The biggest objection I get to end-of-life preservation goes like this: “We can’t revive today, so we can’t prove that preservation works. Therefore preservation probably doesn’t work. We shouldn’t bother with preservation until we can revive.” I call this the immediate revival objection.

I respect the immediate revival objection. If your standard of evidence is full recovery, then you don’t need any knowledge of how people or mental processes work on the inside to evaluate preservation; you can just observe that they survive a round trip.

I think requiring revival, now, is reasonable a priori—it’s analogous to how I feel when people talk about new kinds of quantum computers: I’ll believe it when they’re actually doing something useful.

However, in my opinion the logic of the immediate revival objection is too conservative when it comes to end-of-life preservation. Instead, I think that as a scientific community, we’ve known enough to preserve people for at least 30 years. I think we can and should start preserving people today. I think if you knew what I know, you’d agree.

Why do I think that? What’s my response to the immediate revival objection? How do I know what I think I know?

The San Diego Frozen Zoo

Dr. Kurt Benirschke started the San Diego Frozen Zoo in 1975. It just celebrated its 50th anniversary. Benirschke had the visionary idea to preserve cells from endangered animal species using liquid nitrogen, with the belief that people in the future would probably want them. DNA had been shown to be a durable, double-helix-shaped polymer in 1953, and successful cryopreservation of sperm had been achieved in 1949, so Dr. Benirschke was in a position to understand that animal cells each separately held the “molecule of heredity” and were preservable by cold.

That’s all he needed to begin preserving. And today, after 50 years in storage, samples are now starting to be used.

Think of the state of our biological knowledge when the San Diego Frozen Zoo opened: no one understood what DNA meant at a programmatic level, no one had cloned a mammal, and Kary Mullis wouldn’t go on his fateful LSD trip and invent PCR for another decade. The idea of using preserved DNA to revive an extinct species, in 1975, probably sounded just as far-fetched as scanning and simulating a preserved brain does today.2

Dr. Benirschke preserved cells anyway. He didn’t need to know exactly how they would be used. He did his job well and gave us, today, an option we wouldn’t otherwise have.

What can we learn from the example of the San Diego Frozen Zoo? There’s two lessons I take from it:

1. Only basic knowledge is needed to preserve. You might think that you need to have masterful knowledge of the thing you’re preserving in order to preserve it. But Dr. Benirschke didn’t have masterful knowledge of DNA, he only had basic knowledge, and that was clearly enough. The amount of knowledge needed to preserve something is often vastly less than that needed to actually do anything with that you’re preserving.

2. Preservation can work before you can revive. You might think that if you don’t know everything about what you’re preserving, then you need to at least be able to “unpreserve” to have anything worthwhile. But the San Diego Frozen Zoo preserved animal cells before the invention of PCR, before the first successful cloning of a mammal, before they had conclusive proof that what they were preserving would be useful. I’m sure they faced criticism along the lines of “how could a few cells ever be useful for species conservation?”, “how could we ever fit a whole genome on a computer?”, “why are you wasting money on something that might never be used?”. These questions turned out to be focused on the wrong thing. What mattered was whether preservation captured the necessary information. The founders of the Frozen Zoo didn’t know exactly how their cells would be used, and they didn’t need to in order for their project of preservation to be useful. In the words of Dr. Kurt Benirschke, “you must collect things for reasons you don’t yet understand.”

3. The time to start preserving is when you’re reasonably confident you can do the preservation, not after you’ve demonstrated how to use what you’re preserving.3 The San Diego Frozen Zoo successfully preserved animal cells in the early 70s, before anyone knew very much about what DNA meant or how proteins folded or how to manipulate DNA. They didn’t know how or if the cells they were preserving would ever be used. But despite their ignorance, the chemical and biological knowledge of the 1970s was up to the modest task of showing that preserving even a few animal cells almost certainly preserved many copies of the animal’s genome, and that a few preserved cells would likely be sufficient to “remember” what a species was, and that was clearly the right time to start.4

I believe that today when it comes to preserving people we’re in an analogous position with neuroscience as we were with genetics in the 1970s: We have more than sufficient knowledge to confidently preserve, but not enough to do much with what we’re preserving. Yet.

Preserving People

Why do I think the lessons of the San Diego Frozen Zoo apply to human end-of-life preservation?

I’ll start with a neuroscience overview. What’s your brain physically made of? How does it store information? I’ll only cover the basics, the stuff that was already well-established more than 20 years ago, because we don’t need more than the basics. Like Dr. Benirschke of the San Diego Frozen Zoo, we don’t need a complete understanding of neuroscience to know enough to preserve.

Then I’ll talk about how fixation physically works and what it can and can’t preserve.

Next I’ll briefly touch on Deep Hypothermic Circulatory Arrest, which I’ve written about before. DHCA demonstrates that we don’t have to preserve dynamic brain activity, only structure, because people recover from having that activity “zeroed out”.

Finally I’ll put it all together in information-theoretic terms and develop a formal definition of adequacy for a preservation technique. Fixation’s good at preserving structure, but is it good enough? We’ll use the framework to evaluate whether fixation can preserve what we really care about: people.

What does neuroscience say about how the brain encodes information structurally?

Top level summary: it turns out that to create a long-term behavioral change, neuroscience says you must physically change multiple synapses. Synapses, broadly, are the durable physical trace of memory we’re looking to preserve.

Important: I don’t need neuroscience to be “complete” to evaluate whether preservation works. I need to understand the basics of what the brain’s made of and what’s physically different between different people. These are basic facts we need to know, and we’ve had the basics for a while—none of it has changed for decades. This section is here, not to review advanced neuroscience, but to celebrate that we really do know the basics of the brain enough to justify preservation.

Conversations with neuroscientists

If you walk up to a neuroscientist and say: “hey we know a lot about neuroscience, so how soon before we upload the first person like I saw in ‘Pantheon‘?”, that neuroscientist will probably say something along the lines of “We know nothing about the brain. We’re so far from uploading that it won’t happen for 100 years. There are major open questions in neuroscience about how the brain works, individual cells have vast complexity, and we can’t even simulate a C. elegans yet. No one knows how memory works—we’re still working on decoding even the simplest memories and there are all kinds of theories.”

Now imagine you walk up to that same neuroscientist and say: “No one knows anything about the brain! Despite the efforts of science it remains a complete mystery! For all we know, a rock could be conscious. Maybe even the whole universe is conscious! Isn’t that neat?” That neuroscientist would probably say something like: “What do you mean ‘we don’t know anything about the brain’? We know a lot about the brain! Neuroscientists have done 75 years of amazing work since Hodgkin and Huxley figured out how the ionic dynamics of the action potential worked. We can erase memories by altering synapses. We can create false memories in mice using optogenetics. We’ve spent decades working out how the biochemistry of synapses works and we have what amounts to a ‘parts list’ at a proteomic level. We’ve mapped the fruit fly connectome and accurately simulated its visual system. We actually know quite a bit about how the brain works, how memories are formed, how it processes information. There are a lot of mysteries, sure. We don’t know how a lot of stuff works at a systems level. But we know a lot about the basics. A rock is not conscious.”

What’s inside your head?

Let’s talk about what scientists do know about the brain, starting with its basic anatomy. When you open up a skull and look inside, what do you see?

The large-scale: white matter and grey matter

First off, your brain has two obviously different parts to it: 500 ml of white matter and 650 ml of grey matter. There’s also around 200 ml of apparently empty space (ventricles) filled with clear fluid (cerebral spinal fluid, or CSF) (Irimia 2021).

The white matter, visually, looks like a vast bundle of wires connecting the grey matter to other parts of itself. The grey matter is where the neuron cell bodies live. You may think, as I used to, that neurons are very small. This is not the case! A single projection neuron in the right hemisphere might grow an axon that extends across the corpus callosum and connects with another neuron in the grey matter of the left hemisphere. That’s a single cell that’s 10 cm long! The bundles of fibers in the white matter are all literally extensions of the neurons in the grey matter.

There’s some blood in your brain in addition to the white and grey matter, but probably not as much as you think. All the blood vessels in the brain amount to about 50 ml in total.5 Around half is capillaries, each itself as wide as a single red blood cell, and the other half is larger blood vessels. Only capillaries are thin enough to allow the interchange of oxygen and sugar between blood and brain which nourishes each of your neurons.6 Capillaries penetrate every part of the brain, and a brain cell is never very far from one. Capillaries are much denser in the grey matter (~5.5% of volume) where the cell bodies are, and sparser in the white matter (~1.5% of volume) (Lu 2005, Gould 2016).

What does the brain look like at a microscopic level?

The vast majority of the grey matter, around 75%, is “neuropil”, with less than 15-25% being cell bodies and blood vessels (Cano-Astorga 2024) .

That’s a lot of volume dedicated to “neuropil”! What’s neuropil made of? It’s almost entirely synapses, axons, dendrites, and glial cells. Synapses, axons, and dendrites are all different parts of the anatomy of the neurons, whose cell bodies live in the grey matter. Axons are, broadly, the “output” part of the neuron, and dendrites are the “input” part. Synapses are what join the outputs to the inputs.

Within the neuropil itself, axons and dendrites each take up ~33% each of the total volume (Karbowski 2015). Glial processes take up ~14% of the volume. Synapses take up the remaining ~20% (Wilhelm 2014).7

White matter has far fewer cell bodies and blood vessels compared to grey matter, being almost entirely composed of long-range “wires” (axons) connecting neurons in different regions of grey matter across centimeters. (Coelho 2018). It’s essentially neuropil that’s all “output”.

What about energy use?

Energy is not used frivolously in biology. If something is using energy, it’s because it’s doing something important. Doubly so if it’s using a disproportionate amount of energy.

How does a person spend their internal energy? First off, the brain is hungry! Your brain consumes 20% of your body’s energy, but it’s only around 2% of your body’s mass (Mink 1981). The brain is important energetically.

How does the brain spend its energy? At a high level, the white matter takes about 25% and the grey matter takes the other 75%, despite them being approximately the same volume (Harris 2012). The grey matter is important energetically.

How does the grey matter spend its energy? First, around 25% of the total energy is used to continuously rebuild the proteins and other macromolecules of each cell (housekeeping). About 15% of the energy is used to create action potentials, and an additional 15% is used to maintain baseline polarization of neurons at around -70 mV (keeping the lights on). The rest of the energy (45%) is used to power synapses (Howarth 2012), despite them being 20% of the grey matter’s volume. Like the brain itself, synapses consume disproportionately large amounts of energy.

Synapses seem important!

Synapses are each around half a femtoliter in volume (Wilhelm 2014, Benavides-Piccione 2012) and you have around 250 trillion in total (Tang 2001).8

What do those hundreds of trillions of synapses, using so much of the brain’s energy, do?

Synapses change when memories change

Synapses change shape when memories are formed (Choi 2021). The physical changes synapses undergo in response to learning aren’t subtle, often doubling or halving their size (Matsuzaki 2004). You can label which synapses change during memory formation, and if you “reset” just those synapses, you erase that specific memory, and not other memories learned both shortly before and after the memory you delete (Hayashi-Takagi 2015). When you disrupt synaptic plasticity machinery, you can temporarily prevent long-term memory formation (Goto 2021). You can create false memories by artificially strengthening new synapses (Vetere 2019). Synapses operate at millisecond timescales and nerve impulses travel quickly throughout the brain and body, which are exactly the right dynamics for the speed of our thoughts. Synapses can last a lifetime (Bhatt 2009, Yang 2009).

Here’s what synapses look like at a molecular level

I didn’t appreciate this when I first started preserving brains, but a synapse (as well as every cell in the body) is absolutely full of proteins, as you can see in the picture above (which again is only showing around 1/3rd of the proteins!). Before I saw models like this, I thought that cells were mostly empty bags of water with proteins elegantly doing their thing, gliding past each other with plenty of “elbow room” between proteins, as is often depicted in many visualizations. I now find myself surprised that cells are even liquid at all, instead of solid peptide blocks.9

Synapses changes size by fractions of a femtoliter in response to memory formation, which changes their “strength” (how much they influence the neuron to which they connect, electrophysiologically). What changes when a synapse changes size by a fraction of a femtoliter? A volume like that is small at our scale, but huge at an atomic scale. If a synapse expands by half a femtoliter, it’s adding roughly 500,000 additional proteins, each containing around 10,000 individual atoms (Wilhelm 2014).10

Synapses are durable

We saw in my previous post that the surgical procedure called deep hypothermic circulatory arrest (DHCA) cools people to 16°C, stops respiration and circulation, effectively zeros out the dynamic electrical state of the nervous system, yet doesn’t erase long-term memory. We need some durable physical substrate of memory that survives cooling to explain this. Do synapses physically survive the cooling used during DHCA, unlike the brain’s electrical activity? Yes! (Xie 2012)

Synapses are the physical basis of learning and memory

When we look inside the brain we see, essentially, two-hundred-and-fifty trillion femtoliter-sized switches which grow and shrink by fractions of a femtoliter in response to learning.

The actual cell bodies in the grey matter don’t change in response to learning. Neither do the long-range connections in the white matter, or the blood vessels spread throughout the brain. But in the neuropil, we see that it’s synapses that change in response to learning, while being physically robust enough to survive DHCA.11 That’s why I believe that synapses are the physical trace of memory. What does the broader neuroscience literature say?

What do neuroscience review papers and textbooks say?

The field of neuroscience is broadly in consensus, and has been for many decades at this point: synapses are the physical basis of learning and memory.

I think it’s worth understanding just how established this picture of the mind and brain is. So here are twenty distinct sources from noteworthy neuroscience papers and textbooks that all point to the same bottom line. (Emphasis added):

“Perhaps the most striking finding in the cell biology of memory is that the consolidation and long-term storage of memory involves transcription in the nucleus and structural changes at the synapse. These structural components of learning-related synaptic plasticity can be grouped into two general categories: (1) remodeling and enlargement of preexisting synapses, and (2) alterations in the number of synapses, including both the addition and elimination of synaptic connections.”
Bailey, Kandel, and Harris 2015

“The classic view is that items are embedded in long term memory via specific synaptic modifications, and presentation of these items leads to activation of stable activity patterns in the network (‘attractors’).”
Barak and Tsodyks 2014

“Learning is primarily mediated by activity-dependent modifications of synaptic strength within neuronal circuits.”
Bittner et al. 2017

“[The] ability of synapses to individually change their structure and composition in a long-lasting way is an essential mechanism for synaptic plasticity and represents the cellular basis of learning and memory.”
Bosch et al. 2014

“Today, it is generally accepted that the neurobiological substrate of memories resides in activity driven modifications of synaptic strength and structural remodeling of neural networks activated during learning.”
Bruel-Jungerman et al. 2007

“Long-lasting changes in the synaptic connectivity between neurons are generally accepted to be crucial for the establishment and maintenance of memories.”
Gobbo et al. 2017

“It is generally believed that changes in the synaptic connections between neurons play a major role in learning and memory formation. While short-term memory might rely mainly on the strengthening and weakening of pre-existing synapses, long-term storage of information is thought to require structural reorganization of neuronal networks, the formation of new synapses and the loss of existing connections.”
Hofer and Bonhoeffer 2010

“One of the chief ideas we shall develop in this book is that the specificity of the synaptic connections established during development underlie perception, action, emotion, and learning.”
Kandel et al. Principles of Neural Science 2021

“Synaptic plasticity is generally accepted as the principal implementation of information storage in neural systems.”
Kukushkin and Carew 2017

“In the quest for the physical substrate of learning and memory, a consensus gradually emerges that memory traces are stored in specific neuronal populations and the synaptic circuits that connect them.”
Lu & Zuo 2021

“From a neural circuit point of view, learning is a process to transform a neural network to adapt to the environment, and memory is the state of maintaining such a network… Various forms of synaptic plasticity, the persistent change in synaptic efficacy, are widely believed to be the cellular substrate underlying learning and memory. Among them, long-term potentiation (LTP) and long-term depression (LTD), two opposite forms of synaptic plasticity, have been studied most extensively. LTP and LTD were initially discovered by electrophysiological recording, but subsequent research has revealed accompanying morphological changes in dendritic spines.”
Ma & Zuo 2021

“It is widely believed that encoding and storing memories in the brain requires changes in the number, structure, or function of synapses… This axiomatic view that synaptic plasticity is critical for learning and memory is supported by data derived from many different memory systems, neural circuits, and molecular pathways mediating an array of different behaviors.”
Maren 2005

“Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system… We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory…”
Martin, Grimwood, and Morris 2000

“We now understand in considerable molecular detail the mechanisms underlying long-term synaptic plasticity and the importance that such plastic changes play in memory storage, across a broad range of species and forms of memory. One surprising finding is the remarkable degree of conservation of memory mechanisms in different brain regions within a species and across species widely separated by evolution.”
Mayford, Siegelbaum, and Kandel 2012

“Memories are believed to be stored as long-lasting structural changes in synapses.”
Moczulska et al. 2013

“[I]n the last 10 years findings from this field have provided key contributions towards establishing the idea that stable, long-lasting changes in synaptic function underlie learning and memory.”
Silva 2003

“Considerable evidence suggests that the formation of long-term memories requires a critical period of new protein synthesis… Studies in mammals have demonstrated that bidirectional changes in synaptic growth accompany synaptic plasticity.
Sutton & Schuman 2006

“At the molecular level, the formation and consolidation of long-term memory are thought to be ultimately expressed in the form of structural changes at synapses.”
Wittenberg, Sullivan & Tsien 2002

“Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.”
Xu et al. 2009

“The obvious site to compactly store information is at the synapse. Storage occurs by changing its transfer ‘weight,’ that is, its ability to excite or inhibit a postsynaptic neuron. Since the synapse is the key site for processing information, storing it there avoids additional wire for relay. Moreover, information stored directly at a synapse can be retrieved directly—also avoiding additional wire. In short, as we peruse a blueprint of brain design, we should not seek a special organ for ‘information storage’—it is stored, as it should be, in every circuit.” (Chapter 14)
Sterling and Laughlin 2017 Principles of Neural Design

What does chemical fixation do?

Our protocol for preserving people at Nectome calls for chemical fixation of every cell via vascular perfusion of aldehydes. We use an aldehyde called glutaraldehyde to achieve fixation. It’s fixation that’s our primary and most important method for achieving preservation.

I believe that fixation, as used in Nectome’s method, preserves the microscopic and large-scale anatomy of a person’s brain and body, including, importantly, all synapses. I believe that in addition to structure, fixation additionally preserves almost all biological macromolecules present in a person’s entire body including proteins, nucleic acids like DNA and RNA, and lipids, in almost the same configuration they had during life.

Why do I believe this?

What does glutaraldehyde actually do?

Glutaraldehyde is a kind of aldehyde (formaldehyde is also an aldehyde) used to preserve tissue. You couldn’t see a single molecule of glutaraldehyde if you tried to accurately draw it in any of the previous images in this post, because it would take up less than 1% of a pixel even in the earlier image showing synaptic proteins. Glutaraldehyde has a molecular weight of 100.12 g/mol, while the individual proteins pictured are around 30,000 g/mol. During preservation, we flood the vascular system with glutaraldehyde. It crosses cell membranes in seconds (Leung 2001, Walter 1986) and starts crosslinking proteins to themselves and to other proteins. After around 60 seconds, the cytoplasm forms a gel that traps essentially all proteins, DNA, lipids, etc in-place (Huebinger 2018).

Why do I believe that proteins are preserved?

Immunohistochemistry

Why do I think that proteins are still present after fixation? Mainly because we can still observe proteins after fixation: the field of immunohistochemistry is built on measuring the positions and amounts of proteins in cells using antibody staining. One of the first steps of preparation of tissue for immunohistochemistry is to fix proteins with aldehydes. Check out the Supplemental Figures from (Wilhelm 2014), the same paper the protein-level synapse model from the last section is from. Those researchers studied the vesicle transport proteins that make up about 1/3rd of the total proteins by weight in a synapse. That’s ~300,000 total proteins split into 62 different kinds of proteins. (A synapse has around 1,000-2,000 different kinds of proteins and ~1,000,000 total proteins in half a femtoliter.) For each of those 62 proteins, they used antibodies after fixation to find where they are inside the synapse. That shows that the proteins are still there and that they’re still identifiable with antibody labeling. Not a single one of the proteins they examined was removed by the fixation process, and those proteins were selected based on being part of vesicle transport, not being able to be preserved by glutaraldehyde, so it’s likely most other proteins are likewise preserved.

Bulk protein measurements

What if, in a hypothetical world, fixation just removed half of all the proteins but kept the other half? Then immunohistochemistry might find that “all the different kinds of proteins are present” even though a substantial number are lost in an absolute sense. How can we distinguish between “extractive fixation” and “comprehensive fixation”?

I believe that most of the “stuff” present before preservation is still there after fixation, because bulk protein measurements can’t measure a difference in protein content between fixed vs frozen tissue. In (Ostasiewicz 2010), the researchers took rats and measured the protein content of fresh-frozen brain tissue vs the protein content of brain tissue that they fixed and then paraffin embedded, which includes total removal of all water and many lipids via alcohol and xylene dehydration and infiltration of paraffin wax into the tissue. Here’s their results:

Protein content after fixation is my second-favorite null result in science.12 We’ll get to my favorite later.

Other biological macromolecules like lipids (Morgan 1967, Leist 1986) and DNA (Tokuda 1990)13 are also retained during fixation.

Why do I believe microscopic anatomy is preserved?

It’s useful to know that biomolecules are likely preserved by fixation, but it’s possible that biomolecules would be retained while the microscopic anatomy is scrambled. How do we know, for example, whether synapses are created, destroyed, or moved during fixation, even while the underlying biomolecules are preserved? Suppose that during the 60 seconds of fixation before the cytoplasm gels and further microscopic movement becomes impossible, that a neuron writhes and randomly disconnects and reconnects its synapses? That might would result in some potentially normal-looking microanatomy and all proteins retained, but in reality the preserved microstructure would not accurately reflect the living microstructure. How do we know, when we look at seemingly well-preserved tissue, that the connections we see are the same connections that were present before preservation?

I believe that fixation preserves the brain’s microanatomy because of the correlative microscopy studies that have been done where researchers used superresolution two-photon microscopy to take a picture of a section of a single neuron and its synapses, preserved the entire brain with fixatives, and then found that exact neuron again and imaged it with electron microscopy.

This isn’t a one-off image, it’s an example taken from a paper from the large and growing field of Correlated Light and Electron Microscopy (CLEM). This particular paper impressed the Brain Preservation Foundation enough to be nominated for its Aspirational Neuroscience Prize.

I’d be surprised if fixation altered the brain’s synaptic connections—I don’t know any compelling first-principles reason for fixation to disrupt synapses during crosslinking (on the contrary, it should stabilize them), and when people directly measure physical changes from fixation, they find the same synapses before and after. Fixation directly altering synapses in a way that still looks anatomically normal afterward would, however, be the kind of thing that could invalidate Nectome’s preservation protocol, even in spite of us winning the brain preservation prize, so I take it seriously.

Deep Hypothermic Circulatory Arrest teaches us that we don’t need to preserve dynamic activity

So far we’ve talked about the physical structure of the brain and fixation’s ability to preserve that structure. But what about the dynamics—the second-to-second changes in ion concentration, neurotransmitters, voltages, etc?

I don’t believe dynamic activity is necessary to preserve. I realize this is an extremely convenient belief for someone who runs a preservation company that’s really good at preserving structure and unable to preserve dynamics. But the causality actually goes the other way: when I first learned that dynamic brain activity can be zeroed out without loss of information, in Sebastian Seung’s intro to neuroscience class at MIT, that’s what actually got me interested in preservation in the first place.

Why do I think the brain’s dynamics can be zeroed out without loss of information? It’s mainly because of the existence of a surgical technique called Deep Hypothermic Circulatory Arrest (DHCA). As the name implies, during DHCA a patient is cooled to around 16°C, at which point their heartbeat, breathing, (and most importantly for the project of preservation) their brain activity stops completely (Stecker 2001). Why would a surgeon want to cool someone to 16°C? Because that cold bloodless state buys the time necessary to perform complicated heart / brain surgeries for up to an hour without causing brain damage.

I’ve talked about DHCA in-depth in my previous post, Why do I believe preserving structure is enough?. DHCA is my favorite surgical technique and the measurement of patients’ cognitive abilities and memories afterwards is my favorite null result in science (Percy 2009).

Biological attractors mean information is stored redundantly

What if there’s a protein of some kind that’s uniquely critical for memory, has low copy number, and is lost during fixation but not during DHCA? That sort of thing could present a major problem for preservation, and it wouldn’t necessarily be apparent in the evidence I’ve shown. Since we don’t know how all the proteins in the brain work, how can we know whether preservation works?

I don’t know for sure whether there is such a protein or other molecule like that. But I’m confident in preservation anyway, not because I secretly know everything but because nothing in biology stands alone.

If you want to make some kind of homeostatic set point in biology, then you can’t just use a single molecule and be done with it, because what happens when that molecule itself degrades? Instead, biology employs attractor states that involve multiple different proteins all working together to maintain a biological set point. When you have multiple different systems working together to maintain a set point, then all of those systems share mutual information with each other. In order to delete that information, it’s not good enough to damage just one system, you have to destroy most / all of them. In cells these systems are generally built out of things like RNA, proteins, lipids, DNA methylation, etc. And all of these things are preserved by fixation.

Take AMPA receptor trafficking, for example.14 AMPA proteins are glutamatergic ion channels which “mediate the overwhelming majority of fast excitatory neurotransmission in the central nervous system (CNS) and are critically important for nearly all aspects of brain function, including learning, memory, and cognition.” (Henley 2013). Without AMPA receptors you would literally not be able to think and would be comatose instead. They’re working right now as you read the words on this page.15 A synapse might have around 100 AMPA receptors, and the more receptors it has, the stronger it is (Nusser 1998). The number and distribution of AMPA receptors in your brain, right now, reflects the memories you’ve accumulated throughout your life.

And yet, an individual AMPA receptor’s half-life is only 30 hours (Archibald 1998)—the very ion channels you’re using to think with right now are probably completely different molecules than the ones you had last week!16

What does persist is the pattern. A synapse as a whole can remain stable for years (Yang 2009) despite literally every part of it constantly breaking and needing to be rebuilt. How does a synapse do it? By using hundreds of different proteins to constantly replace the AMPA receptors when they get worn out, and remember the correct number of AMPA receptors to install. Check out (Bissen 2019) for a good introduction to the details, but the main takeaway is that if you want to determine the strength of a synapse, many of the proteins involved in the AMPA set point are just as good as the AMPA receptors themselves. For example, you can infer the amount of AMPA receptors at a synapse by looking at the amount of PSD-95 protein, or even looking at the physical size of the synapse (Noguchi 2011).

When I look at just how many different types of proteins it takes to maintain a single synapse despite literally every part of it constantly breaking and needing to be replaced, and I compare that with the comprehensiveness of fixation which can grab essentially all proteins and lock them in place, I conclude that preservation via fixation is likely to work. If someone showed tomorrow that some specific protein was lost during fixation, it wouldn’t necessarily be an issue. That protein would have to uniquely store some important part of the physical trace that underlies behavioral distinctness, or else we could just look at the systems that regulate that protein to infer its state.

Information theory ties it all together

So far I’ve shown three things:

1. It’s the current consensus of the neuroscience community that the brain physically stores information using synapses, femtoliter-sized structures that physically change in response to memory formation.

2. Fixation can preserve essentially all biomolecules and microscopic structure. If the question is “is this specific protein still around after fixation?”, the answer is very likely yes, for any protein. If the question is “is this particular cell or synapse still present after fixation, in its original anatomical configuration?”, the answer’s yes, for every cell and synapse in the entire body.

3. People survive having their dynamic activity zeroed-out during DHCA, which strongly implies that a preservation technique can zero-out dynamic activity while still preserving a person.

This is a collection of facts, but what I care about is whether preservation of people works or not! Can we do better than simply waiting for a revival to happen? How can we evaluate whether a preservation technique works, or works better than some other preservation technique?

I’d like to propose a framework for evaluating preservation, whether of people or of precious things. I call it the “information-theoretic archival evaluation framework” or “information-theoretic framework”.

In information theory, a transformation that preserves information17 is called an injective mapping, where data is moved to a different format or system, but all the information is still there. Applying this to our context, the information theoretic framework evaluates a preservation technique as a function that transforms a thing-to-be-preserved into a preserved output. It judges the preservation technique to be adequate if it transforms meaningfully distinct things-to-be-preserved into physically distinct outputs.18

I think the information-theoretic framework for evaluating preservation is the right standard to use today. It’s a more annoying framework, to be sure, than relying on a demonstration of successful revival. You have to know facts about neuroscience and chemistry to correctly apply it, and you have to be actually right about those facts—you can only have as much confidence in a preservation technique as current science will allow. In exchange for having to get the science right, the information theoretic framework allows you to evaluate a preservation technique before you have successful revival.

Behavioral distinctness is a sufficient measure of difference when it comes to preserving people

With the information theoretic evaluation framework, we judge a preservation technique to be adequate if it transforms meaningfully distinct things-to-be-preserved into physically distinct outputs. In order to apply the information theoretic evaluation framework to end-of-life preservation, we need to know two things:

1. What does it mean for one person to be “meaningfully distinct” from another?

2. Does end-of-life preservation preserve that distinctness?

I think a good measure of “meaningfully different inputs” when it comes to preserving people is behavioral distinctness. Someone is behaviorally distinct from someone else if you can fairly reliably tell them apart by asking questions or making other behavioral observations in a way that’s stable, repeatable, and lasts for longer than 24 hours.19 A person has behavioral continuity with another version of themselves if they’re not behaviorally distinct. Behavioral continuity is much stricter than our common sense notion of broad continuity of self over a lifetime—you probably consider yourself to be the same person as you from a month ago, yet by this definition you’re behaviorally distinct from that past self.

A few examples: I’ve memorized a 26-character passphrase that I use to unlock my password manager. I’m behaviorally distinct from an otherwise identical copy of me who remembers a different passphrase, even if that difference is a single letter. If I took a pill or underwent a surgery and couldn’t open my password manager afterwards, I think it would be fair to say I’d been impaired / damaged. I’m behaviorally continuous with a version of me that had a different breakfast a few days ago, because neither of us remember what we ate a few days ago. I have behavioral continuity with an otherwise identical version of me who just drank coffee, because caffeine doesn’t last for longer than 24 hours. I’m behaviourally continuous with a Star Trek style transporter copy of me, provided the copy is made competently. Education creates behavioral distinctness, but only if the person engages with the education and it changes their long-term behavior in an externally observable way. Anesthesia preserves behavioral continuity. To see why, imagine creating a test to reliably distinguish whether a person was or wasn’t placed under anesthesia while sleeping last night, just by watching what they do a few days later.

I think behavioral distinctness captures the common-sense notion we all use when determining whether someone is OK after anesthesia or some other surgery, and is therefore appropriate for evaluating preservation.20

Conclusion: let’s preserve today, with confidence

In summary:

• We can evaluate whether preservation works before we can revive. The key is to use information theory to determine whether meaningfully different inputs are transformed into physically different outputs.

• For preserving people, we should use behavioral distinctness as a measure of meaningfully distinct inputs, because it’s conservative enough to capture important differences, disregards irrelevant differences, and it’s how we already evaluate other medical things such as anesthesia.

• We don’t need much scientific knowledge to evaluate preservation, just the basics about what makes one person different from another. Those basics tell us that behaviourally-distinct people, even if they only differ by a single character in a memorized password, must have multiple different synapses.

• Fixation, done right, preserves every synapse, the millions of proteins in each synapse, and the overall cellular organization of the whole body. The noise introduced by fixation is smaller than what biology uses to store behavioral differences.

• Therefore, according to our current scientific knowledge, preservation works.

• We may be wrong. That’s the cost of preserving before you can revive. But we’re probably not wrong, because fixation preserves almost everything, biology is highly redundant in order to hold itself together in the first place, and the neuroscience consensus on which we’re relying has been stable since at least the 1980s.

• Preservation is not revival. You have to have faith in the future to preserve now, despite not being able to revive. But this kind of faith is historically correct. Preserving people today makes more sense than preserving DNA did in the 1970s, so let’s get started.

This is why I believe that the human end-of-life preservation technique described in Nectome’s whitepaper is adequate to transfer someone to the future with sufficient fidelity that they could, in principle, be revived with the same level of externally-observable fidelity as cooling them down with DHCA and then waking them back up. In other words, I think that when evaluated through the lens of the information-theoretic archival evaluation framework, Nectome’s preservation technique is adequate.

Up till now I’ve been talking about Nectome’s recent advances in structural preservation, and what that means for the immediate concerns of doing preservation to our standards. With this post I want to do something different: I want to talk about Nectome’s future and how we’re thinking about long-term care of people who entrust their preservation to us.

In contrast to the last posts where I had experiments and images to back up what I was saying, this post is more speculative. I’ve spent the last ten years thinking about how to do long-term care for people: I’ve talked with lawyers and hedge fund managers; I’ve studied the world’s end of life laws; I’ve listened to people like Mike Darwin tell the stories of past cryonics attempts. We have a lot of great business advisors among our investors who care about us succeeding. But I’m not an expert at long-term organizational stability the way I am for preservation. And making a good long-term plan is intrinsically harder than doing preservations well, in my opinion, because it’s far less constrained to deal with the uncertain future than it is to do a surgery well.

I want to talk about our current default plan for long-term care, and our reasons behind it, and then I want you to give me your thoughts. I think I have a lot to learn from people who’ve also spent a lot of time thinking about the future. I hope that Nectome will ultimately be a lot stronger because we got good feedback early on from the kinds of people who read these posts.

Robust to outages and cheap to maintain

The first and most immediate concern for long-term safekeeping of our clients is their physical long-term integrity. What happens if the power goes out? What about a natural disaster? What if we need to move them quickly? Basically, how will we keep people physically safe?

Traditional cryonics uses -196°C, the temperature of boiling liquid nitrogen. While it provides long-term stability, it’s expensive and vulnerable to supply disruption. In idealized pure-cold cryo, the goal is to chill the body until it forms a solid glass; to sustain this glassy state, you need a constant supply of liquid nitrogen, and a team of people to replenish the supply. If and when that supply chain ever breaks, people preserved this way begin to thaw within a month.

This is even worse than it sounds, because there’s an intermediate danger zone between “glassy”(around -130°C) and “liquid” (around -40°C): passing through it causes catastrophic damage as ice forms in the brain during a process called devitrification. A cryonics patient who warms to room temperature passes through this zone twice before returning to their proper temperature – once on the way up, once on the way down again. This must be avoided at all costs, meaning that traditional cryonics has to have 100% uptime; cryonics patients actually can’t be warmed up without sophisticated technology like microwave-based rewarming that hasn’t been perfected yet.

In contrast, the aldehyde-based fixation that Nectome uses is cheap to sustain. We will maintain a temperature around -30°C, above the “danger zone”, and keep preserved people in a liquid state for the long-term.1 That’s colder than your kitchen freezer, but typical in many biomedical applications. Instead of relying on deliveries of expensive, consumable coolant, we can buy a mass-manufactured freezer from any of a wide range of commercial suppliers. For us, the more likely scenario of failing warm is much less destructive than failing cold. In the worst case where we have a total equipment failure including our backup generators, or we go bankrupt and have to transport the preserved people to a companion facility, even a few days transport at room temperature is not damaging to ultrastructure.2 Overall, Nectome-style preservation is a much simpler and more forgiving endeavor than, for instance, storing frozen embryos.

The resilience of aldehyde-based fixation also unlocks the novel possibility of using permafrost. While our business model is currently based on having a dedicated, supervised facility, permafrost is an option that some people find appealingly geopolitically robust, and a nice method of last resort. The ground layer in parts of the Arctic and Antarctic never thaws year-round; a preserved person placed there in permafrost would maintain adequately low temperatures for centuries without any human intervention at all.

I hope Nectome itself survives for a long time, but in the event of tail risks such as economic collapse, catastrophic societal upheaval, or bankruptcy without recourse, aldehydes do give us permafrost as a lifeline. Our final commitment as an organization may be to transfer our preserved people to permafrost.3 While some catastrophes would happen too quickly to react to, many would be handleable in this fashion.

My question to you: if you had to take care of preserved people as cheaply as physically possible for the long term, assuming the temperature must be between -25°C and -35°C for 99% of the time over 100 years, and not between -36°C and -99°C for more than 48 hours over 100 years, what would you do? I think permafrost is the best option here, but where would you choose exactly, and why? Or if you have a better idea than permafrost, please let me know!

Priced to thrive, run on endowment

A second source of risk is the funding model: who pays for preservation? How much should you charge? How do you cover the cost of long-term cold preservation for the indeterminate future? How do you weather challenges like inflation over long time scales? What happens if we get sued?

Let’s start with recurring costs. We’re dealing with a situation where we want to disburse funds over a long period of time, and for predictable sources of expense – mainly refrigeration. Like other organizations faced with this shape of situation, notably universities, graveyards, pension funds, and our longest-lived cryonics companies, we choose an endowment model.

In this model, part of the up-front payment is placed in an endowment, where it is invested in diverse, resilient assets and managed by financial experts hired for this purpose. In this way, the interest gained on the investment beats the exponential attrition due to inflation, which would otherwise wipe out most fixed investments. And while economic upheavals are certainly a risk for the endowment model, we think that investing prudently and diversely is our best option.

I think that Alcor, graveyards, etc got it right: if you have fixed costs you need to fund for a century then you can do it with an endowment. There are other approaches we’ve contemplated—for example we know that asking surviving family members to pay on an ongoing basis tends to fail within a few years. Another option is eventually funding preservations through Medicare, and I consider this a useful future direction, but it’s not on the table currently. Right now, the endowment model has a proven track record for predictable expenses over long timeframes, and I see no reason to re-invent the wheel.

A second piece of the model is that we plan to make a long-term care non-profit, to be run as a distinct organization from us at Necome which handles selling and performing preservation procedures. This separation helps ensure that in the event Nectome cannot sell enough cryopreservations to keep the lights on or if Nectome takes on costly legal battles, the people already in care and the endowment itself will be financially insulated. Alcor uses this model, and we think it’s a wise one.

Finally, there’s a question of setting the price for preservation. It’s pretty common, in cryonics, for companies to run at a loss and stay alive through donations and volunteer work. I understand why this happens: we’re all in this together, trying to get as many people as possible to the future. It would be wonderful to be positioned to provide preservations pro-bono or at the cheapest possible price. As we’re taking our first steps as a company, though, I worry that this would put us in a financially precarious position, leaving us less capable of weathering challenges, expanding our research, and ultimately making preservation into a global tradition that can reliably reach everyone.

For this reason, I think I can provide the best stability and safety for our customers by running Nectome as a for-profit business, turning a profit every quarter, and growing at a brisk but steady rate. As of 2026, some of the first targets on our list include a marketing budget to extend our reach, expansion plans to offer preservation in more places, and a war chest in preparation for when Nectome needs to fight legal battles or go to bat for the emerging category of preservation law and the rights of preserved people.

As we grow, I expect that scale will be a big part of our robustness to social and legal challenges—say, if some part of the protocol gets outlawed someplace. I try to be realistic and measured about our prospects, but I think there’s real hope for a future where jurisdictions compete to pass laws that accommodate a lucrative industry in preservation. I hope that one day soon people will plan on having a career in preservation, that the field will become regulated and respectable. Many different speedbumps are more easily handled with the kind of goodwill and political and financial capital we’re working to accumulate.

My question to you: if you needed to charge an up-front amount of money to keep someone preserved, assuming an amortized annual cost-of-preservation of $X/yr and ignoring the setup costs for the preservation but including room for a robust legal defense fund, how much would you charge? And how would you manage the money? Now’s a great chance to bring up options; I bet there’s some good ones I’m missing!

Allies who keep us honest and wise

How will we keep our quality standards high? What about competitors? What if we’re bought out by a larger company? What about our mental health? Basically, how can we keep ourselves from losing our way?

We have a lot to prove as an emerging startup with goals this ambitious and scientifically demanding. Fortunately, we’re not starting from scratch and we’re not working alone: we’ve surrounded ourselves with a team of skilled advisors—including scientists, business mavens, cryonics veterans—who are among the smartest people we know, and whose collective knowledge helps steer us right and keep us true to our values. Many of these people are understandably sensitive about being named, but I’ll name-drop our YC group lead Michael Seibel and neuroscientist Bobby Kasthuri.

Some of our community members, like Andrew Critch and recently Max Harms, have given generously of their time to come investigate what we’re doing with a skeptical eye. I’m enormously grateful for the spirit of scientific inquiry and citizen journalship in which they approached us; I consider that kind of rigor and respect to be one of the greatest gifts one human being can give another. I believe Max intends to write about his findings and opinions on his blog, and I’ll link his piece here once he publishes it.

We deliberately cultivate costly external validation, both to be transparent, and because it keeps our standards high. One of our goals is that, by pioneering radical transparency and sky-high scientific standards in this newly-forming field, we’re helping to set a standard for all who follow. One of the risks we’ve got our finger on is the prospect of being undercut by a competitor that is cheaper because they cut corners on quality and scientific validation—someone who’s offering slapdash preservation that costs less because it sacrifices quality standards in favor of snazzy advertising and fast talk. I hope that rigorous standards applied across the cryonics industry mean that the whole field can be our allies, pushing us to offer consumers a better, cheaper product.

Like any scientist working to expand the boundaries of their field, I’m constantly indebted to those who came before me, and I rely on the hard-won metis of cryonics veterans. I’m glad I don’t need to discover the pitfalls of ongoing family payments for myself, and that I can imitate Alcor’s holding company setup wholesale. Every time I talk to Mike Darwin about what he’s seen over the years, I learn something new about how to run Nectome.

You’re part of our community, too. Someone who’s preserved poorly can’t call up the Better Business Bureau and complain, so they need you to keep the field honest. Cryonics consumers should demand to see randomized samples at sufficient resolution to see synapses, prepared in animal models representative of the kinds of preservation clients actually receive, like Andrew Critch did. As cryonics becomes more mainstream, insist on good third-party regulation. You are entitled to receive the lifesaving services you pay for, not an inferior substitute.

In short, we’re not going alone, and we don’t intend to. We’re passionate about making sure preservation succeeds for us, too, and our friends and family. We’re radical about demanding external validation to calibrate our optimism.

My question to you: Check out https://www.brainpreservation.org/accreditation/, the BPF’s page describing the accreditation program it’s building. Do you find the steps they’re taking convincing? Sufficiently rigorous? Give us feedback please, either in the comments or to Ken Hayworth (kenneth.hayworth@gmail.com) directly.

Another question for you: If you were starting a preservation company and were worried about keeping yourself honest, how would you set it up? What sorts of advisors would you want to have?

Proactive about laws and culture

What if they make preservation illegal in our jurisdiction? What if we get sued? What if we never get any kind of scale?

Preservation can seem weird to people right now. It occupies a strange and illegible position adjacent to the medical landscape, leaving its practitioners vulnerable to legal attacks and social opprobrium. I won the Brain Preservation Prize for large mammals in 2018, but it took almost another decade of innovation to devise a method legal to use on humans.

Nectome’s preservation has a lot of social and logistical advantages over previous cryonics approaches. Our cases are planned, opt-in procedures; we significantly reduce the last-minute chaos of cross-country phone calls, relatives questioning the patient’s wishes, hospitals attempting to restrict access. Because we’re physically near all our clients as legal death occurs, we have a good opportunity to establish clear consent, and can avoid ever being in a position where we have to disinter someone’s remains.4 Relatives have a chance to say farewell to their loved ones, and we can speak with them in advance about what to expect from the preservation process.

Another social advantage we can offer is compatibility with ordinary funerals. When I’ve worked with donated human cadavers, the results have been something I’d be happy to show to their families: the surgical incisions are easily covered by clothing and other techniques, and the person can rest peacefully at room temperature for weeks without issues. People I speak to feel very positively about this, and I’m hopeful that it lets us spend fewer weirdness points. I’d like to smoothly integrate with the existing funeral industry, just like with the medical and legal systems.

We’ve taken care to operate within a convenient and sensible legal jurisdiction. This is why we’re based in Oregon, even though I anticipate many of our early clients will be from California. Oregon’s medical aid-in-dying (MAiD) law is the oldest in the US and enjoys a strong local base of support.

One way a preservation may fail after the fact could be if the preserved body is autopsied, which typically destroys the brain. Our model is protective here: when someone uses MAiD, their death is declared by their attending physician, and their underlying terminal illness is listed as the cause. The legal system considers their death to be a natural one, and the medical examiner has no interest in investigating further because the person’s death has already been documented and was expected; generally they’re interested in unexpected / exceptional deaths.

Even with all of this, I’m aware that we face a great deal of uncharted legal territory, especially as we hope to expand beyond the relatively small scope of prior cryonics organizations. I consider it our job at Nectome to map out that territory, and this is why we’re building our own regulatory framework to fill a legal void. Right now we’re working under scientific research laws, but one of the goals at the top of my long-term list is carving out a new, proper legal niche for preservation.

I take inspiration here from birth doulas, who have historically operated in a similarly underregulated area. Doulas built their own regulatory standards and agencies, and many states have chosen to simply legitimize those agencies, or to adopt standards heavily informed by theirs. For instance, in Oregon, doulas may complete one of eight approved training programs in order to receive Medicaid reimbursement. I imagine a world where Medicaid offers to reimburse preservations certified by the BPF, with preserved people considered to be in a “chemically induced long-term coma” instead of classified as scientific research samples.

My question to you: Imagine you’re running Nectome, and you’re launching your post-mortem preservation program. What are you most worried about in terms of social and legal issues, and what would you do to address them early on?

S-risks

What if it feels like something while being preserved? What if the world changes and the future wants to revive and hurt preserved people? What if society collapses? These are all questions I’ve heard, here and elsewhere.

With regards to what it feels like to be preserved, I can with high confidence say it feels the same as DHCA, and that’s nothing at all. You need action potentials to think, and they’re not happening during preservation because of the dual effects of cold and crosslinks.

On the other hand, I can’t out-of-hand refute the risk of the future being very unpleasant, either because of takeover by a hostile AI or some other mechanism. The best solution I’ve come up with to help mitigate this risk is to very carefully record the preferences of everyone who we preserve and offer to cremate them if we anticipate that the chain of custody is likely to become compromised. Around half of people in my experience say that they would like to be cremated if we are going to lose chain of custody,5 or under some other condition, and the other half want to be preserved at all costs no matter what.

If it seems like things are deteriorating, and despite our best efforts we will lose control of the people we preserve, it may be that the last act of Nectome is to bury half of them in permafrost (according to their wishes) in an undisclosed location in hopes that someone will care later, and cremate the other half as they requested. It’s not something I’d ever want to do, but if I can create the safety for people to choose preservation today by promising to maybe cremate them in the future, I think it’s the right thing to do. I hope this means that someone preserved by Nectome is only subject to the same ordinary danger of very sudden S-risks that you and I are subject to today.

My question to you: Can you think of another way to mitigate S-risks for people being preserved today? Under what conditions would you like to be cremated after you were preserved?

Towards the future, with optimism and care

There is some faith in an organization that only comes with a proven track record of longevity. At the same time, rationalists can do better than reference-class forecasting. What Nectome can offer you, today, is an organization built on the wisdom of previous cryo attempts, and a set of unprecedented advantages against a variety of the most-likely failure modes on our list. We’re also thinking about long-tail risks and how we can address them.

One of the most important things at this tender stage is that we’re trying to become resilient at scale. There’s a lot that can kill a small company that a large company can weather with ease. We’re working daily to reach more people. Pre-sales are doubly valuable to us in this project: they contribute directly to our bottom line at a critical time in our company’s development, and they help us secure more investment.

I’ve asked a lot of questions here, and I really do care about your answers. My commitment to you is that I’ll read and respond to every comment posted here in the next two weeks, within three days, barring anything super unexpected on my end.

There’s no better time to influence how Nectome implements its preservation program, and I’m really looking forward to hearing your thoughts. Let’s make this a beautiful community effort.

In Ted Chiang’s short story Exhalation, a race of aliens have brains which run on compressed air, performing computations and storing information in elaborate arrangements of hinged gold-foil leaves. The leaves are held in position by a constant stream of air flowing through the brain’s tubules, encoding alien thoughts and memories. That ephemeral suspension pattern is the whole self—any alien whose supply of compressed air runs out is reduced to a catatonic state, all of their memories erased as the gold-foil leaves hang limply down. Even if air pressure is restored, the original information is lost for good. The person can never be recovered.

If this was how brains worked in our world, I’d be working on a very different kind of preservation. I might need to throw my hat in with the longevity researchers, or try to invent some kind of relativistic time-dilation bubble. I think we got lucky, though: when we look at electrical blackouts in the human brain, we observe something much more convenient.

The lady in the lake

In 1999, a Swedish radiologist named Anna Bågenholm fell into a frozen lake while skiing and became trapped under an eight-inch-thick layer of ice. For forty minutes, she struggled to breathe from a trapped air pocket before finally losing consciousness. At that point, her breathing stopped, her heart stopped pumping blood, and her brain went dark as electrical activity ceased—not like the quiet of sleep or even a coma, but complete electrocerebral silence. And then it took nearly an hour after that before rescuers managed to pull her body out of the water.

But this was not the end. Her rescuers airlifted her body to a hospital where—after two and a half hours with zero heartbeat—doctors attempted to carefully rewarm her. The operation took nine hours, but in the end, she survived. Even more remarkably, she made essentially a complete recovery, with no lasting brain damage save for the loss of some immediate short term memory, and no lingering problems save for some nerve damage in her hands and feet.

So a person who fell into a frozen lake, spending an hour with zero vital signs and a core body temperature of 57 °F/13.7 °C, survived the experience. The mishap was a freak accident, but the astonishing fact that recovery is possible tells us something about how brains work. Bågenholm’s case should already make us suspicious of any theory where—like the unfortunate gold-foil leaves in Chiang’s pneumatic aliens—the ephemeral live activity of the brain is load-bearing for memory and personal identity. This situation looks like the sort of thing you’d expect to observe in a universe where brains can safely be turned off and back on again. Whatever consequences Bågenholm may have suffered from her accident, she certainly seemed to emerge with her memories, cognition, and personality intact.

Using cold to save lives: DHCA

How is such survival possible? Of course, at ordinary warm temperatures, we can only go a few minutes without oxygen before suffering lasting catastrophic damage—hence the debilitating consequences of heart attack and stroke. But cold-water survival, which has been documented since ancient times, is another story. It turns out that a warm, oxygen-starved brain quickly begins to damage itself. While you’d ideally like your brain to have all the oxygen it wants, the next best thing is to avoid trying to run it—just like you’d power off your phone if you spilled a glass of water on it. It turns out that cold temperatures (about 15-30°C) are very effective at powering down brains in this way.

In fact, once you know the phenomenon exists, powering down brains turns out to be a useful technology—specifically for brain and heart surgeons whose operations depend on being able to work on a brain or heart while it is temporarily offline. The heart does not try to pump blood, the brain does not spark with electricity, and yet the body does not suffocate from the resulting lack of oxygen. Hence the technique of hypothermic circulatory arrest (HCA) was developed.1 Before an operation, surgeons lower the body’s temperature until circulation stops, usually targeting 20-28°C (moderate hypothermic circulatory arrest, MHCA) or in some cases as low as 14-20°C (deep hypothermic circulatory arrest, DHCA). This extreme cooling buys a window of time in which all normal vital signs are suspended—heartbeat stops, breathing stops, the brain becomes quiet—and the delicate surgery can take place. After the procedure is complete, the patient is carefully, slowly warmed and resuscitated, and they return to everyday life.

Hypothermic circulatory arrest provides cerebral protection during an extended period without oxygen or blood flow. For this reason, it has become the standard of care (Chau, 2013) for heart and brain operations since it was developed in the 1960s: for example, over 7,000 patients in the US underwent hypothermic circulatory arrest procedures between 2017 and 2021.

So how do patients fare afterwards? Do they survive with their memories, cognition, and personalities intact? In fact, in addition to the anecdotal experiences of patients and surgeons in the field, there’s plenty of literature evaluating the effects of DHCA on cognition. For example, Stecker et al. (2001) (Part II) survey 109 patients immediately after DHCA and find that 75% are aware, oriented, and neurologically normal. This doesn’t seem bad, among a population of very ill and immediately post-operative people, several of whom suffered strokes before or during the procedure.

More to the point, Percy et al. (2009) studied people in high-cognitive professions who underwent DHCA. Included in the group were “physicians, lawyers, doctorates, clergymen, artists, musicians, accountants, and managers”. The researchers interviewed both patients and their close family members, asking what differences they noticed before and after the surgery. The researchers found “excellent preservation of cognitive function after surgery, according to both patient and informant responses,” arguing that “although subtle deficits after DHCA might hide in individuals with less intellectually demanding professions, it is unlikely that substantive deficits could remain undetected in our high cognitive needs group.”

I still remember the first time I ever heard about DHCA: a brief digression during a TA session that was part of Sebastian Seung’s Intro to Neuroscience class at MIT, 2009. I still remember that day, because learning about DHCA was literally life changing for me. I learned that people can be “shut down” by cold, that they don’t have any appreciable brain activity in such a state, that this was still being used in hospitals routinely for tricky heart surgeries! For me, DHCA was one of those things that, once you see it, even for a moment, your life can never be the same again. I left that TA session in a haze. I hope to share some of that excitement with you today.

Electrocerebral silence

As a technical aside, I want to dive into the term electrocerebral silence—the electrical-blackout phenomenon observed in brains under hypothermic circulatory arrest. Although in cooled brains, electrical activity shuts down to the point that it’s undetectable on a standard EEG (unlike the gentle characteristic waveforms of an anesthetized or unconscious brain, electrocerebral silence looks like a total flatline; see Mizrahi et al. 1989.), the point isn’t the total absence of electricity. Brain cells, being bags of ions, may still occasionally emit tiny, sporadic sparks. The point is that they are totally disrupted in their ordinary electrical behaviors, unable to perform anything like normal synaptic computations (Volgushev 2000), and operating at levels so low they are invisible under EEG.

Stecker et al. (2001) tried deliberately super-stimulating neurons in chilly hypothermic brains, inducing evoked potentials by stimulating the wrist using a current 10-50x larger than a normal nerve signal. They found that even these oversize pulses petered out before reaching the cortex, indicating that the signaling pathways through the deep brain had been disrupted. The neurons had lost their ability to transmit information.

Cool them even further, and you can eventually knock out the ability of individual neurons to fire at all, even when artificially stimulated. The exact failure temperature varies by neuron, but averages around 12°C, and gets as low as 4°C (Girard and Bullier, 1989). Notably, 4°C is a temperature from which humans have recovered (Zafren 2020).

In short, I’d argue that in a person undergoing routine HCA, the occasional solitary neuron may send off sparks, but it’s clear these chilled, oxygen-starved neurons are almost entirely silent, are unable to communicate with each other over long distances, and that the ordinary dynamics of electrical cascades in the brain—and whatever information those dynamics held—have been totally disrupted.

Known unknowns

When I look at the state of the evidence, I find it implausible that we live in the inconvenient world of Chiang’s aliens. Instead, I seem to observe a world where the electrical cascades in the brain can be disrupted and zeroed out, but as long as the structure is intact, latent cognition remains intact. (For what it’s worth, “memory is structural” is also the conventional view among neuroscientists.)

This is why Nectome has put so much energy into preserving nanostructure in exquisite detail. There’s a lot we don’t know about the human brain, but whatever secrets it holds, the evidence points to them being stored in its intricate physical structures. We can’t decipher them yet—but we can make sure the structure is right there, ready for the future.

Extraordinary claims require extraordinary evidence. In my previous post, “Less Dead”, I said that my company, Nectome, has

“created a new method for whole-body, whole-brain, human end-of-life preservation for the purpose of future revival. Our protocol is capable of preserving every synapse and every cell in the body with enough detail that current neuroscience says long-term memories are preserved. It’s compatible with traditional funerals at room temperature and stable for hundreds of years at cold temperatures.”

In this post, we’ll dive into the evidence for these claims, as well as Nectome’s overall approach to cultivating rigorous, independent validation of our methods—a cornerstone of the kind of preservation enterprise I want to be a part of.

To get to the current state-of-the-art required two major developmental milestones:

• Idealized preservation. A method capable of preserving the nanostructure of the brain for small and large animals under idealized laboratory conditions. Specifically, could we preserve animals well if we were allowed to perfectly control the time and conditions of death?
  
  This work (2015-2018) resulted in a brand-new technique—aldehyde-stabilized cryopreservation—which was carefully independently vetted by Ken Hayworth of the Brain Preservation Foundation over a three day-long marathon session during which I preserved a rabbit and pig under his supervision. After, he reviewed multiple samples from both brains with electron microscopy. I published Aldehyde-Stabilized Cryopreservation in Cryobiology, and won the small- and large-mammal prizes from the BPF as a result. With this work, we had an existence proof: preserving entire brains long-term in nanoscale detail was absolutely achievable, at least under laboratory conditions.
  
  

• Real-world preservation. A method capable of preserving the nanostructure of the brain under realistic conditions. Specifically, could we extend the laboratory method to work under the legal requirements and practical limitations that constrain real-world human cases?
  
  Adapting the technique to messy real-world conditions (2018-2025) took significantly more development, resulted in a bunch of insights about what is feasible and infeasible for human preservation, and shaped our entire approach to preservation going forward. In one memorable instance, once we finally had a technique that worked to our standard of rigor on pigs, we once again put it to the test in a marathon live demonstration. Andrew Critch, cofounder of the Survival and Flourishing Fund, personally witnessed the preservation of a rat under conditions that mimicked human preservation; the resulting brain samples were imaged in consultation with a microscopy lab at UC Berkeley and Professor Kasthuri at U Chicago. As a result of our demo, he recommended us for an investment, which we’ve since received. The real-world technique has been submitted as a preprint, Ultrastructural preservation of a whole large mammal brain with a protocol compatible with human physician-assisted death.

The rest of the post is dedicated to unpacking these results.

Five quick notes as we begin:

• By popular demand, this post is specifically about nanostructural preservation quality—achieving a level of detailed preservation throughout the entire brain and body such that synapses are traceable to their originating neurons and subsynaptic details are retained as well as traditional fixation methods used in neuroscience research. I’ll postpone the argument that whole-body nanoscale preservation is sufficient for future revival, as it deserves its own post.

• A draft version of this post has been reviewed by Ken Hayworth, president of the Brain Preservation Foundation, and he signed off on it as: “an accurate description of the Brain Preservation Foundation, its history, Ken’s personal motivation, and the results of the BPF’s two preservation prizes”. I’ve not substantially modified it since.

• A draft version of this post has been reviewed by Andrew Critch, cofounder of the Survival and Flourishing Fund, and he signed off on it as: “an accurate description of his visit to Nectome to evaluate their preservation technology, and the later results.” Again, it’s not been substantially modified since.

• Conflict of interest note: During grad school, I worked as a volunteer for the Brain Preservation Foundation for about a year. After learning more about brain preservation, I decided to quit as a volunteer and enter the prize myself, with Ken’s approval.

• You may notice that some of the references I cite throughout this post attribute my work to my deadname, Robert McIntyre. Today I go by my chosen name, Aurelia Song.

In the lab: Ken Hayworth and the BPF

What is the Brain Preservation Foundation?

Ken Hayworth is a neuroscientist currently working at Janelia Research (part of HHMI, the Howard Hughes Medical Institute). In 2010, Ken started the Brain Preservation Foundation and launched the Brain Preservation Prize as a challenge to the neuroscience and cryonics community. He wanted to see researchers provide evidence that their preservation could work according to neuroscientifically reasonable standards.

As a connectomicist, Ken is used to looking at 3D models of brain tissue created with electron microscopy. These models are scanned from brains preserved with the kind of high-quality fixation that’s been standard in neuroscience for many years. After much serious thought about neuroscience, Ken has come to the conclusion that this level of physical preservation is overwhelmingly likely to capture the information necessary to restore a person in the future, and I’m inclined to agree. Again, I’ll get to this in an upcoming post.

But the electron micrographs coming from the cryonics community didn’t look like what he normally saw in the lab. There was no 3D analysis, just single frames. Worse, the tissue was severely dehydrated, making it difficult or impossible to tell whether the tissue was traceable, that is, whether each synapse could be traced back to its originating neurons.

To Ken and to me, this is an enormous issue. There are many ways a brain can be rendered untraceable, and comparatively few that preserve its structure. In the absence of evidence to the contrary, we have to default to the assumption that a brain is not traceable. That, in turn, calls into question whether the information preserved in the brain is adequate.

In addition to challenging the cryonics community, Ken wanted to extend a challenge to the neuroscience community. He hoped that, making use of their advanced protocols for preparing and analyzing brain tissue, they could design a technique to preserve people for later revival.

Ken was inspired by the successful Ansari X Prize to issue his challenge in the form of a prize. He raised $100,000 from a secret donor,1 and set out the prize rules: brains had to be preserved in a way that rendered them connectomically traceable, and had to be preserved so that they would very likely last for at least 100 years. There was a small version of the prize for a “small” mammal brain (think rabbit, mouse, or rat), and a “large” mammal brain (pig, sheep, etc) would win the whole thing.

I can’t overstate how influential the Brain Preservation Prize has been in advancing the field of preservation research. That $100,000 inspired me to build my protocol and led to millions of dollars of investment in better preservation. I’d love to see more scientific prizes; I think they help young people in research labs justify spending resources on important projects they’re passionate about. A young researcher, like me back in 2014, can go to her superior and say “it’s not just a personal project, it’s for this prize.”

A protocol that works under ideal conditions: Aldehyde-Stabilized Cryopreservation, 2015

When I started seriously looking into preservation techniques, it seemed to me that cryonics and neuroscience had opposite problems. Neuroscientists could almost instantly preserve a brain using aldehydes,2 but didn’t have a long-term strategy to keep that brain intact for a hundred years or more. Cryonicists, meanwhile, struggled to avoid damaging a brain when they perfused it with cryoprotectants, but knew how to cool a perfused brain to vitrification temperature and keep it there indefinitely.

The obvious solution was to combine the two methods. I could use fixation’s remarkable ability to stabilize biological tissue, buying time to infiltrate cryoprotectants into the brain slowly enough to avoid the crushing damage caused by rapid dehydration. Then, it would be safe to vitrify the brain for long-term preservation.

It took me about nine months to iron out all the details. The most difficult part was figuring out how to get cryoprotectants past the blood-brain barrier: it turned out that even very extended perfusion times, on their own, are not adequate to prevent dehydration. Eventually, though, I got the technique to work on rabbits (the “small mammal” model I was using). Modifying the protocol to work for pigs took me a single day and worked on the first try. I published the results of that research, Aldehyde-Stabilized Cryopreservation, in Cryobiology, the first step towards winning the Brain Preservation Prize.

Independent Verification by the Brain Preservation Foundation

The next step towards the prize required direct verification by the BPF. If you’re interested, you can read their full methodology here.

At this time, I was working at 21st Century Medicine. Ken Hayworth flew out to my location and joined me for a marathon three-day, dawn-to-dark session, during which I preserved, vitrified, rewarmed, and processed a rabbit and a pig. Whenever Ken wasn’t personally observing the brain samples, he secured them with tamper-proof stickers to preserve the chain of custody. When I had finished preparing the samples for electron microscopy, Ken personally performed the cutting and imaging of the samples back at Janelia.

This was a level of rigor I’d never observed before, certainly far beyond the peer review for the Cryobiology paper. This is something I admire about Ken, and I was grateful for it here. Preservation is worth being rigorous about!

The BPF prepared images using high-resolution focused ion beam milling and scanning electron microscopy (FIB-SEM). This technology produces resolutions of up to 4 nanometers; Ken scanned the prize submissions at 8 nm and 16 nm isotropic resolution. Together with the 3D nature of the images, this is sufficient to examine a brain sample and determine whether the synapses (typically about 100 nm wide) are traceable.

Of course, imaging a whole brain is well beyond our current capabilities. Ken compensated for this by analyzing many samples, randomly chosen from different regions of the brains. The BPF released all of the images and the original 3D data files, and they’re still available today. I’ve included the pig brains below, with youtube videos showing the 3D imaging in full. Each sample is from a brain that was preserved, vitrified, and rewarmed.

Ken Hayworth was joined on the BPF’s judging panel by Sebastian Seung, a Princeton/MIT neuroscientist, author of the book I am my Connectome, and a major contributor to the FlyWire project. Together, they reviewed the 3D images, judged their quality, and traced neurons through the image stacks. In the end, they agreed that I had won the prize.

Relevant links:

• Small Mammal BPF Prize Winning Announcement

• Large Mammal BPF Prize Winning Announcement

• Letter of support for Aldehyde Stabilized Cryopreservation to be developed into a medical procedure

I present this as evidence that it’s possible to preserve large mammals brains in a traceable state, every synapse intact, and keep them stable for more than a hundred years (the ‘hundred years’ part we will address in a future post on the thermodynamics of preservation).3

But ASC is not the whole story, because it must be done pre-mortem. End-of-life laws throughout the world weren’t designed with preservation of terminally ill clients, and don’t allow ASC as an option. In order to create something workable, I had to either find a way to do preservation post-mortem, or work to incorporate ASC into end-of-life laws. I chose to make preservation work post-mortem.

In the field: Andrew Critch and the SFF

Making preservation work in the real world turned out to be conceptually easy. The original protocol needs three modifications to work post-mortem.

1. Cardiac arrest must happen quickly in order to avoid pre-mortem brain damage. We found that Medical Aid-in-Dying (MAiD) is required.

2. You must use blood-thinners before cardiac arrest.

3. You have to do the surgery fast. The perfusion needs to start less than about 12 minutes after death.
   

My dad used to tell me a story of a biology professor he had in college. The first day of class, the professor had everyone open their textbook and read the first paragraph in one of the last chapters. The professor then told everyone that it had taken him 30 years to write that paragraph. I now better understand how that professor must have felt. It took me nine months to create ASC. It took me nine years to modify it to work in our current legal context and write those three modifications above.

I won’t get into those nine years in this post. I do want to share an image, though, that I’m publishing here for the first time. As far as I know this is the best preserved whole human brain in the world, and it belongs to a 46-year-old man who died of ALS and chose to donate his body for scientific research. I perfused his body just 90 minutes post-mortem—much faster than typical emergency cryopreservation services, but well outside the twelve-minute ischemic window.

It is the best-preserved whole human brain I’ve ever seen. It is also—like every other human brain I preserved with any appreciable post-mortem delay—not traceable. It’s not a quality I (or the BPF) can accept. Looking at the degree of damage scares me.

I originally thought that humans might have a two-hour post-mortem preservation window. If that had been true, I would have probably worked to integrate preservation into hospices across the country. After reviewing the electron micrographs from animals and humans under various preservation conditions, it became clear that the hospice model was nonviable. We couldn’t wait for a person to die on their own timeline and only then begin our procedure. We’d need them to undergo a full process involving Medical Aid in Dying (MAiD)—and before we could promise any benefits from such a process, we needed to perfect it on animals.

It took a lot of refinement and expert consultation, but eventually we pinned down the twelve-minute window and blood thinner through a series of experiments on rats. We then streamlined the procedure so it could be done in less than ten minutes on pig carcasses, and finally demonstrated excellent post-mortem preservation in a pig model. We’ve just recently published the results:

Independent evaluation by the SFF

About this time, I was chatting with Andrew Critch, cofounder of the Survival and Flourishing Fund (SFF). Born from Jaan Tallinn’s philanthropic efforts, the SFF is dedicated to the long-term survival and flourishing of sentient life. They recommended $34MM of grants in 2025, including support for the AI Futures Project, Lightcone Infrastructure, and MIRI, among many others.

Andrew was interested in evaluating Nectome for an SFF grant. We talked it over and agreed on a third-party evaluation with real stakes: he’d travel to our lab in Vancouver, Washington to witness and evaluate a preservation first-hand, then bring the samples himself to an EM lab to scan them, and then ask a neuroscientist of his choice to review the sample quality. If he liked what he saw, he’d support our application to SFF’s grants team. If we didn’t live up to the quality we promised, he’d inform the team accordingly. (SFF uses a distributed grant-making process where each team member has a separate budget for making grant recommendations with substantial discretion.)

When Andrew arrived at our lab, we introduced him to our test rat,4 and he observed as I gave the test rat an injection of heparin (our blood thinner of choice), followed promptly by simulated medical aid-in-dying. He then timed us as I waited five minutes after the rat’s heart stopped, mimicking the time I would have spent performing surgery on a pig or a human.5

From there, we proceeded with the tedious 9-hour process: blood washout, fixation, and the slow ramp of cryoprotectants. Andrew watched from start to finish. It was late at night before the preservation was complete, and Andrew watched us remove the rat’s brain and perform a visual check for gross failures of perfusion. There were none.

At this point we could have simply placed the brain in cold storage and then handed off the tissue for further evaluation, but I wanted to demonstrate just how robust our current method is instead. I cut the brain into two hemispheres, put one in cold storage at -32°C (-26°F) as a demonstration of the effectiveness of the cryoprotectant at preventing ice formation, and put the other hemisphere in a laboratory oven at 60°C (140°F) overnight. Just as cold storage slows chemical processes, warmth accelerates them; twelve hours at 60°C is equivalent to, conservatively, a week at room temperature.

When we returned the next day, we sliced each hemisphere into paper-thin slices and Andrew spun up his quantum random number generator.6 He used it to randomly select four slices from each hemisphere for analysis. We sent him home with an introduction to Berkeley’s electron microscopy core facilities, which immediately started the week-long process of prepping the tissue for imaging including staining, resin embedding, and slicing into 90-nanometer sections.

After examining the electron micrographs and consulting with several neuroscientists, Andrew determined that our preservation was excellent, that the brain was connectomically traceable, and that both the “cold” and the “hot” slices were of near-identical preservation quality. He recommended us for a $550,000 investment, which we’ve since received.

We’d like to present this data to you as well. The overall dataset obtained from Berkeley was massive; a single image from one of our samples is around 5 GB and requires special software to view. I’ve prepared two representative images using deepzoom, here:

“Come with me if you want to live.” – The Terminator

“’Close enough’ only counts in horseshoes and hand grenades.” – Traditional

After 10 years of research my company, Nectome, has created a new method for whole-body, whole-brain, human end-of-life preservation for the purpose of future revival. Our protocol is capable of preserving every synapse and every cell in the body with enough detail that current neuroscience says long-term memories are preserved. It’s compatible with traditional funerals at room temperature and stable for hundreds of years at cold temperatures.

The short version

• We’re making a non-Pascal’s wager version of cryonics.

• Our method is an end-of-life procedure for whole-body, whole-brain human preservation with the goal of eventual future revival.

• Preservation occurs after legal death.

• Even without the near-term possibility of revival we can be confident that preservation actually works.

• We preserve the whole body, including the brain, at nanoscale, subsynaptic detail. We are capable of preserving every neuron and every synapse in the brain, and almost every protein, lipid, and nucleic acid within each cell and throughout the entire body is held in place by molecular crosslinks.

• It works by using fixative to bind together the proteins and cryoprotectants to prevent ice over the long term, and cold temperature to extend the stable preservation time period to centuries.

• We’ve won the Large Mammal Brain Preservation prize from the Brain Preservation Foundation for preserving animal brains, which involved examining the preserved synapses across many regions of the brain.

• Unlike previous cryonics methods that required extremely low-temperature liquid nitrogen coolant, our method is stable for months at room temperature and compatible with traditional funeral practices.

• Biology imposes a strict time limit for successful, real-world preservation: we’ve found that if you want high-fidelity preservation, you must start the procedure within twelve minutes post-mortem. This means that all of our procedures are planned, and we do not offer emergency preservation.

• We don’t yet have the technology to revive someone who has been preserved, but we do have the evidence to say that we preserve all the information that would be needed for revival.

• We’re agnostic towards revival methods: uploading, biological revival, or any other sort, and we think that regardless of method, our starting point offers the best chance.

• We’re offering limited pre-sales now.

“Maybe” isn’t good enough for me

A brief refresher: traditional cryonics uses two things to preserve people: cold to preserve the brain, and cryoprotectants to prevent the catastrophic damage caused by the formation of ice crystals. Unfortunately, cryoprotectants themselves crush neurons through osmotic effects, damaging the structure of the brain.

Traditional cryonics works in “emergency mode”, where cryonics organizations are first notified after one of their members dies, then attempt to preserve them in response, often with a delay of hours or even days during which time the brain is damaged. Traditional cryonics takes place after a “natural death” in most cases. However, natural deaths take a long time, and brain damage sets in well before legal death. For me, all this damage calls into question whether memories are really preserved.

The strongest argument for traditional cryonics is that any kind of preservation is better than nothing, and that cryonics is “not a secure way to erase a person“. This is true enough as far as it goes: certainly, no physical process truly “destroys” information. What we really care about with preservation is how accessible the information is and whether it’s still contained within a person’s preserved body or not. This is a really important question for me, so I ran the experiments myself and was not impressed.

I set out to build something that feels to me like less of a Pascal’s Wager. I want a preservation protocol that, according to our best theories of neuroscience, does work. At the same time, I wanted to craft an experience that normal people would be comfortable with – I want our parents and grandparents to be willing to come into the future with us.

The result is a protocol that my company, Nectome, has spent the past ten years developing. After years of experiments in the lab and in the field, learning about the complexity of end-of-life biology, and after refining our protocol to make it robust and repeatable for real people in real-world clinical settings, we are now ready. We’ve developed a whole-body, whole-brain, human end-of-life preservation protocol based on neuroscience first principles. We are capable of preserving every synapse and almost every protein, lipid, and nucleic acid throughout the whole body. Brains are connectomically traceable after preservation. Our preservation is so comprehensive that current neuroscience theories imply it preserves all relevant information necessary for future restoration of a preserved person.

Further reading: “Brain Freeze”, Aurelia Song, Asterisk Magazine

A preservation protocol that’s worthy of us

Cryonics in my opinion has had two main issues holding it back, both of which we’ve solved.

The Quality Problem: The first issue is that traditional cryonics methods haven’t been shown, even under ideal circumstances, to preserve brains well enough that they’re connectomically traceable afterwards. We solved this issue by adding crosslinks to the mix. In 2015 I published a protocol in Cryobiology using crosslinks, cryoprotectants, and cold to preserve animal brains with near-perfect quality. In 2018 I won the Brain Preservation Foundation’s Large Mammal Brain Preservation Prize using aldehyde-stabilized cryopreservation.

The Timing Problem: The second issue is with the emergency response model of traditional cryonics. Doing preservations as an emergency response and after a natural death causes damage independent of whatever protocol you’re using. Severe damage happens before legal death as a result of inadequate blood circulation and partial brain ischemia. Even more damage occurs post-mortem due to cell autolysis and other degradation pathways. Shortly after death it becomes almost impossible to completely perfuse brains (this is the problem that ended up giving us the most trouble).

We worked from 2018 to 2025 trying to solve the Timing Problem to our satisfaction, and eventually succeeded in creating a protocol that gave comparable results to our ideal laboratory version, but could be used in the real world. There’s a cost, of course, for this quality: we’ve learned that preservations must start within twelve minutes post-mortem after a quick respiratory death. That means preservations have to be scheduled in advance, and they have to be done in conjunction with medical aid-in-dying (MAiD).

The images above are taken from the BPF’s Accreditation page. On the left, you can see the pig brain which I preserved, winning the Large Mammal prize. The cellular structure is intact and it’s easy to trace the connections between the neurons. The right-hand image shows the damage caused by traditional preservation, even under ideal circumstances. Real preservation cases are far worse due to pre- and post-mortem brain damage. Maybe a superintelligence could reconstruct the structure – but it’s unclear whether the information to do so remains.

We’ve published a preprint of some of the most relevant experiments on bioRxiv, where we show we can get the same excellent quality we got in 2018, except now under realistic end-of-life conditions. We’ve also performed experiments which have undergone independent evaluation; we’ll discuss those in a subsequent post, but for now here’s a sneak peek:

This is a section taken from a rat brain preserved 5 minutes post-mortem in a manner that’s consistent with the surgical time we can achieve with pigs. All axons, dendrites, and synapses pictured are connectomically traceable. After preservation, we stored this brain at 60°C for ~12 hours before imaging! Click through for a “Google Earth”-style presentation of the whole slice, which is around 5 GB of data.

What does preservation look like for you?

In order to work within the limits of biology, Nectome does preservation exclusively as a planned, scheduled procedure. We do not offer an emergency response model because there is no emergency response model we could do which would meet our standard. To receive a preservation which meets our standard of care, terminally ill patients must plan in advance, travel to a preservation center, and use medical aid-in-dying.

Our business model is different than traditional cryonics: we sell transferrable preservations in advance instead of using a membership + insurance model. When you buy a preservation, you buy the ability to designate a person of your choice (including yourself) to be preserved. We will then work with that person to understand their preferences for preservation, the most important of which are:

1. Chain of custody: In the event of an impending loss of custody of your preserved body, such as major government changes, what do you want us to do? Do you want us to cremate you, or do you want us to do our best to make sure you stay preserved, even if it means we will no longer be in control of what happens later?
   

2. Method of revival: Do you want to restrict which revival methods may be used to restore you in the future? Nectome is officially agnostic on revival method. Do you want to restrict the use of destructive uploading to revive you? Wait for 100 years and then only do it if there’s not another option? Do it but only after 1,000 people have done it before you and liked it? This is a very personal question and we want to get as much information in advance so we can respect your choice.

We’ll be inviting clients and their families to stay for a few days at a beautiful preservation center in the peaceful Oregon foothills, where they can spend time together, say their goodbyes, and participate in any farewell ceremonies they choose. After the procedure the preserved person is stable for months at room temperature, allowing for a standard open-casket funeral in their home state.

In the long term, preserved people will be maintained at -32°C. In all cases, they will remain in a whole-body state; Nectome never does brain-only storage.

Conclusion

I’ve introduced here a new kind of cryonics which I hope will move the field away from Pascal’s wager and towards a rigorous discipline that becomes a mainstream part of end-of-life care.

We can preserve people following MAiD with a protocol that can preserve every synapse and virtually all biomolecules, throughout a person’s entire body. That’s good enough that our current theories of neuroscience say it does work to retain sufficient information about a person such that they could be restored with adequate future technology.

We know that our protocol doesn’t serve everyone, and we hope that continuing scientific and legal advances will allow us to preserve an increasing fraction of people. But it serves many people (most people don’t die suddenly!), and we want to offer something that verifiably works, not a shot in the dark.

We don’t yet have the technology to revive someone who has been preserved, but we do have the evidence to say that we preserve all the information that would be needed for revival.

Over the next posts in this series, I’ll go over the information-theoretic basis we use for preservation, the reasons why it has to be an end of life protocol, our hope for the long-term future, why this all still makes sense even given short AI timelines, and several other things.

In the meantime, below you’ll find several of the links in this post and descriptions of why you might want to read them.

I want you to live

Why did I spend the last 10 years of my life on this project?

We all start out life born in twin prisons: the gravity well of the earth, keeping us on a tiny speck of dust compared to the wider universe beyond, and the limit of our natural lifespan, confining us to a tiny sliver of the universe’s grand history.

When preservation becomes a new worldwide tradition, even before revival is technically possible, it will expand peoples’ personal planning horizons. I expect to see people start 1,000 year projects believing they will personally see the end result. I’d like to see what they choose to make.

I believe that Preservation is for everyone and that the future loves you and wants to welcome you back with a desire that can’t be conveyed with words on a page. Let’s get there, together.

• Our whitepaper detailing how preservation will work and why we think it works. https://nectome.com/personal-preservation-whitepaper.pdf

• Our recently-published work preserving pigs under real world end-of-life conditions. https://www.biorxiv.org/content/10.64898/2026.03.04.709724v1

• The paper describing the technique that won both Brain Preservation Prizes: https://www.sciencedirect.com/science/article/pii/S001122401500245X

• Brain Preservation Prize large mammal announcement: https://www.brainpreservation.org/large-mammal-announcement/

• “The Case for Glutaraldehyde” an analysis of why fixation likely preserves sufficient information about a person for future reconstruction: https://nectome.com/the-case-for-glutaraldehyde-structural-encoding-and-preservation-of-long-term-memories/

• Brain Freeze, an article in Asterisk Magazine talking about the problems facing traditional cryonics: https://asteriskmag.com/issues/10/brain-freeze

• The BPF’s plan for accreditation. Nectome hopes to become fully accredited and begin preserving people this year. https://www.brainpreservation.org/accreditation/

Our protocol is capable of preserving every synapse and every cell in the body with enough detail that current neuroscience says long-term memories are preserved. It’s compatible with traditional funerals at room temperature and stable for hundreds of years at cold temperatures.

Nectome has a very straightforward “buy a preservation, get a preservation” model. We don’t do memberships, insurance, or lots of red tape. You sign one document, you send us money, and you’re entitled to one preservation. You can use it for yourself or a loved one, and you don’t need to decide at the time of purchase. If the person ends up not being eligible, use it for someone else or resell it.

Currently offering full-price sales at $250k

As of 5/11/2026, we’re currently only offering full-price sales. Watch this space for future deals for select communities.

How to buy

Reach out to us at hello@nectome.com to discuss purchasing for yourself or a loved one.