Long-term cryosleep and reawakening may no longer be completely in the realm of science fiction thanks to the results of a new study published in the journal PNAS.
Researchers from the Friedrich-Alexander University Erlangen-Nuremberg (FAU) and the University Hospital Erlangen succeeded in freezing brain tissue from mice and then restoring its function once thawed.
While only a small portion of brain tissue was revived, the neurons were able to share electrical signals and even maintained the complex processes required for memory and learning.
“Before doing the experiment, I was not convinced this would work,” lead author Dr Alexander German, a researcher in the Molecular Neurology Department at the University Hospital Erlangen, told BBC Science Focus.
“The public takeaway should probably shift from ‘pure science fiction’ to ‘a serious long-term scientific and engineering problem.’”
Taking a leaf out of nature’s book
In some ways, nature has already figured out cryosleep. The Siberian salamander, for example, can survive at temperatures of 50°C (-58°F) below freezing, lying dormant for years in permafrost before returning to normal activity when temperatures rise.
The secret is in its liver, which produces glycerol – a natural antifreeze that prevents ice crystals from forming inside cells.
Ice formation is precisely the problem that has stymied human attempts at cryopreservation: crystals grow inside and between cells, mechanically tearing apart the delicate nanostructure of living tissue.
Yet the chemicals used to combat this bring their own problems. Many are toxic to sensitive cells and cause damaging shifts in the fluid balance inside tissue as their concentration changes.
The team’s solution was a technique called vitrification. Instead of allowing water to crystallise, vitrification replaces much of the tissue fluid with a cocktail of cryoprotective chemicals and then cools it fast enough that molecules are locked in a glass-like state. Both glass and ice are hard solids, but glass has a random structure, meaning no crystals and therefore no mechanical damage.
German and his colleagues used a custom solution called V3, carefully optimised to be as non-toxic as possible while preventing ice formation.
They then focused their experiments on the hippocampus – a small structure in the brain responsible for memory and learning.
Slices of mouse hippocampus, about three times the thickness of a human hair, were stepped through progressively higher concentrations of the V3 solution before being rapidly cooled on a liquid-nitrogen-chilled copper cylinder at −196°C (-321°F) and stored at −150°C (-238°F) for between ten minutes and seven days.
Upon thawing, the scientists found the structure of the neurons was preserved, with electrical recordings showing they were firing and communicating across the hippocampus circuitry.
But the real prize was something called long-term potentiation – LTP – a process by which frequently used connections between neurons are selectively strengthened. It is widely considered the cellular basis of how we learn and remember things, and it was still working.
That mattered to German because LTP is a punishingly demanding test of brain function. It requires a whole chain of cellular machinery to be operating at once: signalling chemicals released across synapses, specific receptors activated, calcium ions handled correctly, and a cascade of molecular events that ultimately reinforce the neuronal connection.
The fact that all of this was still operational after complete freezing suggested the tissue had survived vitrification in far better shape than expected.
“The result tells us that this synaptic machinery remained sufficiently intact to support new plasticity after complete cryogenic arrest,” German said.
Reality versus fiction
The most immediate uses are earthbound rather than interstellar. Surgeons who remove brain tissue during epilepsy operations currently have to study it straight away; a working vitrification method would let those samples be banked and revisited years later.
German's own spin-out, Hiber, is already working to turn the technique into a reliable supply of preserved human neural tissue for drug discovery and disease research.
German also pointed out that the physics of long-term storage is surprisingly encouraging. Once tissue drops below the glass transition temperature, molecular movement and chemical degradation essentially stop – there is no biological clock still ticking.
In fact, radiation may be a bigger challenge, he said, especially if such techniques are to be used in future long-distance space missions.
From tissues to organisms
Scaling from a thin tissue slice to a whole organ – let alone a whole body – remains a different problem entirely.
In a slice, cryoprotectants diffuse in from all surfaces. In an intact brain, they must be delivered and removed through blood vessels, and the blood-brain barrier makes that extremely difficult.
During rewarming, if parts were to thaw unevenly, tissues could crack or partially recrystallise, destroying the structure vitrification was meant to protect.
"Our PNAS study is a proof of principle in neural cryobiology, not a demonstration of whole-organism cryostasis," German said.
"What it shows is that adult mammalian brain tissue can recover near-physiological circuit function after complete arrest in an ice-free cryogenic glass. That is important because it removes the objection that adult brain tissue is too fragile for cryopreservation."
For German, the real significance is less cinematic than the sci-fi framing suggests. "The sober version of the sci-fi idea is not really interstellar travel; it is buying time," he says.
"If medicine can learn to preserve tissues, organs, and perhaps one day patients more effectively, then we gain a way of bridging people to better treatments in the future."
Read more:
