Fight Aging!

You, your self, consists of the slowly shifting structural pattern of matter that holds the data of the mind. That structure is thought to reside in the synapses that connect neurons in the brain, though there is some debate on this topic and final confirmation still lies somewhere in the future. Survival after cold water drowning, in which the brain ceases all activity for a time but nonetheless carries on after rescue, adequately demonstrates that the basis of the mind is physical, not ephemeral, however, no matter where exactly it is to be found in the fine structure of brain tissue. This is important, because it means that an individual is only finally, absolutely dead and gone when that structure is destroyed. A person can be minutes past present definitions of clinical death, but still exist, still be dying in the sense that the structures of the mind are being destroyed by ischemia. Past that span of minutes it gets far more sketchy and unknown as how much of the self remains. That is a hard question to answer absent a definitive location for that data. What if the destruction can be halted, the brain preserved, however?

Preservation of the brain, the self, is the point of the cryonics industry. As soon as possible following death, the brain is cooled by stages and perfused with cryoprotectant. The result is vitrification with minimal ice crystal formation, a method demonstrated to preserve the fine structure of brain tissue, assuming a sufficiently comprehensive perfusion was achieved. There are examples of vitrified and thawed nematode worms retaining memory, and the cryobiology field is working towards reversible vitrification of organs to improve the logistics of organ transplantation and tissue engineering. When a patient is cryopreserved by a cryonics provider, the vitrified body and brain is stored in liquid nitrogen, awaiting a future with sufficiently advanced technology to undertake restoration. The individual is clinically dead, but not gone. The mind still exists, paused, and while that remains true we can envisage future combinations of molecular nanotechnology and regenerative medicine that could achieve a restoration to active life. Will that come to pass? Hopefully so, but nothing is certain. You roll the dice and look for the best odds, just as in any other decision. The odds following cryopreservation are infinitely better than those following burial or cremation. No-one comes back from oblivion.

A potential alternative to cryonics is plastination. This uses chemical fixation at room temperature instead of low-temperature vitrification, halting all biological processes by binding them up in fixative molecules while preserving the original molecular structure of the tissues. The technology needed to restore plastinated tissue is likely to be much more advanced than that needed to restore a vitrified brain: there are many more chemical reactions that need to be undone, molecule by molecule, and at the same time as kick-starting the normal cellular processes. At the present time there is no plastination industry akin to the cryonics industry that preserves people following death, but this may be nothing more than a historical accident. If the founders of the cryonics movement in the 1960s and 1970s had the chemistry background to settle on plastination, then we'd be looking back at decades of increasing experience in that technology instead. As the Brain Preservation Technology Prize contest of recent years illustrated, there isn't any great difference between the two approaches in terms of preservation of fine structure in brain tissue. Both can achieve the goal given a good methodology and absence of complications - and in both cases the burden and the challenge of restoration is placed upon future researchers. Which is fine; preserved patients can wait it out for as long as the preservation organizations continue.

How do we assess the quality of a preservation method, however? The primary methodology at the moment is the use of electron microscopy to assess the small-scale structure of neurons and synapses. It is possible to raise objections to this as a measure of success, but it is a good starting point. If significant disruption is seen here, then there is little point in looking any closer until we have a much better idea as to exactly which structures encode data. Another possible approach is to work with studies in lower species that can be preserved and restored, and assess their cognitive function after the process. That isn't possible for plastination, but has been done for vitrified nematode worms, as I mentioned above. Beyond this, what else can be attempted? In the research linked below, a novel approach is assessed in one of the common forms of plastinated brain tissue. The researchers manage to exercise some of the functionality of the preserved brain cells despite the chemical fixation process. If it can be replicated, this strikes me as a very compelling demonstration, and one that should certainly be expanded upon. I would be most interested to learn whether or not this sort of approach could be attempted in vitrified brain tissue at liquid nitrogen temperature - unfortunately I know far too little about this area of science to even guess at how one would go about such a task, or the degree to which it is possible at that temperature.

When Is the Brain Dead? Living-Like Electrophysiological Responses and Photon Emissions from Applications of Neurotransmitters in Fixed Post-Mortem Human Brains

The fundamental principle that integrates anatomy and physiology can be effectively summarized as "structure dictates function". This means the functional capacities of biological substrata are determined by the chemical composition, geometry, and spatial orientation of structural subcomponents. As the heterogeneity of structure increases within a given organ, so does the functional heterogeneity. Nowhere is this more evident than in the human brain. It can be described as a collection of partially-isolated networks which function in concert to produce consciousness, cognition, and behaviour. It also responds to its multivariate, diversely energetic environment by producing non-isotropic reflections within its micrometer and nanometer spaces. The specific spatial aggregates of these dendritic alterations result in processes that have been collectively described as memory: the representation of experience.

When structures of the brain undergo changes sufficient to terminally disrupt these functional processes and the individual is ultimately observed to lose the capacity to respond to stimuli, the brain is said to be clinically dead. This state has been assumed to be largely irreversible. It should be noted that the specific criteria which must be achieved in order to ascribe death to an individual are not universal and exhibit a significant degree of non-consensus. The precise point beyond which the brain is no longer "living", a threshold which remains unidentified, is perhaps less definite than has been historically assumed. Without life support systems, either endogenously in the form a cardiovascular network or exogenously in the form of mechanical aids, the brain degenerates progressively until full decomposition and dissolution. Complete loss of structure is strongly correlated with the complete loss of function. When the brain is dead and the tissue has lost its structural integrity, the individual is assumed to no longer be represented within what remains of the organ.

If, however, the brain is immersed within certain chemical solutions before degeneration and decomposition, the intricate and multiform structures of the human brain can be preserved for decades or perhaps centuries. The gyri and sulci which define the convex and concave landscapes of the brain's outer surface as well as the cytoarchitectural features of the cerebral cortex remain structurally distinct. The deep nuclei and surrounding tract systems remain fixed in space, unchanging in time. Though structurally intact, the functions of the brain are, however, still considered to be absent. It has been assumed that the chemical microenvironment (e.g., pH, nutrient content, ionic gradients, charge disparities, etc.) of both cells and tissues within the preserved brain must be altered to such a degree to prevent degradation that these spaces no longer represent those which underlie the cellular processes which give rise to normal human cognition and behaviour.

The principle of anatomy and physiology which describes the relationship between structure and function would hold that in the presence of structural integrity so too must there be a functional integrity. If the structure-function relationship is a physical determinant, functional capacities should scale with structural loss and vice versa. Therefore the maintenance of structure subsequent to clinical death by chemical fixation could potentially regain some basic function of the tissue to the extent to which structure and function are intimately related. Here we present lines of evidence that indicate brains preserved and maintained over 20 years in ethanol-formalin-acetic acid (EFA), a chemical fixative, retain basic functions as inferred by microvolt fluctuations and paired photon emissions within the tissue. They are both reliably induced and systematically controlled by the display of electrical and chemical probes which include the basic inhibitory and excitatory neurotransmitters or their precursors. Each of these profiles exhibit dosage-dependence and magnitude dependences that are very similar to those displayed by the living human brain. As neuroscientists we have been taught or have assumed that the fixed human brain is an unresponsive mass of organic residual that has replaced what was once a vital, complex structure that served as the physical substrate for thought, consciousness, and awareness. The results of the present experiments strongly suggest we should at least re-appraise the total validity of that assumption.