Death. The ultimate inevitability for all living organisms. A fact of life. To be poetic about it, one could say death is more natural than life itself, being the state of the vast majority of all organisms ever to have existed.
The Oxford English dictionary lists death as:
- The action or fact of dying or being killed
- The end of the life of a person or organism
- The state of being dead the permanent ending of vital processes in a cell or tissue
- The personification of the power that destroys life, often represented in art and literature as a skeleton or an old man holding a scythe
- The destruction or permanent end of something a damaging or destructive state of affairs
The third definition is the most relevant with regards to the scientific definition of life, though it probably doesn’t come to mind when thinking about fellow humans or animals. For good reason I suppose - we have emotional attachments. Saying grandma has ceased to function at a cellular level may be a bit heartless. But death is death, and ultimately there’s no dressing it up.
Living organisms have an intrinsic order to the molecules which construct them, as opposed to the molecules being disordered, flowing and flying all over the place like in a liquid or a gas. This ordered system has to be able to take up energy from the environment and utilise it to do work within the system, such as maintain the order (or structure) of the system, to replicate hereditary information and power metabolic processes. Furthermore, all this has to be autonomous. The system has to be able to self-sustain. What is evident from this is that life is not a state of being. Life is a process, or rather a collection of self-preserving processes. A dead organism would no longer be undergoing metabolism, and would no longer be maintaining (or trying to maintain) structural order. In short, cellular function has ceased.
As cast iron and clear cut as this is, it’s only very easy to apply to individual cells as the cell is the fundamental unit of life. It is the most basic thing which can be considered ‘living’. With multicellular organisms (e.g. Us.), the picture becomes a bit more complicated. Within us, as in any of you reading this, the vast majority of the cells which compose you should meet the above criteria, hence they are living cells. However, some won’t. When we break ourselves down to our basic units, the picture is a lot different to what we perceive when we look at a multicellular organism as a whole.
Additional criteria are added for multicellular organisms. Bonelli et al 2009 reduced these quite nicely; There has to be indivisibility of the mass of cells. Like, you can’t chop off your arm and that arm buggers off to live independently. The system has to be inherently dynamic - showing signs of mass metabolism and growth. There has to be integration within the organism - cells working together form sub systems (organs) which cannot function autonomously on their own, and must integrate with other systems. All this must be coordinated (In mammals and birds this is achieved by the nervous and endocrine systems). This all comes together to form a complete organism. So we have dynamics, integration, completion and coordination. The underlying concept with the cells of a multicellular organism is unity. They strive for the common cause of the whole. Like, cellular communism or something.
The two criteria for death in the clinical setting are circulatory death and neurological death. Circulatory death occurs when the heart irreversibly stops beating and the pulse (as detected from arteries) is abolished for upwards of 2 minutes. The key word here is irreversibly, as we have the technology to restart the heart. When the heart stops, oxygen ceases to be transported around the body and cells can no longer power their metabolic needs, so they stop functioning. Within the cells, ionic imbalances occur, toxins accumulate, water begins to diffuse freely along concentration gradients and general cellular structural integrity is compromised. As a result, the organs constructed by these cells stop working. In this way, stoppage of the heart leads to neurological death. Circulation must have ceased for some time before neurological death can be assumed, as the brain can survive for a very limited time upon cessation of cardiac function.
With the termination of brain function, there is absolute neurological death - or brain death. All of the properties which we deem to give us our ‘selves’ or our humanity is lost. Irreversible, global brain death means no more consciousness, no more ‘self’, no more thoughts, no more regulation of the rest of the body. The brain is no longer the electrically, chemically, physiologically, metabolically active organic computer, but is reduced to little more than a jelly like mass of inactive neurons encased within an inert bony cocoon.
To be declared brain dead, a patient must meet the following criteria:
- The patient must be demonstrated to be in a coma
- The cause of the coma must be known and evidenced
- Doctors have eliminated confounding factors which can transiently alter brain functionality, these include hypothermia, drug usage and hormonal imbalances
- The absence of reflexes mediated by the brain stem, like the dilation of pupils in response to light
- No movement (kinda obvious)
- Absence of autonomous breathing (apnoea)
- Confirm above tests with repeat tests up to three days after initial assessment
Brain death exists as a criterion for death as machines can artificially sustain breathing (mechanical ventilation) and circulation - but can’t do the same for the complex function of the central nervous system.
The crucial part of the brain responsible for maintaining the life of a complex animal is the brain stem. This is the oldest, most evolutionarily primitive part of the brain which we humans share with reptiles, birds, amphibians and the rest of the mammals. It is the neurological bridge between the brain and the rest of the body. The brain stem is responsible for controlling and regulating basic life processes, including sleep, heartbeat, breathing and blood vessel dynamics. Brain stem damage leads to rapid death.
Location of forebrain and brainstem
The thing is, even in the absence of neural inputs from the brain (say, in the event of absolute brain death, brain stem and all) the heart can beat. The heart is what is known as a ‘myogenic organ’. It generates its own contractions, however unregulated by the brain. With mechanical ventilation, a brain dead patient can remain technically living for years. Various biological functions have been observed to carry on as usual following brain death in mechanically ventilated patients. Such functions include the healing of wounds and the development and successful delivery of a baby.
Organ transplantation complicates the picture further. Using organs from cases such as these will probably give the freshest, best quality organs for transplantation - but at the same time the organ extraction becomes the actual cause of death for the person. The practice of using brain dead patients as donors is practiced widely in the developed world. Such donors are known as heart-beating donors, as their hearts may still be beating at the time of organ extraction. The idea here is that as the patient is brain dead, they are effectively dead and open for pre-consented organ harvesting. This is a very controversial topic in the medical community as the diagnosis of brain death makes assumptions about the patient’s state of consciousness. Some key forebrain structures in brain dead patients may still be intact. Such structures may be deep brain structures, as thus difficult to test for functionality.
Recent studies into the electrical activity of the brains of seemingly brain dead patients (electrophysiological studies, to use the correct term) have observed some electrical activity in response to auditory and tactile stimuli. Some brain dead beating-heart donors have been observed to exhibit the visceral responses (via observation of the response of blood vessel dynamics) and hormonal responses typical of those caused in response to perceived pain. This doesn’t say anything about the donor perceiving pain, but shows some level of centrally mediated processing of what would be perceived as pain. Additionally, a paper published in the journal, Neurology by Wijdicks and Pfeifer in 2008 on autopsy studies of brain dead patients showed that the brain stem appeared to be intact at the gross anatomical scale, and at the cellular scale in 60% of beating-heart donor cases. This may have implications for their actual conscious state at the time of organ extraction, and also for the reversibility of the donors initial ‘brain death’.
However, when we go right back to the initial criteria for multicellular life, brain death does indeed disrupt the unity and coordination of the organism. Furthermore seemingly structural integrity of a brain structure doesn’t necessarily mean it is functionally stable. Cellular chemistry may be upset, or brain stem input and outputs may be disrupted.
So what of organ donation? If heart beat has indeed stopped for any period of time exceeding the 1 hour mark, there is no real medical controversy concerning organ donation. As long as the organs are in good condition and aren’t rejected by the recipient, s’all good. There’s no worry about the donor, they had no more use for the organs anyway. With apparent brain death, we enter a shady, fuzzy region of science and medicine. I guess the reason for the controversy here is simply due to a lack of understanding. Neuroscience research has undergone an explosion in recent times, but we’re still in the early stages of discerning how the brain precisely works. We have a very good understanding of many aspects of brain function but there are still fathoms of uncovered information hidden within the jelly of sulci and gyri that we call our brain.
Death is a complex issue at the scientific and medical level, and this complexity is amplified when we bring it to the table of general society because so many people have such strong feelings about death. Indeed, it is ingrained within the very essence of the biology of all living organisms to want to evade death. With humans, this is never more prominently expressed than in our thoughts. Many of us fear death. Others have stories and ideas of what happens after death, to make the actual event not feel so bad. What makes subjects such as brain death so perplexing is that in the laboratory and the clinic, human death is seen as a single and final event. Someone can’t be half-dead. This is down to our fundamental biology. We may be composed of trillions of individual living cells, but the cells are units of a single organism. Ultimately, they function as a mega society of specialised units, to preserve a basic genome. In this preservation of the genome, we get our organs, our capacity to think and communicate, our capacity to reproduce. Our sociable cells, in both the singular and organismal sense, live together and ultimately, when our times comes, whichever ones are left - will die together.