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One step forward for cryonics, but plenty of work remains

For years, the biostasis world has been waiting for Greg Fahy, the cryobiologist behind 21st Century Medicine’s flagship “ice-free” cryopreservation chemistry, to show something very basic: what a human brain looks like after a modern cryonics-style procedure. Because without that kind of evidence, the whole project rests on an assumption: that the brain’s information-bearing structure is preserved well enough that future technology could, in principle, recover the person.

One of the main enemies in cryopreservation is ice. Ice crystals expand as they form and can shred delicate tissue. The only place ice is truly harmless is in the emojis often used to symbolize cryonics - snowflakes, frozen faces, blocks of ice. They get the idea across instantly, even if they’re technically wrong. Cryonics, after all, is full of tradeoffs.

Among cryonics proponents, the leading strategy to avoid ice formation is vitrification: instead of freezing into ice, the tissue is loaded with a very concentrated cryoprotectant solution and cooled in a way that makes it solidify into something more like a glass than a crystal-filled block. “Glass-like” here doesn’t mean literal glass, it means a solid without ice crystals.

There’s also an older, parallel approach that has attracted attention in the brain-preservation world: aldehyde fixation. Aldehydes are chemicals that “lock” tissue in place by cross-linking proteins (like setting jelly). It’s excellent for preserving structure for microscopy, but it’s also obviously fatal by today’s medical standards, which is why vitrification without prior fixation has remained the more relevant target for “mainstream” cryonics.

This is the context in which Fahy’s new paper lands. After years of mostly indirect evidence, this was the moment when the field finally had to look at the results up close in a human case. And it could easily have gone the other way: that, once examined, showed a brain wrecked by ice, dehydration, or other microscopic damage. The kind of result that would have pushed cryonics back.

Instead, Fahy’s preprint turns out to be something more interesting: a genuine step forward. Albeit one that still leaves the hardest questions open.

Fahy is one of the central figures in modern cryobiology, associated with pushing vitrification chemistry toward something you can actually use on large, real organs, not just tiny lab samples.

The human brain in the paper belongs to Dr. L. Stephen Coles, an American biogerontologist and co-founder and executive director of the Gerontology Research Group. In 2014, Coles was dying of pancreatic cancer. He wanted to be cryopreserved. And he wanted his own case to answer the question cryonics can’t normally answer: after a real procedure, what does the brain look like up close? Coles didn’t have the money to pay, so cryonics provider Alcor covered the costs as a charity case out of its research budget - with conditions designed to make the case scientifically informative.

Those conditions included removing the brain from the skull to inspect it for cracks (vitrified tissue can become brittle at low temperatures, and brittle materials can fracture), photographing it, and taking multiple small biopsies for microscopy and other tests. Coles also wanted authorship, and Fahy’s repeated promise that this would happen has now been fulfilled.

This was, in other words, something quite unusual: a deliberately “testable” cryonics case. A planned attempt to turn a claim that’s been hard to test into something you can at least examine.

So, the paper. To recap: If you cool a brain normally, you get ice crystals, and ice is, remember, structural vandalism. To avoid ice you pump in high concentrations of cryoprotectants, and if you cool in the right way, the tissue can become glass-like rather than icy. That’s vitrification.

But those “antifreeze” cryoprotectants (like M22, developed by Fahy’s 21st Century Medicine) are so concentrated that water rushes out of tissue during perfusion. As a consequence the brain shrinks. That’s the price of avoiding ice - but it’s also the main worry, because a shrunken, dehydrated brain is harder to preserve and harder to evaluate. We’ll return to that last part in a bit.

The authors tested their approach in two steps: first in rabbits, where they could run controlled experiments on whole brains, and then in the single human case.

In rabbits, they perfused whole brains with M22, vitrified, rewarmed, and then examined the tissue under electron microscopy. They also tried partially diluting the cryoprotectant after warming to see if the shrinkage could be partly reversed without blowing up cells (removing the “antifreeze” too fast can make water flood back in and rupture the cells).

In Coles’ case, the timeline was not optimal. Before preservation even began, he had gone through roughly two days of dying-phase low blood pressure and low oxygen, and then about three hours of cold ischemia before perfusion started. That might sound like a drawback - but it’s also what makes the case valuable: in the real world you rarely get a perfect, immediate handoff, so any method that hopes to work broadly has to tolerate messy, delayed conditions. After whole-brain perfusion with M22, the team took small cortical biopsies, stored them in liquid nitrogen for years, and later processed them for imaging.

The good news: the paper shows recognizable synapses, membranes, and other cellular structures. And, importantly, they argue there’s no clear sign of catastrophic ice damage in their rabbit and human samples.

In the rabbit experiments, the tissue looked extremely squashed right after vitrification. But when the researchers carefully diluted the “antifreeze” after warming - letting some water back in - the tissue was less crushed and the fine details were easier to evaluate. Without that, you can’t really test whether the procedure preserved the brain’s information-bearing structure.

At this stage you might reasonably ask: “okay, so what?” Well, here’s the headline takeaway from the authors:

“We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.”

Yet some in the community are skeptical. Because the most important problem isn’t about spotting synapses. No, the real question is: can you preserve the brain’s fine wiring so faithfully that, in principle, you could reconstruct the person - their memories, their identity, their continuity?

Shrinking complicates that, because compressed tissue can look intact even if small breaks or lost spaces are being masked by the collapse. The paper’s best-looking “less shrunken” human results are shown mostly with light microscopy (the standard microscope), not electron microscopy (the ultra-high-resolution method needed to judge the tiniest wiring). Electron microscopy is harder to do reliably, but the paper doesn’t explain whether that’s why it wasn’t used here.

There’s another caveat too: the authors say they have a better way to remove the cryoprotectant after warming - without cells swelling and bursting as water rushes back in - but that method is referenced as unpublished work “in preparation”.

So where does that leave us?

Not with proof. And not with a debunking. But with something at the very least useful: a real data point that makes cryonics harder to dismiss as science fiction, because it moves the discussion from imagination to inspection.

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