The conventional view is that humans and other creatures around us live between periods of waking and sleeping. But it is not true. Many have mastered the art of hibernating, which allows them to spend quite a lot of their life in a mysterious state of suspended animation – sometimes more than half of it. What is hibernation, and is it something that humans might be capable of?
At the dawn of scientific enquiry into hibernation (from the Latin hibernus, pertaining to winter) in the mid-19th century, it was defined by Peter A Browne in an 1847 tract as ‘a natural, temporary, intermediate state, between life and death; into which some animals sink, owing to an excess of heat, or of cold, or of drought, or want of oxygen’. That’s a good first approximation. Now we know that – from dormice and bears, to hedgehogs, ground squirrels, bats and even tropical primates – hibernation is a very common phenomenon, found among representatives of at least seven different orders of mammals. It appears in many forms, which makes it difficult to define unequivocally, let alone imagine what it might look like in humans. As another early study points out: ‘we do not find that any two animals, however closely allied, hibernate in precisely the same manner, nor do individuals of the same species always hibernate alike’.
Nevertheless, there is a cluster of features typical of hibernation. The most parsimonious description would include reference to a controlled reduction in metabolism, reflected in a slowing down of many physiological and biochemical processes in the body. In sci-fi movies, hibernating humans are often depicted lying in pods, completely immobile and seemingly unconscious, and it is implied that their body temperature is very low – hence it is often called ‘cryosleep’ or something similar. Any mention of how exactly human hibernation is achieved in those conditions, or what triggers ‘awakenings’ from hibernation, is conveniently avoided, as if that were a trivial matter not deserving attention.
It could be forgivable to skip explaining how something as exotic as human hibernation happens. But it is sobering to think that sleep – a state so familiar to all of us, one we are perfectly capable of, on a daily basis – also remains a mystery. I am a sleep neuroscientist, and the focus of my laboratory is the origin and fundamental biology of sleep. I am convinced that sleep can be fully understood only when it is considered not in isolation but in juxtaposition with other states of being, such as hibernation. Yet research is still at a basic stage and there are so many things we don’t know about this aspect of life. How, for example, can we seriously talk about hibernation in humans, when it is a condition we also do not fully comprehend in other animals? And how can we understand sleep if we can’t clearly separate it from hibernation?
The revival of interest in hibernation in general, and human hibernation in particular, comes at the right time. The genre of science fiction is about imagining and predicting practical solutions for real-life problems when they cannot be solved with existing means. When the world is facing acute problems at a planetary scale, including climate change, technogenic disasters, wars, incurable disease, pandemics and mental health crises, and we are grappling with perennial questions, such as how to attain immortality (or at least extend high-quality life considerably), solve the mystery of consciousness or reach the far corners of the Universe, hibernation emerges as a potential opportunity, if not the only hope. From clinical applications to space travel, scientists, entrepreneurs, governmental agencies and even writers and artists turn to hibernation as a possible solution for our problems, those desires and anxieties we are unable to tackle with more down-to-earth approaches – or, at least, as a way to sleep through them and wake up when things are going better.
Scientists now agree that hibernation can be of two kinds – a seasonal, multiday profound suppression of metabolism, often lasting for months and occupying a good portion of an animal’s life, or else its shorter and milder form, a so-called daily torpor. The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is one typical example of a seasonal hibernator. When they perceive early signs of winter approaching, these squirrels gain weight and build long burrows in the ground where they courageously descend sometime in October, not to see light again until the following March, at least. Remarkably, the body temperature of these animals during hibernation can fall to sub-zero values, and heartbeats and respiration decrease to a tiny fraction of their normal rates. Not surprising, then, that hibernation has been described as a state in between life and death.
Hibernation epitomises what harmony with nature is about
One of the first lab studies of another ‘true’ hibernator, the Syrian hamster (Mesocricetus auratus), reports that, in preparation for hibernation, the animals built a nest that ‘was almost invariably a carefully made affair, so constructed that only the arched back of the animal appeared above the shavings’; then they ‘curled in a tight ball, with the nose tucked beneath the tail’. Their oxygen consumption and temperature would drop concurrently during the process of entering hibernation, reaching their minimal values 3-4 hours later. Djungarian hamsters (Phodopus sungorus), originating from southwest Siberia and northeast Kazakhstan, are instead an example of daily torpidators. When kept at about 6°C ambient temperature, the pelage, or fur, of these animals changes from grey-brown to white, and their body temperature falls to about 20°C; these bouts of so-called ‘daily torpor’ typically last for only a few hours.
Hibernation epitomises what harmony with nature is about – it is defined, by and large, by the amount and rate of exchange of matter, energy and information between inside and outside. Among the key triggers for preparing to enter and entering the state of hibernation are shortage, actual or perceived, of food and light. In response to a shortening day, some animals lose weight and others accumulate food stores, hiding from greedy competitors in secret places outside, or creating energy reserves within their own body – both to be consumed sparingly over the winter. They have to be very precise about this, as emerging too early from hibernation to seek more food means they may freeze or starve to death.
To test how animals deal with energy demands, scientists designed what they called a ‘work for food’ experimental protocol, where laboratory mice were trained to run on a wheel to earn morsels of food, one at a time. Animals kept up with the task well, but only to a certain point. When the experimenters made the task too demanding, requiring too great an effort, mice made a clever decision: instead of working, they chose to enter a state of torpor. Slowing down appeared to be a more economical strategy, and one that increased their chances of survival.
Sometimes, real-life adversity inadvertently becomes part of the experimental design, as in the work of Elsie Proctor, who undertook her study on hedgehogs during three winters before and after the Second World War. She argued that: ‘In pre-war days the feeding of these animals was less difficult (we used milk and eggs),’ which allowed them to investigate ‘whether an adequate supply of fresh food would delay hibernation’. This was before it was discovered that hedgehogs are in fact lactose intolerant, and therefore feeding them with milk is not recommended, but, lo and behold, the better-nourished animals in this study were still able to survive longer and harsher winters by entering into a longer and deeper torpor. The existing theory is that there is some sort of metabolic clock that monitors the energy status of the body, creating a signal that is then integrated with relevant environmental factors, such as temperature and light. When the time is right, the programme of entering into hibernation or returning from it gets put into motion. Clearly, the system must be very flexible, but it also makes it very fragile. The adaptation that was emerging over millennia appears to lag behind the rapid transformation of Earth as a result of human evolution and the development of new and disruptive technologies. It is probably just a question of time before some species stop hibernating altogether.
Did our ancestors use hibernation to survive through the winter when it was cold outside or food supplies dwindled? Or is the entire notion of hibernation related to winter misconstrued, and we need a new and fresh perspective? As we know, there are tropical lemurs that can hibernate at high body temperatures, which suggests that being related to winter is a contingent and unimportant feature of a much broader phenomenon than the name suggests. Scientists now agree that animals hibernate not only to save energy or overwinter cold seasons, but as a way to deal with other environmental calamities. This may include wildfires, heatwaves, storms and perhaps even natural disasters on a cosmic scale, such as the meteorite collisions with Earth that wiped out the dinosaurs but spared small primitive mammals that could well have survived thanks to their gift of hibernating.
Paradoxically, it appears that we are too smart and technologically advanced to hibernate
The applications of human hibernation in sci-fi were many and varied too – from time travel and protection from adverse conditions associated with space travel (eg, surviving extreme acceleration) to economic and practical benefits (eg, reduced need for oxygen and supplies for long-haul interplanetary journeys) to more exotic applications (eg, a form of bioweapon to freeze the enemy in time to temporarily incapacitate them). Animals use hibernation for many of the same reasons. Some species enter hibernation before winter starts and return ‘back’ in the spring. Although they are experts in overwintering, and all individuals of those species must have done it since the dawn of time, they may not even know that winter exists. Hibernation enables them to time travel, to transcend time. Hibernating animals do not lose time, they gain time, and, not surprisingly, growing evidence points to an intriguing association between the ability to hibernate and longevity.
While many animals have mastered the ability to enter torpor, it’s something that eludes us humans. Curiously, despite decades of research, human hibernation remains among the few questions that still belong to both science and science fiction. Is there something special about our nature that prevents us from hibernating? Will we ever know what it is like to hibernate? Clearly, being in torpor and being outside of it corresponds to states that are worlds apart. In our daily life, we are trapped within a very narrow range of physiological parameters, and rarely venture into other dimensions of existence, apart from sleep. This does not suggest, though, that this is all we have. On the contrary, humans have always been remarkably creative and imaginative with respect to changing their state of body and state of mind, for example by taking mind-altering drugs, entering a state of deep meditation, or even willingly changing metabolic rates. While we could possibly find a way to enter hibernation or a similar state, we do not have an immediate or urgent need to do so, as we have developed, and perfected, other ways to deal with adversities. We can make fire and electricity, can build shelters and manufacture warm clothing, get food easily, and spend tremendous amounts of energy derived from outside sources to preserve our own limited supply. Paradoxically, it appears that we are too smart and technologically advanced to hibernate – something other creatures we consider inferior just take for granted.
The possibility of hibernation in humans has always captivated us; we badly want it to be possible, and mentions of human hibernation or suspended animation of different kinds are ubiquitous in the sci-fi genre – from Mary Shelley’s novel Frankenstein (1818) and Vladimir Mayakovsky’s play The Bedbug (1929) to more recent novels like Liu Cixin’s The Three-Body Problem (2008) or Hibernaculum (2023) by Anthony Doyle.
In the domain of scientific literature, there are descriptions of well-documented, though ill-conceived, attempts to induce hibernation in humans. A search for ‘artificial hibernation’ on PubMed – the largest database of biomedical and life sciences work – reveals a peculiar surge in the number of publications starting from the early 1950s and fading around 10 years later. One person behind this effort was the French surgeon Henri Laborit, who was looking for ways to help his patients survive traumatic shock and was inspired by the idea that animals appear to be protected while in the state of hypometabolism. Hibernation therapy, or simply hibernotherapy as the approach has been dubbed, was aimed at inducing a profound inhibition of the autonomic nervous system, to keep the response to injury at bay, as a way of helping the organism to heal. As the physician W J Kolff described it in 1955:
Artificial hibernation attempts to duplicate the metabolic state of the naturally hibernating animal which during winter sleep seems to be very resistant to serious injury, including temporary arrest of the circulation, and to infection … Artificial hibernation establishes, for the time, a retrograde evolution that, in emergent situations, attempts to copy the status of creatures less evolved than man himself.
The key ingredient of the ‘lytic cocktail’, a concoction invented by Laborit to induce déconnexion neurovégétative (autonomic disconnection), was initially a phenothiazine called promethazine, which was later replaced by chlorpromazine – a substance synthesised by the French company Rhône-Poulenc. Phenothiazines were originally developed for dyeing in the textile industry; they first made their way into medicine via histology (where it was necessary to dye tissue samples to visualise their microscopic structures) and then as a medicine that was thought to be effective against pathogenic agents such as the malaria parasite.
‘Artificial hibernation’ was used as an alternative to local anaesthesia for relatively mild procedures
Chlorpromazine is a remarkably promiscuous drug in the sense that it binds, and often blocks, a wide variety of receptors for endogenous neurotransmitters and neuromodulators that mediate sympathetic effects and normally act to increase levels or neural activity and arousal. The wide range of its effects inspired a variety of trade names for chlorpromazine – from Largactil (‘acting broadly’) to Hibernal. This hibernation-inducing cocktail was not expected to lead to a profound loss of consciousness, but to produce what was called, rather disturbingly, a ‘pharmacodynamic lobotomy’, a state of extreme drowsiness, sedation and reduced behavioural responsiveness.
In normal, generally healthy subjects, the effects of chlorpromazine were described as following:
[T]he subjects became drowsy, listless, calm and apathetic. Their countenances appeared very pale. Their skin generally was warm and dry but very pale rather than pink … The subjects subsequently complained of a generalised feeling of motor weakness, felt chilly and complained of thirst.
According to Kolff’s description:
[A] patient who is anxious, fighting, restless, cyanotic, and miserable, becomes calm after induction of hibernation; he does not complain about pain; he appears to be sleeping but … he will respond if you press on a broken leg or into a painful abdomen.
Artificial hibernation was found to be effective in conditions when the patient was ‘beyond recovery’, Kolff writes, such as when medics observed an uncontrollable deterioration of condition, a fall in blood pressure, convulsions or coma. However, with the growing popularity of ‘artificial hibernation’, it was used to manage other less dramatic conditions and even as an alternative to local anaesthesia for relatively mild procedures, such as bronchoscopy.
It is possible that moderate hypothermia and reduced metabolic rates induced by the ‘lytic cocktail’ were an important, if not the central, aspect of hibernotherapy. It is well known that hypothermia may help cope with a potential injury or insult, for example by dealing better with blood loss, inflammation, hypoxia or providing neuroprotection. However, the method of artificial hibernation did not survive for long. There were two possible explanations as to why this was so.
One is that it triggered some very vocal critics. In the article ‘Induced Hypothermia Is Not “Artificial Hibernation”’ (1966), the physician Alfred Henderson reminded that:
A vast number of differences exist between a cold homeotherm and a hibernating animal … [U]ntil man can apply clinical hypothermia in a manner resulting in the physiological state simulating natural hibernation, skilfully and creditably, he should refrain from deluding himself, the profession, and the laity by mislabelling his cryogenic science and skills with improper nomenclature.
The other possible reason is that the key drug used to induce artificial hibernation – chlorpromazine – became instead a paradigm-shifting neuroleptic. Neuroleptics are a class of medications used to treat psychosis, and this discovery shifted attention to other, more promising applications of the compound.
The lack of scientific theory behind the induction of artificial hibernation, and a poor understanding of the underlying biology, is likely an explanation for the lack of progress in this area. But, as scientists now take a more meticulous and careful approach, important discoveries provide new hope. In the past decades, our understanding of the molecular mechanisms, physiology and neurophysiology of sleep and hibernation have increased dramatically. Scientists have discovered brain networks and unique cell types that monitor body energy balance and are essential for thermoregulation and metabolic control. By using modern techniques, we can artificially start and end a state similar to torpor, at least in small laboratory animals, but many questions remain.
For example – what is the relationship between hibernation and sleep? Recent research in several hibernating species reveals that animals often enter the state of hibernation via sleep, as if sleep were the gateway to the state of hibernation, being the first step towards hypometabolism. Where does sleep end and hibernation begin? That’s not an easy question to answer definitively. The relationship between torpor and sleep remains poorly understood and at best confusing, not least because of a lack of clearly defined concepts in this area.
Hibernating animals appear to be sleeping, yet we define sleep using explicitly brain- and behaviour-centric criteria, such as immobility, an elevated arousal threshold and characteristic brainwaves, while hibernation and torpor are defined based on metabolic criteria. Perhaps sleep has evolved from more ‘primitive’ hypometabolic states, and the animal that goes from sleep to hibernation recapitulates that evolution in reverse? Can we perhaps even view sleep as an aborted form of hibernation, emerging when our ancestors learned to apply the break at the right moment, to remain in control of the bodily state rather than plunging into torpidity?
The pattern of brain activity during torpor indicates regression to a primordial state of brain networks
Remarkably, the profound lethargy associated with hibernation does not always mean that the organism is unresponsive and, as all researchers in the field know from first-hand experience, nothing is more disruptive to torpor than the need to interfere with the animals, for example when collecting physiological measures such as body temperature. The study in hamsters mentioned above describes how easily it can be interrupted if the animal is handled during that initial, fragile state of entrance into torpor, resulting in movement, vocalisation and a rapid rewarming. Hibernating animals need privacy, and the act of observing itself changes what is observed. Non-intrusive ways of taking measurements from a hibernating animal are often the only strategy to obtain reliable data, which can be difficult, especially in hibernating animals in the wild.
Very few studies have looked closely at the brainwaves of a hibernating animal, so this is very much an open area of investigation. Studies suggest that, at relatively high temperatures, EEG readings of a hibernating animal look similar to the patterns characteristic of sleep yet, as body temperature goes down, neural activity declines to a low, nearly iso-electric level. Such a state is often typical for brain injury or deep anaesthesia, also found in pharmacologically induced hypothermia, when brain activity is characterised by a so-called ‘burst suppression’ – an alternation of brief periods of high neural activity with silence, a flat-line EEG chart. Other examples of this type of brain activity include an immature brain in preterm babies, neonate animals or even a neuronal culture in a dish. Intriguingly, the pattern of brain activity during torpor indicates regression to a more primitive, primordial state of brain networks. It remains a biological paradox, as the body and the brain can be cold during hibernation, with metabolic rates and neural activity being just a fraction of their levels during normal wakefulness, yet someone is there who retains the capacity to monitor the environment, and responds readily if disturbed. The question naturally arises of whether being in such a dramatic state has consequences for brain function?
One striking observation made decades ago is that hibernators do not stay continuously in hibernation, but ‘dehibernate’ at regular intervals, ranging from days to weeks. This has been demonstrated first by the zoophysiologist Brian Barnes and colleagues who monitored body temperature in Arctic ground squirrels (Spermophilus parryii): upon inspecting the animals’ hibernation history over the winter, the researchers discovered periodically occurring conspicuous spikes in body temperature. For just some hours at a time, hibernating animals warm up, which entails a tremendous amount of energy, and then go back down again. Although we still don’t know why this happens, it was noticed that, during those so-called ‘euthermic arousals’, animals spend considerable time sleeping, leading to a provocative idea that they warm up from hibernation in order to sleep, and then sink back into hibernation.
Even in small torpidators, such as Djungarian hamsters, it was found that, upon rewarming from daily torpor, animals engage in deep, intense sleep, similar to the state after sleep deprivation, as if they are tired from being in a torpid state and need to catch up on some actual sleep. Why this is so remains a mystery, but one idea is that hibernation results in some sort of metabolic or synaptic imbalance that necessitates sleep for recuperation.
A number of important questions stem from this notion, such as whether and how hibernating animals retain their memories after repeated cycling into this dramatic state of metabolic depression, associated with a breakdown of synaptic networks. One study in European ground squirrels (Spermophilus citellus) showed that these animals still remember their familiar conspecifics, as measured with a social-recognition memory test after they spent many months in a state of hibernation. It appears that what is truly important is protected from forgetting. While this is certainly promising for the prospect of inducing hibernation safely in humans for long-haul space travel, scientists believe that we could also harness this remarkable state for understanding, and perhaps curing, brain disorders. Perhaps hibernation will one day be used as a means to reset abnormal modes of brain activity or bodily dyshomeostasis for therapeutic purposes.
It is tempting to compare the process of entering into and returning from hibernation with a process of dying and rebirth and, perhaps unsurprisingly, some scientists begin to evoke this metaphor when describing torpor. I already mentioned the early definition of hibernation, which was viewed as a state between life and death, and perhaps it is useful to return to this definition. Defining the boundary between being alive and dead was never an exact science, and the closeness of hibernation to death – perhaps the closest an organism can ever get while remaining alive – is among the most fascinating of its aspects. Breathing and heart rate can decrease to being near-nondetectable, the body can become cold and stiff in deep hibernation, and brain activity can be nearly absent.
Yet the state of hibernation defies death, it allows the organism to exist in another dimension, a sort of death-like deathlessness. Life is defined by the organism being there, seeing and feeling the world, changing its environment, reproducing and leaving the trace of its existence behind. Hibernation is exactly the opposite – it is a leave of absence, disappearing from the world, shrinking to nonexistence in a familiar sense, losing autonomy, relinquishing agency, not resisting the environment but blending into it. Paradoxically, this helps to escape the adversities of harsh reality – by doing nothing and by annihilating an individual’s characteristics. The less is left from a living, conscious, behaving organism, the more profound and complete, and therefore more ‘effective’, the state of hibernation is.
Animals find a way to ‘escape’ by entering a different dimension of existence – their physiology slows down
Naturally, we are envious that so many creatures, big and small, around us have mastered and perfected the skill of hibernation, which still escapes our understanding. Is it because we are too obsessed with trying to make sense of what we can see and measure, rather than noticing what is not there as its essential feature? Our efforts to understand hibernation go against its entire idea – to disappear, to disconnect, to stop time, to become one with the world. Is this why understanding hibernation eludes us?
Consider this example: when threatened, some animals enter a peculiar state called freezing, which is an extreme version of the fight-or-flight response, when it is pointless to fight and there’s nowhere to fly in the physical, 3D space. Instead, animals find a way to ‘escape’ by entering a different dimension of existence – they don’t merely stop moving, but their physiology slows down, making them less visible. Many living organisms employ a strategy of assuming a fake identity, becoming someone else, called mimicry – for example, to deceive their enemies, they pretend to be bigger or more dangerous than they are in reality.
The other form of mimicry is pretending to not be there at all, or playing dead, such as in the case of thanatosis. Could hibernation be understood as an elaborate, and rather extreme, form of mimicry – a state when the organism doesn’t simply pretend to be dead, but undergoes a profound transformation, blurring the boundary between life and death, in order to survive? Better understanding of the biological meaning of hibernation, and how it relates to other states of being and modes of existence, is necessary before we can make tangible progress in inducing artificial hibernation in humans. What if, deep down, humans always knew how to hibernate, and when conditions are right, and when it comes to the point when alternative ways to continue existing are unimaginable, we can bring back to life this forgotten ancestral memory, and enter hibernation in our own, human way?
