To store, perchance to thaw?
The cryonics industry promises to freeze and revive the human brain. Neuroscientist Clive Coen explains why this is wishful thinking.
This article is a preview from the Winter 2016 edition of New Humanist. You can find out more and subscribe here.
Sperm, eggs, embryos, blood vessels, skin – what do they have in common? If they’re frozen, stored and thawed according to the optimal procedures of cryobiology, they all function normally. Cryonics offers the same prospect for a whole human or, at a lower cost, a disembodied brain (Cal Flyn explored the cryonics industry in the Summer 2016 New Humanist). The quality of life as no more than a brain merits separate attention; but if you’re hoping to be revived many years hence, that’s the key organ you’ll want to keep intact. To date, the cells and tissues that can be used after sub-zero storage are either loosely packed or only a few cell layers thick. Those characteristics allow for rapid penetration of the anti-freeze agents that protect against damage from water expansion and ice crystal formation; this means their storage can be accomplished before the natural processes of degeneration have begun. But in the case of human brains, is successful cryonics anything other than wishful thinking?
“The brain is quite simply the most complicated object known”; that’s how I celebrated this unique mass of tissue three decades ago in Functions of the Brain (Oxford University Press, 1985). The phrase was highlighted by Oliver Braddick in Nature (“Inside the workings of the brain”, 1986) and soon achieved meme status. It concerns the quantity of the different components, the quantity of each of those components and the quantity of ways in which the components interact. In practical terms, these quantities are incalculable, not least because discoveries in neuroscience are increasing at an escalating rate: it’s not a science that simplifies.
Given the incomparably complicated nature of the human brain, you’d have to be optimistic to commission a cryonics company to store yours in liquid nitrogen in the hope of eventually being revived. The resurrection procedure is still in development. And we’ll skip over any fatal condition that may be prompting you to take time out waiting for a cure. Let’s focus on possible cracks in the basic premise: that the brain can be stored in liquid nitrogen and then thawed and revived. Most of your body is water. Frozen water expands and forms ice crystals. Such effects can rupture membranes that are tethered within a watery environment. But cells possess a degree of elasticity and you’ve been assured that you’ll be treated with protective agents – including anti-freeze – before being delivered into your own ice age.
The scale of the human brain poses particular problems. The protective solutions, whether pumped into a recently deceased body or just a brain, will take a certain amount of time to saturate all the tissues – there must be no exceptions. The junctions between the cells that line the blood vessels in the brain are especially tight; they form the blood-brain barrier, a feature that protects this vital organ in life and will impede the entry of the cryonics agents after death. Clogged-up or collapsed capillaries will delay local perfusion of those agents until they’ve been ruptured by the pump’s pressure. Further barriers are presented by myelin, the fatty substance that surrounds the neuronal pathways within and between the brain’s hemispheres. Myelin is the distinguishing feature of white matter; its insulating properties enable relatively distant parts of the brain to communicate with one another.
Any successful cryonics exercise must balance the gradual onset of freezing against the gradual entry of the protective agents. Structures furthest from the surface will freeze last and, in most cases, will receive those agents last. Whether or not the post-mortem treatment starts within an hour or so of death, the time course for the complementary processes of infiltration and freezing will take many more hours. Where’s the evidence that the protective agents will have saturated all the white matter and all the cell-dense regions (grey matter) before they’ve been frozen?
Even a minuscule risk would translate into a lot of damage if trillions of components are in play. How much damage would be acceptable? A violin may look fine, but a tiny opening in a seam can make it unplayable. A simple break in a neurone’s projection fibre (axon) will take it out of play – and there will be many such breaks. When advocates of cryonics discuss the prospect of fixing the inevitable damage they wave in the direction of nanotechnology. But that doesn’t tell us much: it’s self-evident that all the repairs would have to be at the nano scale. And this dream might as well be embellished with the word technology. Given that cryonics has a pervasive effect on the brain, instances of damage will be widespread. This differs from the damage caused by a stroke, which is more or less restricted in location; the extent of that damage may determine whether an intact part of the brain can gradually correct some of the impaired functions.
So far we’ve focused on the risks posed by cryonics to the brain’s structure. But it will also jeopardise the neurochemical components: the molecules that enable neurones to thrive and communicate with one another. As acknowledged by its advocates, cryonics leads to the dehydration of cells and tissues. Where’s the evidence that the signalling molecules can be protected from irreversible damage due to local dehydration? Just one category at risk – neurochemicals in synapses – will illustrate the extent of the task. Synapses are the sites through which neurones communicate. The receiving, or postsynaptic, part is known to be associated with around 1,500 different types of protein (see T.J. Ryan and S.G. Grant’s “The origin and evolution of synapses” in Nature Reviews Neuroscience, 2009). What degree of attrition would be acceptable?
Advocates of cryonics like to draw attention to a particular study carried out on rabbit and pig brains. The authors reported an impressive degree of preservation when a particular protective treatment was administered before the temperature was dropped below zero. But the irrelevance of this study to human cryonics is announced in its title: “Aldehyde-Stabilized Cryopreservation”. Aldehydes will undoubtedly preserve structural and signalling proteins; this is achieved by cross-linking – permanently disabling – them. But aldehydes are toxic embalming agents so citing this study to bolster the scientific credibility of cryonics is disingenuous.
Here’s another problem: from the moment of death all the cells in the brain – neurones and their supporting cells – are oxygen-deprived. It’s well established that the neurones in the hippocampus that play essential roles in memory are among the first victims of anoxia. What provisions are taken by cryonics companies to mitigate such effects? Full details of the preparatory procedures are provided in a recent case report from the Alcor Life Extension Foundation. Twenty minutes after the client had been pronounced “legally deceased”, manual chest compression was commenced “which provided circulation for the patient”. This is a fine example of wishful thinking. Where’s the evidence that the manual compression “provided circulation” to this dead man – let alone oxygen to his brain?
These accumulating concerns lead to a key question: before the brain goes into the liquid nitrogen, how much damage has occurred due to the early effects of death plus the cryonics procedures? The biological processes that had been keeping the person alive had always been in a vulnerable state. As Erwin Schrödinger pointed out in 1944 (in What Is Life? The Physical Aspect of the Living Cell, Cambridge University Press), the “order-from-disorder” principle for sustaining life depends on biological systems managing to evade entropy – the decay to thermodynamic equilibrium that is the ultimate fate of any closed system.
The case for cryonics may appear to be supported by his comment: “as zero temperature is approached the molecular disorder ceases to have any bearing on physical events”. But Schrödinger wouldn’t have underestimated the molecular disorder that will inevitably accompany the return to normal body temperature. In addition, tissue sustains damage when blood supply is restored after a period of anoxia; a physiological response known as reperfusion or reoxygenation injury.
Let’s consider just one more problem: at the reviving stage it’s going to be necessary to access and resuscitate all the components simultaneously. Even the first steps towards that objective seem unimaginable. But partial reanimation accompanied by partial necrosis wouldn’t bode well and very few sites in the adult brain are capable of cellular regeneration. Cryonics companies freely admit that there’s work to be done if their faith is to meet with success. But this faith seems misplaced on at least two counts. First, the high probability that brains have already sustained an unacceptable degree of damage before being stored in liquid nitrogen. Second, the infinitesimal prospects of reanimation.
Unlike Pascal’s cash-free wager, signing up for cryonics doesn’t have the appeal of there being nothing to lose. The costs, whether paid in advance instalments or from the individual’s estate, are considerable. And if you want to see your loved ones in the distant future, they’ll need to sign up too, and so on. This is not so much a pyramid scheme as an iceberg scheme. And even if it were possible to bring you back to life, how much cerebral dysfunction would you be prepared to accept? “Ay, there’s the rub,” as Hamlet mused when contemplating his own “sleep of death”.
Clive Coen is a professor of neuroscience at King's College, London