical dead’, and her gravestone reads, “Departed This Earth February 25, 1990” Abstract | The concept of death has evolved invention of the positive pressure mechanical — that is, the date on which her brain was as technology has progressed. This has ventilator by Bjorn Ibsen in the 1950s, and damaged (although this was not total, and forced medicine and society to redefine its the widespread use of high-tech intensive she was, therefore, not dead), whereas it was ancient cardiorespiratory centred diagnosis care in the 1960s that cardiac, respiratory and on March 31 2005 that her entire brain died to a neurocentric diagnosis of death. The brain function could be truly dissociated. and her heart irreversibly stopped beating. apparent consensus about the definition of Patients with severe brain damage could now This article has a broad ambit. It discu- death has not yet appeased all controversy. have their heartbeat and systemic circulation sses the medical, philosophical, legal and Ethical, moral and religious concerns provisionally sustained by artificial respira- ethical issues that are involved in the deter- continue to surface and include a prevailing tory support. Such profound unconscious mination of human death. The brain-cen- malaise about possible expansions of states had never been encountered before, tred definition of death has a whole brain, the definition of death to encompass the as, until that time, all such patients had died brainstem and neocortical formulation. At vegetative state or about the feared bias of instantly from apnoea. present, only the two former concepts have formulating criteria so as to facilitate organ The earliest steps towards a neurocentric an accepted medical basis. According to transplantation. definition of death were European5,6. In 1959, the consciousness- or personhood-centred French neurologists Mollaret and Goulon neocortical definition of death, patients in Do we have the right to stop treatment using first discussed the clinical, electrophysiologi- a vegetative state are considered dead. This criteria that pretend to know the boundary cal and ethical issues of what is now known article emphasizes that brain death equals between life and death? as brain death, using the term ‘coma dépassé’ death; focuses on the differences between P. Mollaret and M.Goulon1 (irretrievable coma)1. Unfortunately, their brain death and the vegetative state; argues paper was written in French and remained that the neocortical definition of death can- Only a very bold man, I think, would attempt largely unnoticed by the international com- not be implemented on the basis of reliable to define death. munity. In 1968, the Ad Hoc Committee of anatomical criteria or clinical tests; and H. K. Beecher2 Harvard Medical School, which included briefly discusses the law and ethics of death ten physicians, a theologian, a lawyer and a and the end of life. Throughout history, society and medicine historian of science, published a milestone have struggled with the definition and deter- paper defining death as irreversible coma7. Brain death equals human death mination of death BOX 1. In ancient Egypt The report “opened new areas of law, and Brain death means human death determined and Greece, the heart was thought to create posed new and different problems for theo- by neurological criteria. It is an unfortunate the vital spirits and the absence of a heartbeat logist and ethicist ... it has made physicians term, as it misleadingly suggests that there was regarded as the principal sign of death3. into lawyers, lawyers into physicians, and are two types of death: ‘brain’ death and The first person to consider irreversible both into philosophers”8. Some years later, ‘regular’ death4. There is, however, only one absence of brain function to be equivalent to neuropathological studies showed that dam- type of death, which can be measured in two death was Moses Maimonides (1135–1204), age to the brainstem was critical for brain ways — by cardiorespiratory or neurological the foremost intellectual figure of medieval death9. These findings initiated the concept criteria. This misapprehension might explain Judaism, who argued that the spasmodic of “brainstem death”10 and led UK physicians much of the public and professional confu- jerking observed in decapitated humans did to define brain death as complete, irrevers- sion about brain death. Bernat and colleagues not represent evidence of life as their muscle ible loss of brainstem function11,12: “if the have distinguished three levels of discussion: movements were not indicative of presence of brainstem is dead, the brain is dead, and if the definition or concept of death (a philo- central control4. However, it was not until the the brain is dead, the person is dead”10. sophical matter); the anatomical criteria of NATURE REVIEWS | NEUROSCIENCE VOLUME 6 | NOVEMBER 2005 | 899 PERSPECTIVES Timeline | Medical, philosophical, ethical and legal milestones in death, dying and permanent unconsciousness Fred Plum and Jerome Wada performed the first Nancy Cruzan ruling made no Pope Pius XII ruled that Posner (New York, USA) Japanese heart transplant and legal distinction between Victor Horsley (London) there is no obligation to introduced the term ‘locked was charged with murder. artificial hydration and nutrition published On the Mode of use extraordinary means in syndrome’ to reflect the and other medical treatments Death in Cerebral to prolong life in critically quadriplegia and anarthria Harvard Medical Robert Veatch such as ventilator support, Compression and its ill patients and that it that are brought about by the School Ad Hoc (Georgetown University, First (and only) US and confirmed that these Prevention, which reported the remains for the doctor to disruption of corticospinal Committee defined USA) introduced a Collaborative treatments could be first patients who would now give a definition of the and corticobulbar pathways irreversible coma as a higher brain formulation prospective study withdrawn in patients in an be known as brain dead160. “moment of death”147. in brainstem damage161. new criterion for death7. of death25. on brain death43. irreversible vegetative state150. 1894 1952 1957 1959 1966 1967 1968 1972 1975 1976 1977 1980 1990 1992 Bjorn Ibsen (the ‘father of Mollaret and Goulon Christiaan Barnard Bryan Jennett (Glasgow, Karen Ann Quinlan ruling in Unbalanced BBC University of intensive therapy’) invented (Claude Bernard Hospital, performed the first UK) and Fred Plum (New the USA encourages the television program entitled Pittsburgh, USA, mechanical ventilation Paris, France), coined the human to human York) introduced the term use of living wills and “Transplants — are the protocol for “non- (Copenhagen Kommune term ‘coma dépassé’ and heart transplant (Grote ‘vegetative state’ for ethics committees to donors really dead?” heart-beating Hospital, Denmark). defined death on the basis Schuur, Cape Town, patients with “wakefulness permit the removal of life- alarmed the UK public and donors”48 was of neurological criteria1. South Africa). without awareness”52. sustaining treatments from the number of kidneys established. patients in a permanent donated for transplants vegetative state150. subsequently dropped. death (a philosophical/medical matter); and death. Whole brain and brainstem death are the mutual interaction among all parts26. the practical testing, by way of clinical or both defined as the irreversible cessation of Second, he has presented at least 50 thought- complementary examinations, that death the organism as a whole, but differ in their provoking cases of children and adults with has occurred (a medical matter)16. anatomical interpretation. Because many brain death who were treated aggressively areas of the supratentorial brain (including and had their circulation maintained for The concept of death. At present, the most the neocortex, thalami and basal ganglia) many months or longer30. There have also accepted definition of death is the “perma- cannot be accurately tested for clinical func- been pregnant patients with brain death for nent cessation of the critical functions of the tion in a comatose patient, most bedside tests whom continued intensive care treatment organism as a whole”17. The organism as a for brain death (such as cranial nerve reflexes was requested until the foetus was mature whole is an old concept in theoretical biol- and apnoea testing) directly measure func- enough to be born31–34. The most exceptional ogy18 that refers to its unity and functional tion of the brainstem alone4. The neocortical of such cases was the successful maintenance integrity — not to the simple sum of its formulation of death, which was proposed of a pregnant woman with brain death from parts — and encompasses the concept of an in the early days of the brain death debate25, 17 to 32 weeks of gestation32. These cases organism’s critical system19. Critical func- advocates a fundamentally different concept have been used by Shewmon to show that the tions are those without which the organism of death: the irreversible loss of the capac- neurocentric concept of death