The miracle of hibernation
Hibernation is a mysterious phenomenon. How is it that animals are able to slow down their system for so long without suffering any damage? And wouldn’t it be great if humans could do the same?
That is exactly what Rob Henning and his team are researching. Thirty hamsters are currently hibernating in the animal testing lab at the RUG.
The animals sleep for approximately a week. During that time, they have no perceptible EEG and their body temperature is at a mere five degrees Celsius. They then warm up to 37 degrees in two and a half hours. This process would kill a human being.
Henning discovered that H2S, or hydrogen sulfide, prevents tissue damage. He synthesised a substance that ensures that the cells of non-hibernators can survive this process as well.
Now he is researching how the creatures are able to repair any DNA damaged suffered during the cold phase.
There are countless applications. Think of, for instance, the longer preservation of transplant organs. The aerospace industry is interested as well.
Reading time: 7 minutes (1542 words)
The light in the small, square space shines a muted red. It is dead silent and rather cold. At five degrees Celsius, this is not a room you want to enter just for the fun of it. And yet this is where thirty hamsters, rolled up into tiny balls in the straw, are enjoying their hibernation. To them, it’s pitch black, because hamsters don’t see red.
Soon, their slumber shall be disturbed. The motion detector that is trained on the animals has shown that one of them is about to wake up. This is the best moment to wake all of them up in order to take a buccal swab from them.
Touch is enough
PhD candidate Vera Reitsema slips into the room and takes the plastic container with the hamster that is about to wake up from the shelf. Removing the lid from the box, she carefully lifts the ball of fur from its nest. The touch and heat of her hands will ensure that within the hour, the creature will be fully warmed up and sniffing around.
‘All you have to do is touch them’, confirms head of research Rob Henning as he watches. ‘Or softly squeeze their paw. That’s enough to wake them up.’
And that, says Henning, is quite remarkable. Because if you were to take an EEG of their brain activity at the moment you pick them up, it would show nothing. You would see a flat line that might as well tell you they are dead. So how is it possible that they still register being pet, or the heat of your hands? Nobody knows.
It is just one of the many mysteries surrounding hibernation that have been fascinating Rob Henning for several years now. Hibernation is really a bizarre phenomenon, he explains.
It happens all over the animal world. There are marsupials, mice, even hummingbirds and monkeys that hibernate. ‘It’s a way of conserving energy in times of scarcity’, Henning says. ‘The animals slow down their metabolism, which lowers their body temperature and causes them to consume less energy.’
Asking for trouble
But hibernation isn’t typically the period of deep slumber that we associate with bears in their dark caves. ‘Almost all hibernators are only cold for about a week, after which they warm up from five degrees to 37 degrees Celsius in the space of an hour and half. After that, they go back into torpor, as the cold phase is also known.’
That, too, is mysterious, because cooling down and warming up over a long period of time is asking for trouble. Not even inanimate nature can handle that: it would absolutely break a rock. So how are animals able to do it with such apparent ease? Why doesn’t it cause irreparable tissue damage? How is it possible that all the cells in an organism simultaneously slow down? And – this is where Rob Henning’s background as an anaesthesiologist comes through – wouldn’t it be great if we could put human beings into hibernation as an alternative to narcosis?
And there are even more possibilities. What if you could make a kidney or liver fall ‘asleep’ and then warm it up again? That would mean that you would have much more time to find a donor, for example. Space travel would be made so much simpler – a slower metabolism means fewer supplies – and a lot less boring. Henning is part of a think tank at the European Space Agency (ESA) which ponders exactly these kinds of questions, because a journey to the salt rivers of Mars is bound to happen.
Henning is slowly but surely unravelling the mystery of hibernation. He might not yet have a clue as to what triggers every cell in the body from the earlobe to the big toe to go into torpor, but he has discovered which substance is responsible for the prevention of damage due to the cold: the gas H2S, or hydrogen sulfide.
Henning started figuring it out when a student had forgotten a hamster cell culture in the refrigerator. When the culture bottle turned up a week later, the cells should have been dead as a doornail, but they weren’t. They may have smelled terrible – like rotten eggs – but otherwise, they were completely fine.
That smell was not because they were rotten but because they were producing H2S, a gas that plays a crucial role in the prevention of tissue damage by neutralising free radicals in cells. Normally, this H2S production ceases when the body temperature falls below a certain level, but that is not the case with hibernators. Intrigued, Henning started reading up on the relevant literature and found articles that described how H2S induces a sort of hibernation in mice.
‘Could that be the reason hibernators survive the rapid warming?’ Henning wondered. It was. Hibernators produce an enzyme that then ensures that the production of H2S continues at low temperatures.
The discovery of this mechanism led to the synthesis of a series of substances. One of these substances – named Sul 121 – turned out to be a breakthrough. Henning tested it on rat cells – rats do not hibernate – and it protected them from cooling and warming up as well. ‘We patented this discovery and transferred it to a start up company’, Henning says, pleased. ‘It’s being used to longer preserve platelets, for example. It also works to preserve stem cells.’
But the implications for this technique are great. For instance, there are metabolic disorders where people don’t produce enough H2S. Children afflicted by this disease often die young. But in aging-associated diseases such as diabetes, Parkinson’s, or Alzheimer’s disease, problems with the production of hydrogen sulfide also play a role.
In the meantime, Henning has moved on to the next question. Although H2S protects the hamsters from cell damage due to the rapid warming, that does not mean they all come out of hibernation unscathed. ‘Directly after they wake up, there appears to be damage done to the DNA.’
Henning researches the damage to the DNA and collects data for colleagues who research damage to telomeres – the pieces of DNA at the end of a chromosome that become shorter as a person ages. Funnily enough, an hour and a half after the hamsters have woken up, there is no trace of the damage to be found. But if and how hibernators prevent permanent damage remains unknown.
It’s not just Henning who wants to know this; the ESA is also very interested. Think about it: Obama has plans for a journey to Mars in approximately twenty years, and Europe and China want to go there as well. But a manned flight won’t be possible until a solution is found for the damage astronauts suffer from cosmic radiation when undertaking such a long journey.
House of cards
And so the thirty sleeping hamsters in the animal testing lab have been injected with a tracer, which shows precisely were the DNA is damaged. PhD candidates take samples before the creatures go into torpor, directly after they’ve woken up and once they’ve completely warmed up.
‘It’s fascinating’, says Henning. Of course, our DNA gets damaged a little every day and most of the time we are able to handle that just fine. But it appears as though hibernators suffer much more DNA damage during a cold phase. ‘Many people think that’s why hibernators warm up: to repair the damage before the whole system collapses like a house of cards.’
The research is fully under way. Approximately thirty hamsters have already been examined and the data this has provided is being studied. The other thirty hamsters will sleep on for a little while longer.