Less Dead
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.
We’ll be hanging out in the comments section for the next several hours to engage with your questions. We also have a Manifold poll, embedded near the bottom, about what next post would be most valuable to the community.
“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[1]. 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 cryopreservation, 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 our 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 transferable 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:
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?
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.
When it’s time, we’ll invite 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 will become 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
Our work published last week preserving pigs under real world end-of-life conditions. https://www.biorxiv.org/content/10.64898/2026.03.04.709724
Our 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/
I’m looking forward to talking with you all in the comments. I’ll be around for a while once this post is up. There’s a lot to discuss! Vote for what we should cover next:
“Connectomically traceable” means that each synapse can be physically traced to its originating neurons in a gigantic 3D map. For more info, I like Sebastian Seung’s TED talk. ↩︎
Vote of confidence: I have signed up with Nectome and am keeping my eyes open for ways to support their work.
Thanks! Can you say a bit more about how they got your vote of confidence? I’m intrigued but don’t know the people involved and don’t know anything about the relevant physics / chemistry / neuroscience.
Sure thing. A friend who had met with the team and was impressed offered to set up a meeting. When I met them I was impressed by detailed answers to both my questions around the science and the questions around the incentives that surround such an org, and what long term viability looks like. Often when I speak with founders I have to be a little forgiving and see whether I think their strengths will render them enough resources and non terrible incentive environment to be able to pay for their weaknesses. In the case of Nectome I got the sense they are paying attention to past failures and not falling prey to too much hopeful thinking. I think this is reflected in the scenario analysis of the post.
The particulars that got me interested:
I have long been sympathetic to fixation over cryo bc I believe org risk is very high on some basic actuarial base rates for orgs. If my body can be chucked in a borehole in permafrost at a geologically inactive site and left there that would be ideal IMO. People who imagine themselves revived in a repaired version of their biological body seem to think full body cryo has a better shot for hand wavy reasons afaict.
compatible with normal funerals, so dramatically lower spending of weirdness points and religious objections. I think this means it can scale about 2oom more than cryo at least.
the level of damage by this process (as performed by random assay from third parties) appears to be less than the levels of damage in cases of revival from hypothermic drowning, such people have had (mostly?) complete recovery of personality and memories afaik.
competence of the team.
the much higher feedback cycle over cryo. Other preservation groups are not actively doing electron microscopy nor lab animal experiments afaik.
I don’t know a ton about why aldehyde fixation is able to preserve such fine structure, but the data look reasonable to me.
My reaction is more mixed than Romeo’s, but I see enough promise that I’m leaning toward buying their $100k full preservation pre-sale.
I’m moderately confident that their technology is better than Alcor’s. I haven’t investigated it as carefully as Romeo has. I’ve paid enough attention to this field that I think I would have heard of significant problems if people saw them, and there seem to be no criticisms of its suitability for uploading.
Aurelia seems smart. I have some concerns about her business skills.
She tried to get me to invest in Nectome in June. I declined, evaluating it primarily on Nectome’s financial prospects. Her revenue forecasts seemed wildly optimistic, disagreeing with my impressions much more than is normal for a startup.
But this winter I’ve been shifting to thinking of doing something to support Nectome financially, in order to increase the chance that they’ll be available if I need them. This shift is largely a result of increased wealth from AI-related investments, not any new information about Nectome.
Aurelia, could you estimate the minimum revenues required for Nectome to maintain its ability to perform preservations?
Note that the 2015 paper that Aurelia mentioned was one that she co-authored with Greg Fahy. Fahy is highly respected among cryonicists for, among other things, his role in persuading the cryobiology community to tolerate cryonics. Fahy has also pioneered a treatment that seems to partially reverse aging (that company needs and deserves more investment).
Note that Aurelia also works at Michael Andregg’s Eon Systems, which has recently uploaded a fruit fly.
Hmm, that last line actually concerns me. I don’t have enough knowledge of the subject matter to be able to know for sure, but I got the impression that the fly upload announcement was misleadingly exaggerated, acting as though they had gotten fly-like behavior from a brain upload when in reality they used reinforcement learning to create the behavior they desired. If she’s associated with them, I worry that these preservation announcements are similarly misleading.
No? Where did you get that from?
Can’t find the post that mentioned reinforcement learning again, but for example from the announcement on their website:
Hmm, the announcement on X does state explicitly that it wasn’t reinforcement learning. But this tweet from the president of the Brain Preservation Foundation certainly thinks it was misleading. Not sure what the real story is at the moment.
So first off, I want to say that Ken Hayworth is one of the scientists I respect most in the world, and he cares a lot about precision in language and making sure that nothing gets overstated. I’ve actually asked him to be heavily involved in Nectome’s certification process, and I think his careful approach will bring a lot of rigor to that. I do think his tone with Michael was a little harsh here, and he’s erring on the side of judging a twitter one-liner like it’s a scientific paper.
I helped found Eon and am currently one of their advisors, and I think the fruit fly upload situation is one of those things that’s like this comic:
Now, I’m actually thrilled to talk about the flywire situation, because while I think there’s been some miscommunication about it due to the standard science hype cycle and the way twitter is, and I think the object-level facts are a really cool result that you guys will appreciate.
The Eon simulation is what I’d describe as a “partial upload”, using leaky integrate and fire neurons. It’s built on Philip Shiu’s work in fruit fly brain modeling (https://www.nature.com/articles/s41586-024-07763-9). Philip has been part of Eon for about a year now. The work in the tweet is showing off how Eon took Philip’s model and added a body and environment to it to make it more embodied. Check out Alex’s description here: https://x.com/alexwg/status/2030217301929132323. Is this a full fruit fly upload? No. It’s not simulating the neurons in the fruit fly’s body directly (because we don’t have them), instead it’s looking at the brain and reading out approximately which way the brain wants to move the body, then puppeteering the simulated body in the same direction. So the simulated brain is controlling the body, but in more of a “prosthetic” sense, or like how a person controls a character in a video game. The simulated brain is also getting visual information from the simulated environment, so when it turns left and there’s a thing there, that changes the pattern of information going into its simulated eyes appropriately. The brain simulation is very simple compared to how the fruit fly brain works in real life, and incomplete, but does still reproduce many interesting behaviors in spite of all the simplifications. I’ve run the simulation on my laptop in an earlier form, I can go into more details in a future post if people are interested.
I think Eon / Phil’s work is a really cool result, and the fact that it works at all is to me very impressive. It could have been the case that when we scan connectomes and simulate them with very simple mathematical models, it didn’t do anything even remotely resembling actual animal behavior. If that had been the case, I’d be slightly more inclined to say that there’s important and subtle chemical information, not reflected in the kind of information you can get with an electron microscopy that you need in addition to a connectome to get an upload working. It wouldn’t move me on brain preservation working by very much, because almost all proteins are preserved by aldehydes, but it would move me somewhat on how easy I think full uploading in Ken’s sense will be. I take the recent partial fruit fly uploading work as weak evidence that brains are going to be fairly easy to simulate, and that much of the necessary detail is inferable from the geometry of the connectome.
Over the course of the next couple of blog posts, I’d like to provide all of you with some solid resources for evaluating what we’re doing at Nectome, and let you form your own judgements from there.
Happy to answer any further questions about Flywire. I do think it’s a really awesome result, and I was pleased that the Eon team put together that video. If you guys are interested, we could even incorporate a more in-depth discussion of the project as a post in our sequence here.
I did a shallow investigation of this and my conclusions were:
The text on EON’s frontpage, Michael Andregg’s tweet thread, and Alex Wissner-Gross’ post seem pretty misleading in practice while this tweet from Kenneth Hayworth is more representative of the situation. I think EON’s blog post on this is not misleading while the front page of their website is.
EON / Michael Andregg / Alex Wissner-Gross mostly don’t make straightforwardly false claims, but nonetheless much of their communication (though not all of it!) is (predictably) misleading.
I think the 91%/95% accuracy claims are pretty misleading, though I don’t have the expertise to confidently adjudicate this.
The EON front page says “No hand-coded behaviors. Just brain structure producing brain function.” In fact, the walking gaits and grooming leg motions come from NeuroMechFly motion primitives. Thus I think this is basically false rather than merely being misleading.
The post from Alex Wissner-Gross is generally less misleading, but contains some pretty misleading text (“If a fly brain can now close the sensorimotor loop in simulation, the question for the mouse becomes one of scale, not of kind.”, “Watch the video closely. What you are seeing is not an animation. It is not a reinforcement learning policy mimicking biology. It is a copy of a biological brain, wired neuron-to-neuron from electron microscopy data, running in simulation, making a body move. The ghost is no longer in the machine. The machine is becoming the ghost.”).
I also think their prognosis about the situation and implicit predictions seem wrong, but this is more like a normal disagreement.
This isn’t representative of much progress towards uploading. I would be impressed by non-overfit versions of: “you took an actual living fruit fly, had it learn a behavior that’s among the most sophisticated behaviors a fruit fly can learn, then you uploaded it, and the upload displayed the same behavior”. I would also be somewhat impressed by the same thing for C. elegans (more impressed than I am by this demo).
The 2024 nature paper this is based on isn’t particularly misleading/exaggerated and this demo doesn’t represent significant advancement on this paper. I would recommend reading the paper (or asking an AI questions about this paper etc) to people interested in how impressive this demo is.
The claim “I think the fruit fly upload situation is one of those things that’s like this comic” doesn’t seem that accurate to me given the communications mentioned above. This would be true if we were just talking about the 2024 nature paper and the EON blog post, but we aren’t. There are caveats in the original communication that aren’t being picked up by third parties, but this isn’t the only important thing going on.
More speculative and involves psychologizing (generally a risky thing to do). Based in part on private info and talking with Michael Andregg once:
I do think that EON / Michael are likely pitching this reasonably hard, in somewhat misleading ways, to various groups.
I’d guess that Michael’s epistemics about what’s going on and how close we are to various targets aren’t great and this probably applies to EON as a whole to some extent. I do find EON’s blog post reassuring with respect to EON’s epistemics.
It’s common for startups to do behavior like this and have bad epistemics in this sort of way. My understanding is that this doesn’t typically significantly undermine the ability of startups to achieve their goals. Thus, it’s not clear that having not-great epistemics—insofar as my speculation about their epistemics is true—would make EON that much less effective at achieving their goals (and it’s worth noting that their apparent epistemics are probably better than that of a typical start up). That said, it might result in third parties being systematically misled about how close EON is to achieving their goals. If I was considering working at or investing in EON, then I would certainly take this into account when deciding how promising/tractable current work in brain emulation is, but conditioning on views about tractability/promisingness of the field, I would likely consider EON to be a pretty reasonable bet within that field.
I frankly think calling the Eon video any sort of “upload” is quite misleading and exaggerated. There are at least two fundamental reasons for this:
@Aurelia, as you, Ken, and even Eon (later on in their blog post) correctly point out, this was a leaky integrate-and-fire (LIF) model built from the fly connectome. So it’s not even close to the full brain of the fruit fly: no neurotransmitters, no synaptic weights, no synaptic dynamics from the fruit fly. We are not even faithfully simulating its brain in silico.
Not only is the central nervous system not a true upload, but the motor system isn’t either. What is instead used as a mapping between this LIF model and motor outputs is a policy that is hard-coded (not even imitation-learned via RL, though later on they & others do this) from fly behaviors from the NeuroMechFly team at EPFL. So the LIF model they use is neither necessary nor sufficient for the generated behavior: the fly policy can walk on its own without any additional inputs, as the EPFL team already demonstrated.
Thank you for trying to explain this!
Does that mean that the brain itself was simulated, using only info from the brain scan, while other techniques were used for simulating the body and environment?
Was it a specific fruit fly, or a simulation created using data from multiple fruit flies?
Now that I see this tweet from Ken Hayworth, it looks like you’re probably right about the fly upload.
(I chatted with Aurelia some weeks ago and was overall pretty impressed, but she also made a claim like this about the fruit fly and I was somewhat skeptical / worried that the claim was overstated.)
Does Aurelia’s elaboration assuage your concerns?
Not that much. I don’t understand what the actual experiment is, and in particular how much it is showing that we got algorithms (even opaquely) out of a fruit fly connectome. In any case, IIUC by all descriptions, it doesn’t really hit at the challenge of simulating neurons well enough that the simulated brain could learn anything. That’s what I expect to be difficult and to be needed for really useful simulations. (Separately I think brain emulation is dangerous; see https://www.lesswrong.com/posts/jTiSWHKAtnyA723LE/overview-of-strong-human-intelligence-amplification-methods#Problems )
Oh boy! I’ve been waiting for this to become commercially available since I first heard the possibility discussed in Eric Drexler’s apartment in 1980! Sign me up!
Well, on second thought, sign me up after a few other people have signed up, and the organization has some proven longevity. I’m signed up for cryopreservation, even though I think it has only a 5% chance of working. I’m not going to drop that, because it protects me if I die unexpectedly. But presumably I could avail myself of Nectome’s services if I had a slow illness. I’d need enough time to sign up with Nectome, cancel my existing coverage, move to Vermont, convince two doctors of my seriousness, wait 15 days, and lightly kill myself.
It’s funny—when I first heard of this possibility, 45 years ago, gluteraldehyde was the cross-linking preservative that was mentioned. And it’s the one Nectome actually uses. Has chemistry not moved on in 45 years?
(Right now we’re only in Oregon but Vermont is top three for future expansion)
I love Engines of Creation! But somehow, I managed to invent ASC first and THEN I read about it in Drexler’s book. Might have saved me some time had I read about it earlier (though he’s missing the critical blood brain barrier permeabilization step so as written in that book it doesn’t work)!
What makes sense to do now?
If you want to prepare a bit now, I would keep your insurance and your cryonics membership and add a rider that makes your insurance pay out early if you’re diagnosed terminally ill. I can get you the language if you want, I have it on my insurance policy. Then you buy the preservation if and when you need it.
In the meantime, you might be interested in our pre-sales. They’re transferrable and as cheap as they’ll ever be.
The MAiD aspect of preservation might seem intimidating at first, but we’re committed to working with our clients to make it a smooth and positive experience. Our clients won’t be on their own when trying to navigate the logistics.
Why haven’t we found something better than glutaraldehyde?
You know it’s really funny: Here’s a quote from Hayat’s amazing book “Fixation for Electron Microscopy”, published in 1981:
> I appreciate that present-day methodology moves faster than any printing press and that the useful half-life of any tome dealing with preparatory methods may be depressingly brief.
45 years later, I STILL consider the Hayat book to be relevant and we’re still using approximately the same techniques. Hayat lived at a time that saw improvements to tissue preparation technology every few months, so much so that it seemed like his book would be out-of-date the moment it was published. So what gives?
Why do I think we’re still using glutaraldehyde? Basically I think we just found one of the most optimal preservation molecules early on, and it’s really hard to improve on it. Glutaraldehyde passes through membranes like they aren’t there and doesn’t cause osmotic effects, it reacts with proteins in seconds, it produces gels that are really tough both chemically and mechanically. In terms of (# of aldehyde groups / molecular weight) it’s hard to beat with two aldehydes, five total carbon atoms, and a MW of ~100. People have tried different carbon chain lengths and the alternatives are all basically the same.
The other factor here is that the search space for improving electron microscopy results is mostly flat. I’ve tried hundreds of little tweaks with carrier solutions, glutaraldehyde concentration, various additives, all kinds of stuff. The things that really matters is total ischemic time, and the osmolarity of the carrier solution. 1% glutaraldehyde vs 4% glutaraldehyde? No visible difference on the resulting electron micrographs. Cacodylate instead of phosphate buffer? No difference. Formaldehyde instead of glutaraldehyde? Basically no difference. 16 minutes vs 12 minutes ischemic time? Half the brain won’t perfuse at 16 minutes, but at 12 minutes it perfuses fine and the images look good (though with hallmarks of ischemic stress that don’t interfere with connectomic traceability).
I’d love to read the language of the life insurance rider. That sounds very helpful (versus trying to figure it out on my own).
Feel free to drop us a line at hello@nectome and I’ll make sure that gets to you.
Why only whole-body?
I have a couple thoughts on this!
1) In general I’m very conservative about preserving things and wouldn’t want to throw the body away without a really compelling argument for why it’s going to be fine for the person being preserved. I don’t currently have that argument.
2) Now you could certainly argue that with just a brain it’s possible to fully reconstruct someone. I think that’s probably true because the task of reconstructing a body ultimately is about satisfying the expectations of the person’s mind and enabling all their capabilities, and you should be able to “read off” what the brain was expecting from the models of the body contained in the brain. Especially if it’s an interactive process with the person actively participating and saying what feels more or less right. I think it’s probably true that you can reconstruct a person from just a brain with no losses that we’d deem clinically relevant today. But I don’t believe that at 95% confidence so I don’t want to, in my ignorance, throw away something that ended up really mattering.
2.5) Note this line of reasoning applies to the brain itself! Do you really need to conserve the brainstem? How about the cerebellum? Optic nerve? In principal it’s probably possible to infer these structures. I estimate it’s more than 50% likely that this can be done with future technology. But in my ignorance and humility I say that we should just preserve as much as we can and let the future sort it out.
3) Spinal cord has a lot going on! Take a look at grey matter in the spinal cord. This is from the anterior horn of the spinal cord and the image is from https://synapseweb.clm.utexas.edu/atlas/1-neuron/13-perikaryon/1304 :
I didn’t appreciate starting out how complicated the spinal cord is, it’s got grey matter, white matter, synapses, it’s part of the central nervous system after all. But starting out I thought it was more of a bunch of cables and not that interesting. When I actually looked at the structure I became much less comfortable throwing it away.
4) I also like to consider the experience of someone being revived. Suppose it is possible to reconstruct from a brain only but it requires an active search process with the person participating. That might feel like years of physical therapy from that person’s perspective. And they might have dysphoria while they’re trying to make their body feel right. If I can spare my clients that inconvenience by retaining their bodies I’d love to do that.
5) Because we’re storing at −32°C the relative cost of head-only vs whole body is minor compared to traditional cryonics. It’s just not as much of a concern compared to conserving precious space in a dewar.
I was somewhat skeptical of the importance of the spinal cord for general cognition, but I did find a few articles that have me reconsider and become somewhat agnostic:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9165403/
>The impact of the anatomic level of injury in the spinal cord on cognitive function has also been investigated. In a study carried out by Wecht et al. (2018), it was shown that patients with SCI at or above the T1 level have a lower performance on cognitive tasks (Wecht et al., 2018). On the other hand, given the fundamental role of the spinal cord in the functions of the autonomic nervous system, it has been suggested that hemodynamic events after SCI (chronic hypotension and orthostatic hypotension), particularly in individuals with high spinal cord lesions (i.e., above T6), may contribute to the development of distinct patterns of cognitive impairment (Chiaravalloti et al., 2020a). In line with these findings, Chiaravalloti et al. (2020a, b) also identified a relationship between some cognitive functions and hemodynamic changes, concluding that, an increase in cerebral vascular resistance leads to the worsened performance of the individual in tasks that involve cognitive activity.
It’s far from cut and dry. After all, serious spinal cord injuries can ruin QOL, and are usually due to some form of trauma. But I do find this to be surprising and suggestive.
IMO, it is worth it from a pure PR perspective. Chopping heads off gives people the ick.
It definitely goes over well with normies. Plus, since aldehyde preservation is stable at room temperature, it opens up the possibility of a completely standard open-casket funeral, which is really nice for people whose families aren’t necessarily sold on the whole preservation thing.
I would’ve expected the MAiD to be a serious PR issue.
Ten years ago, it was. There’s obviously still some people who aren’t comfortable with it, but I’ve been surprised how rarely people register any kind of discomfort; they’re way more likely to express concern about, say, overpopulation, or whether the future would want them.
Nectome definitely goes over well with normies? I’m somewhat surprised. I’d expect most people would think it’s weird/creepy/cheating death (derogatory), even if you don’t chop off your customer’s heads.
It was absolutely a huge surprise. Obviously not everyone is into it, but I’d say that the median reaction I get when I chat with random people is closer to “huh, I didn’t realize the science was that good yet” than “how dare you defy the natural order.”
People who’ve been in the business longer than I have tell me that this is a big change over the last ten years. I think those of us who’ve been into preservation for a long time may have some cached views on the popular attitude which aren’t as accurate as they used to be.
I’m going to be in the comments section too, so I wanted to introduce myself briefly—I’m Charlie, I’m Nectome’s chief of ops. I’m really excited to be sharing this with the community!
For the purpose of resolving all doubt, confirmed.
This sounds really cool!
Do you know how it would work if someone not living in America wanted to use your services?
This works for people outside the US! Oregon allows anyone physically in the state to make use of its end of life laws (one of only two states that does so, the others have residency requirements that are likely unconstitutional according to the Oregon Supreme Court). So as long as you’re terminal and can get to Oregon we can preserve you.
What kind of visa do you need for this? Do plans to use MAiD counts as plans to leave the country?
What does the future have to look like for high confidence that your business will still be around in 20 years? 50 years? 100 years?
I have been signed with Alcor for almost 20 years. What is the case to switch, irrespective of the science and process (those matter, but what is the business survivorship case)?
I think Nectome’s business case is very strong and that preservation is going to become a new global tradition soon. I think within the next decade we’re going to see very impressive uploading results which will validate that our preservation method works (whether you want to be uploaded or not, compelling uploads that start with aldehyde fixation show that the information was successfully preserved). At that point I think 0.1% − 1% of people will seriously consider preservation, and Nectome will be very successful.
In the case where it takes a long time for preservation to become popular, Nectome will also be fine: we’re already making pre-sales and have a plan that works for a variety of demands.
That being said, I also think there’s a lot of scenarios where Nectome goes out of business, but the people who’ve been preserved are still maintained:
Nectome goes out of business, preservation becomes popular: If preservation becomes a new global tradition, then there will be whole political classes that vote based on the treatment of preserved people, because people they love are preserved people. I hope that one day we’ll have a separate legal category for preserved people that respects the profound loss of future potential it would be if they were destroyed, and instead treats them like we treat people in a medically-induced coma today. And in that case, Nectome would be subject to strict regulations concerning long-term care. If Nectome went out of business, it would be like a hospital going out of business that had several patients in medically-induced comas. It would be legally required to move preserved people without disruption of care. I think this future is actually very likely, despite the low numbers of signups for traditional cryonics over the years, because I expect compelling results in uploading in the next decade to dramatically increase people’s willingness to consider preservation.
Nectome goes out of business, preservation remains unpopular: I think Alcor got it right when they designed their system for long-term care of people. They use a separate company to actually hold preserved people, so that if Alcor (the entity doing perservations) goes out of business, Alcor (the separate entity holding preserved people) continues its operations. Startups fail all the time because they take risks and are doing new things. But graveyards fail much less often, because they get initial endowments and have very predictable costs and few people to pay. So Nectome has two components, one that works more like a startup and one that works more like a graveyard, and it’s less likely for the graveyard-like part to go out of business even if the startup-like one fails. (Note that while I’m using graveyard as an analogy we don’t consider Nectome to be in any sense an actual graveyard.)
All parts of Nectome fail, what happens?: Ultimately we have a big advantage in that long-term care of people preserved with Nectome’s methods is fairly easy. We store people at −32°C which is readily available commercially. Preserved people are stable at room temperature for some amount of time, I’m quite sure it’s longer than a month based on our own accelerated aging experiments so far, but I think in reality it’s probably years or even decades. Preserved people each come with an endowment that covers long-term storage, so in the event that all parts of Nectome failed I think that many companies offering cold storage would be interested in taking up a storage contract because it would be profitable for them.
No money AND no Nectome: Say there’s a war or some major upheaval and both Nectome and most / all of the money is lost. In that case, as Nectome’s last corporate act, we’d move people to permafrost storage who wanted preservation at all costs and were willing to lose chain of custody over it, and cremate the rest.
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What about your Alcor membership? Keep it! We don’t do memberships at Nectome, instead people just buy preservations when they need them, or in advance. Two considerations on this:
I’d add a rider to your life insurance policy that enables you to get paid the full amount of the policy if you become terminally ill. I can get you the exact language if you want, I’ve got it on my life insurance. Insurance companies don’t charge much for this and it’s immensely helpful for doing preservations. If you do this and keep your Alcor membership, then if you die suddenly Alcor gets you. If you have the ability to plan ahead you can use Nectome.
You might consider buying a preservation pre-sale before we open. They’re transferrable and we’re selling them at a substantial discount. Details here.
What’s the structure, finance, and governance for the graveyard-like part of Nectome?
non-profit? perpetual board?
what fraction of the cost is put into a trust for long-term preservation?
It’s not set up yet but we are broadly going to model it after Alcor’s long-term patient care fund. Non profit. They survived for decades; no sense in changing something that isn’t broken.
Will you have much savings early on?
I’m a little confused by what you mean by ‘savings’?
Are you talking about the amount we set aside for each person, the total amount in the endowment dedicated to long-term care, whether that amount changes over time, something else? Looking forward to getting you a complete answer!
The total amount in the endowment, and plans about its changes over the next several years, please.
Gotcha!
There’s no endowment currently because we haven’t preserved anyone yet.
With each preservation, we’ll set aside enough money to cover 100 years of storage at the time of preservation and those funds will be invested in something like index funds. I don’t think that we will actually need 100 years of storage, but a 1% drawdown should be conservative and long-term sustainable, especially since we expect advancements in refrigeration technology, the preservation technology itself, and energy production (like fusion power) to reduce the cost of preservation maintenance over time.
Our constraint regarding the endowment is that it needs to be true that the whole arrangement with the endowment is appealing enough that another company would be interested in assuming responsibility for continued care of preserved people because it would be profitable, in the case where for some reason we had to hand off long-term care to another entity.
The preservation endowment will grow with each preservation and be highly dependent on sales, but I think we will be getting to thousands of preservations per year in a few years and that will translate to > $10 M in the endowment in total at that time.
Some people voted this down with disagreement but didn’t voice the disagreement. I am curious about which part they are disagreeing with. Is it that they see the story as implausible, or imagine a case that isn’t covered, or something else?
So I guess the process would be like, you’re ready to use Nectome with MAiD, so you take out your life insurance policy, pay Nectome, and then use MAiD, all in a short timeframe, otherwise there’s a period where you don’t have an insurance policy for Alcor, and could die without MAiD. Sounds risky. Alternatively, have 2 full insurance policies, but that increases the cost significantly.
We want people to be preserved and we’ll work things out to make sure people don’t have weird gaps in coverage like what you’re describing. As part of getting set up with us you can name a specific emergency services provider in the event you can’t be preserved by us, and we’d forward the payment if that came up.
In practice it would be pretty rare for someone to die right before they went through with MAiD, but it’s good to plan ahead.
Specifically, if someone had an Alcor membership, paid us to preserve them, then died a day before we were going to preserve them but after they had paid us, and had specified beforehand that they wanted Alcor to preserve them in that case, then we would call Alcor ourselves and get the person preserved emergency-style (and we’d be in communication beforehand in any event so everyone was on the same page).
You can probably take out a loan to pay Nectome and MAiD, then pay back the loan with life insurance a couple of weeks later once you’re already preserved.
Do you get life insurance on MAiD? I’d be very surprised.
edit: well, the google AI agent says yes you actually do! Color me impressed. Guess they trust the legal checks on that.
Most life insurance policies have a 1-3 year exclusion time where if you commit suicide during that time they don’t pay out. But if it’s a long-standing life insurance policy, past that exclusion window, it does pay out even in the case of suicide, with very few exceptions.
MAiD is special because you count as having died of whatever your underlying disease is. It’s not legally suicide. Your death certificate says you died of cancer or whatever your terminal illness was, and Oregon’s gone to some lengths to make a clear distinction between MAiD and suicide. In fact, Oregon law actually specifically prohibits insurance companies from penalizing you as if you’d committed suicide if you make use of MAiD. So in principle even if you did MAiD within the suicide exemption window of a typical life insurance contract, it would still have to pay out. In practice I don’t know of any case law where it’s actually come up. But check out ORS 127.875 §3.13. Insurance or annuity policies, which says:
Thanks for the answer. I’ll read your research and think about whether it makes sense.
Hi! Thank you so much for your work. I have been wanting to ask some questions ever since I read your Asterisk article!
Given that we actually can restore vitrified brain tissue back to life right now (mouse brain hippocampus slices, ~70% functionality, synapse plasticity restored; much less consistently whole brains), does this mean Alcor and CI’s vitrification-only approaches are not so hopeless?
Doesn’t glutaraldehyde permanently damage some of the chemistry of the cell? If engrams are an important part of information storage in the brain, and engrams are encoded chemically, and thus the connectome isn’t the whole picture, doesn’t this mean that fixation by that method could destroy important information?
Why aren’t Alcor and CI doing MAiD? If you are right about the 12 minute window, and they believe you, wouldn’t they want to set up their own clinics in Oregon for this, and to offer preparatory services as well? Have you reached out to them? Have they responded?
What do you think the prices will be in 5, 10 years? Will this always cost as much as a house?
What are the strongest arguments in favor of this method not working?
(Aurelia is really excited about this question and wants to sit down and give it a thoughtful answer, so it’s been waiting on her having a solid block of time to respond.)
How much it cost?
How much damage if the body temporary returned to room temperature?
What do you think about other methods of chemical preservation which do not require cryogenics?
It’s going to be $250,000 at launch, but we’re offering limited pre-sales for $100,000, or a $20,000 discount card that upgrades to a full preservation if you wait 10 years after purchase. (The latter is intended as an option for healthy young people who plan ahead.) Details on our substack.
No damage from brief excursions to room temperature, where brief is measured on the scale of weeks.
I’ll leave this one to @Aurelia, who I think will have fun answering it.
Other methods of chemical preservation:
The ones I know of are the body-world’s-style wax infiltration technique, resin embedding as is used for electron microscopy, and various kinds of fluid preservation mostly involving alcohols but sometimes involving spicy things like mercury compounds, etc. A really good book on this stuff is Fluid Preservation, a comprehensive reference, though physical copies are hard to come by.
The body worlds version is a non-starter because it doesn’t preserve nanostructure. It prioritizes color and visible structure, but if you looked at that tissue under an electron microscope there would be a lot of damage. (the reason it causes damage is gas bubbles + a bunch of other stuff. Also the last time that I checked on this method was 12 years ago, I’m only 75% certain I remember this part correctly.)
Resin embedding does preserve nanostructure. It doesn’t preserve lipids nearly as well as glutaraldehyde (because lipids are more soluble in the resin than in water), but you can partially stabilize the lipids by crosslinking them with osmium tetroxide or other related compounds. But unfortunately, no one knows how to infiltrate osmium tetroxide or resins into tissue if the tissue is large. I spent a year trying to get osmium tetroxide and resin perfusion to work, and got some impressive results, but never managed to get a whole mouse brain to fully embed; there’s always small mm-sized regions that get washed out. It’s a very annoying problem. Recently the ODeCO protocol and other similar protocols look like they might be able to get a whole mouse brain. Maybe. But these methods all use immersion and diffusion and sometimes weeks to complete (check out the methods section of the ODeCO preprint, it’s fascinating). If it takes more than a week to process a mouse brain that’s 0.35 ml of total volume, it will take much longer than a year to process a human brain that’s ~1,200 ml.
Alcohol preservation is done with diffusion so it would need initial fixation to preserve nanostructure. And alcohol will disrupt lipids more than cryoprotectant will as I understand it. But I think alcohol preservation is pretty underrated and worth exploring—there’s some very beautiful specimens that have lasted for hundreds of years at the Royal Society, for instance.
I see no pushback about the actual science of it in the comments, which seems surprising. It’s great that there is a new brain preservation company around, but I think the results are somewhat over-claimed. I’m not an expert in biochemistry, but if I understand correctly, your (new) preprint is basically: take n=5 pigs, try to have their brains preserved, which fails in the first two of them because of incorrectly placed cannula, then succeeds in the next three, in particular the last one with t=14 mins gap. Then look at the damage on a few sites under microscope and judge them to be OK. For reference, the abstract says that you develop “connectomically traceable whole brains [...] and establish that 14 min is the approximate length of the perfusability window”. The new preprint is not peer-reviewed, and the old paper is from more than 10 years ago. (I see that it’s actually has 61 citations in google scholar, it would be useful to know what was the progress / assessment from the scientific community since then.)
Tiny sample size, imperfect experimental setup, no published actual quantitative data, as well as obvious conflict of interest on top of this makes it hard for me to fully believe in the results. FWIW I asked one biochem PhD friend of mine for opinion, and then also ChatGPT, both seem to strongly agree that this is a cool proof of concept, but significantly over-claimed as far as scientific evidence goes.
Do you have any plans to offer a “planned emergency response” method, where people who expect to die soon but do not want to kill themselves can pay a team to be stationed nearby until they have their heart attack/stoke/whatever?
Unfortunately the pre-mortem ischemia continues to be a real problem. I’d expect essentially all people preserved under those circumstances to suffer profound brain damage before a doctor was ready to declare death.
You also run into the additional problem that the twelve minute window is just very unforgiving. You can’t have a team nearby in an airbnb waiting for a call; you’d need multiple surgical teams taking shifts literally at the client’s bedside, for days or weeks.
Overall, I don’t think this is something that’s going to be practically compatible with the kind of quality standards we want to hold ourselves to. That being said, of course we have ambitions for continued research into how we can extend the technology to catch more people, and quick respiratory deaths like heart attacks are going to be the strongest candidates for that.
This is exciting. I’ve created a Manifold market on whether this method works:
Oh, thanks so much for doing that—we spent a bunch of time yesterday debating how to word a market such that people wouldn’t worry about whether we’d evaluate it fairly, but of course someone else running it is just better.
This is fantastic news, thank you for posting this! I have several questions detailed below, some of which probably will be answered by reading the materials you linked, but figure I’d ask anyway:
1) Does this solution apply to all neuronal tissue (spinal cord, distal motor neurons), or just brain? If it hasn’t been evaluated yet, would you expect it to?
2) What does storage look like in terms of location? What is Nectome’s strategy to pay for storage in ~perpetuity/plan for right-tail events (ex. an energy price shock of 10x+ due to AI datacenter buildout that lasts for several years, or major natural disaster at storage location)?
3) As (I’m assuming) the lead of Nectome, are there any major efficiencies or economies-of-scale that you can foresee several years out? How do you imagine the 100,000th preservation compared to the 1st in terms of price, cost, etc?
4) The cumulative discount card says “Purchase a full preservation pre-sale with this discount schedule based on the market price (initially $250k) at any time”—if the market price changes, are the discount percentages held constant?
Thanks again!
I hope you become huge
You’ve started the team singing Giant Woman around the office all day.
How do you see yourself fitting into the existing cryonics ecosystem. Ultimately a competitor to Alcor, Cryonics Institute, etc.? Provider of services to them?
I ask because I and many other people already have arrangements with existing orgs, and if there’s better tech we likely want to switch to that, but financially switching providers seems likely to be non-trivial.
We will do only high quality, regulated, scheduled preservations and don’t offer emergency services. I think people who have existing emergency arrangements should keep them and use them if they need emergency services. We’re not competitive in that sense.
I do think it makes sense to put a rider on your insurance policy so you can access the money earlier and pay for a planned preservation, and if you happen to need emergency services to instead use that money for emergency services.
In the long run I hope that the entire tradition of end-of-life care will change and people will consider scheduled preservation to be a critical part of end-of-life planning. Eventually I hope that emergency preservation that can meet our high quality standards is invented and deployed in every ambulance and hospital in the world, by popular demand. To get there, we’re offering what we can right now that will meet our quality standards, and that means pre-scheduled.
Fair enough. I’ll be honest, though, sorting out all the details seems complicated, especially when I already am set up for one thing (Alcor) that’s much better than nothing. Given I expect many of your best potential customers are in the same situation, finding a simple solution that integrates with existing cryonics providers is likely a strong way to grow your customer base, and I hope you pursue it.
I think it’s entirely possible that more streamlined paths for transition will end up being built as the company matures. In the meantime, I think some of the details may actually be easier than you’re imagining (e.g. the insurance rider is a lot simpler than it sounds), and we’re certainly happy to walk people through the process as necessary.
There’s got to be some way to see how much info we can reconstruct from brains which were cryopreserved a few hours after death. Perhaps if we could grow brains in a vat, we could make two copies of the same brain, and cryopreserve one brain properly and let another degrade before cryopreserving it. Then the former copy serves as a ground truth for reconstruction attempts. Of course, that’s replacing one hard problem with another hard problem. But it seems worth spending more than literally 5 minutes on this problem.
One experiment I’d LOVE to see (which I haven’t done yet because I’ve been working on the fixation stuff but might in the future) is to take YPF mice (sparse fluorescent labeling of entire neurons) and freeze / cryoprotect them in various combinations with various post-mortem delays, then do expansion microscopy and 3D imaging to see what happens to the YFP pattern. The idea is that you’d have the ground truth of what the intact neuron was and could see if it’s still traceable after the preservation attempt. I would be very impressed and ultimately convinced that a protocol maintains traceability if you could trace images with the YFP signal stripped and then have that tracing result match the YFP ground truth.
Certainly there’s some issues actually doing the experiments technically (which is one of the reasons I haven’t done them yet). It’s harder to do well than it might seem. But I do think it can be done, and I also think it’s never been easier because of expansion microscopy making it much easier and cheaper than it used to be by a factor of 100-1,000x.
growing brains in a vat would not produce identical brains, not even vaguely close. It would produce more similarity than between most brains, certainly. also, like, being a brain in a vat probably sucks big time
Sure, but I was assuming some sort of magical growth process which could make identical brains, perhaps some form of nanotech. I realize that’s a ridiculous ask and doesn’t reduce the difficulty of the problem in any way. Heck, it increases it. But that’s the only thing I could think of that would definitely produce identical (upto connectome) copies of brains with less than 5 minutes of thought.
Amazing to see this new option enter the space. Fantastic work; I’m a fan!
Excellent to see this up and you publishing more about what Nectome is doing!
How much warning would you need to get a team together to do this, for the case of someone being taken off a ventilator or other kinds of life support? Most US states don’t allow MAID, but my mom suffered from a bad pneumonia infection and probably could have survived another few weeks if she hadn’t declined a ventilator, and presumably if she had been put on a ventilator she could have precisely scheduled her “death” by turning it off. Could she have been a candidate for your services? And would she have had to travel to Oregon while still alive to get them?
Incidentally, my wife and her brother both died of heart attacks that happened while they were in a hospital for other reasons.
Congrats on the launch and on getting your pig results published!
Thanks so much! LMK if you have any questions or thoughts about the post. Or if you want to offer an argument for standards below “traceable connectome”. I know we’ve had a longstanding difference of opinion on that and I’d be delighted to chat about it here if you want!
Sure! First, to be clear, I fully agree with you that legal death via MAID followed by perfusion fixation offers (clearly) the best preservation quality available today.
I think of the BPF traceability criteria by contemporary volume EM as more of a rule-in than rule-out standard for preservation quality. Just because it’s not possible to trace all of the processes today doesn’t mean that a sufficient amount of information isn’t still present in the preserved brain that would allow connectivity to still be traced by future inference techniques. Briefly, this is because I think that it is very likely that in the future we will be able to use combinations of biomolecules that are (combinatorially) unique to each cell/cell process to solve ambiguities caused by discontinuities in cell process tracing. See: https://brainpreservation.github.io/Inference
I suspect that we probably agree on most things, so let’s try to find something we disagree about!
I think we probably agree about the following (let me know if I’m wrong about any of these):
Damage that seems like it should destroy information often doesn’t. Our intuitions are often wrong on what can be inferred, and the bias is normally in the direction of more information being lost than is actually lost. We tend to think something’s “a mess” when it can actually be fully reconstructed.
Even with a frozen brain, you can’t prove that any information relevant to restoring a person is truly lost. Straight freezing crushes and disrupts brain tissue, but maybe there’s enough biomolecular information to reconstruct everything. I personally wouldn’t be that surprised if this was the case.
There’s some physical change in the vasculature of brains that happens post-mortem and causes difficulty in re-perfusion, and that change happens at approximately the 7-15 minute mark depending on how you measure it. Brains that sit with blood inside them, but no blood flow, for longer than this window, will not re-perfuse uniformly with blood, washout solution, or fixative, but instead there will be sections of brain that fail to perfuse.
Brains can become severely damaged and even outright necrotic in some areas pre-mortem, before the person’s heart stops and legal death could be declared. The amount of brain damage present at death depends on how the person dies, but it’s relatively common for people to experience terminal comas lasting hours to days before death.
We (humanity) know enough neuroscience today to say that some aspects of a person don’t need to be preserved. Dynamic electrical activity is one such thing that can say with confidence doesn’t need to be preserved, because otherwise it would contradict our clinical experience with DHCA.
As we learn more neuroscience, we would be able to definitively say that more things don’t need to be preserved. For example, we might be able to show that certain brain regions share so much mutual information with other regions that only one needs to be preserved, with “doesn’t need to be preserved” meaning that a person could be preserved, the thing discarded, and the person restored with no or minimal clinically relevant problems. We might learn enough neuroscience to say that inhibitory synapses don’t need to be preserved, because ultimately they are implementing non-memory-relevant network regulatory tasks. We might be able to say that the spinal cord or brainstem or hippocampus doesn’t need to be preserved, because they’re all inferable from cortex.
Now here’s where I think we differ, and it’s on what the standards for our standards should be!
What should the bar for “acceptable preservation” be today, given our current neuroscience knowledge?
I think we know enough neuroscience today to say that preservation does work as long as almost all biomolecules are preserved and the brain remains traceable after preservation, and “works according to current neuroscience” should be our minimal bar for “acceptable preservation”.
This standard demands a lot from today’s preservationists, but it’s demonstratively achievable given the work I’ve done in pigs / human cadavers over the last several years. And so we as preservationists should hold ourselves to this standard, out of humility and a desire to offer the future something they can use. If we want to lower that standard we can, but a lower standard needs to come with additional neuroscience knowledge so that we can confidently say that a lowered standard does work according to current neuroscience in spite of not preserving as much.
I think that if we always hold our “acceptable preservation standard” to be demonstrably preserving enough information that neuroscience says it works, then that both gives us the best chance to deliver to the future something they can actually use, and gives us the best shot at becoming a standard, evidence-based part of end of life care.
The “standard for our standards” should be “works according to current neuroscience knowledge.”
I want preservationists of this era to be able to be sued for malpractice because their technique was sloppy and they didn’t deliver preservative chemicals to a dime-sized brain region within 15 minutes post-mortem.
I want straight freezing, traditional cryonics, or any other method to be accepted as good techniques, if and only if they come with enough new neuroscience knowledge so that we know they’re preserving enough information that they work.
Now, I suspect you would want to argue for a different “preservation standard standard” that’s not “works according to current neuroscience”, I’d love to hear your thoughts!
Thank you so much for explaining where you think we agree and disagree. I totally agree that finding disagreements is more interesting, even though we overall seem to agree on this topic more than the vast majority of people in the world.
I agree with all of your bullet points with the partial except of the 7-15 minute perfusion one. I don’t think there’s necessarily a physical change that occurs in the vasculature within that time window that absolutely prevents subsequent perfusion. To me it seems more complicated on both the higher and lower ends of the range. For example, my understanding is that animals have been revived after global cerebral ischemia for up to 30 minutes. I think it depends on the perfusion system used and there also seems to be a significant amount of currently unexplained biological variability. But this is a topic I’d like to learn more about and I don’t pretend to totally understand it, so I’m curious to hear more of your reasoning.
Regarding standards for brain preservation, I find the discussion very important but not yet settled. To use an analogy from clinical medicine, we are discussing the use of surrogate endpoints to predict whether or not someone can be revived in the future when technology has improved. Unfortunately, we don’t have any well validated endpoints for this outcome. Ken has proposed the criteria of connectome tracing by contemporary volume EM. However, this completely ignores the possibility of future molecular mapping to infer the original states in the case of morphological alterations. If this is possible, which I think it is, it changes everything. So I think we first have to determine more rigorously what the surrogate endpoints are that indicate information theoretic death. Basically, while I agree with you that one or multiple surrogate endpoints are urgently needed in the field, I just don’t agree with the current ones that have been proposed so far. So I think there is more basic science research needed to determine that, specifically regarding (a) how different types of structural information such as molecules and morphology correlate with one another in the preserved brain and (b) what types of structural information can be used to infer cognitive information (such as research related to the Aspirational Neuroscience Prize). More on this here: https://brainpreservation.github.io/Assessment#volume-electron-microscopy
I like that Nectome uses this approach and those standards; I think it’s a very valuable organization to have as part of the brain preservation ecosystem.
I think exploring some form of standards, or at least some options for third party quality reviews would be very valuable.
I imagine you’re not making the following strong claims, but I can’t tell for sure, so would like to check.
You’re not saying “It should be illegal for someone to get their brain preserved if it takes more than 15 minutes to start the procedure because the medical intervention wouldn’t be good enough so they should be forced to completely die instead and not attempt to preserve them.”, right? I would strongly disagree if that’s what you were saying.
You’re not saying “It should be illegal for someone to prioritize other preservation metrics over methods that allow for easier microscopy verification of structural preservation even if that’s what they prefer”, right? I would also disagree with that, both because I want people to be able to do whatever they want, and also because there’s still enough uncertainty that I don’t think we can be sufficiently confident about some alternative approaches not being actually meaningfully superior in some ways. (I do assign more probability mass to prioritizing structural preservation, and that influences my decision making for myself, but also I’m not aware of research proving that cryonics without fixative does not preserved important structure, and forcing people to not use that seems at the very least premature.)
Absolutely not saying either of those things. If nothing else, I don’t think the government has any business telling people what they can do with their own brains, or what kind of medical procedures they can hire someone to perform on them.
We’ll get into more detail in future posts about what kind of mechanisms for accountability we are excited about. Broadly speaking, though, we’re interested in labeling and certification, not in any kind of prohibition on alternative services. The hope is fundamentally that ordinary laypeople will be able to easily understand the stance of the scientific community at large and what procedures meet a reasonable standard of care.
wonderful!
nice title; it’s also the title of my blog 😛 https://lessdead.com/
Nice blog! The split-brain preservation April Fool’s post was really funny.
Similar to what Alcor has done, will you create patient/case reports once you start having your first patients, and make them public? I think it’s great news to have a new player in the cryonics space, and the relative lack of friction is very nice, now just comes the long haul of establishing trust.
Short answer: we’re going to do something that IMO is even better—third party verification on a per-client basis.
Longer answer: Cryonics is in a difficult place as a medical technique because it suffers from the “no feedback” problem, as Mike Darwin has spoken about for many years. If I am a foot doctor and I hurt people’s feet, then they can sue me and eventually I’ll go out of business. But if I’m a preservationist, it can be very hard to tell whether a preservation actually worked or not, and the ultimate personal experience of the person being preserved may be decades away.
Lots of more normal medical practices have quick feedback to they’re able to achieve good results, and consistently deliver those results over years. But preservation doesn’t naturally have that. So in order for preservation to be rigorous, we have to build a system of feedback ourselves, and ideally make it even more rigorous than most medical techniques to compensate for the fact that we don’t have the client’s personal experience of the procedure.
We’re going to rely on the Brain Preservation Foundation to help keep us honest. Every client’s preservation will be reviewed for quality, and we’ll post our success rate so that people know how likely they are to be preserved successfully. We hope eventually other cryonics organizations will join us and we will have a “preservation leaderboard”. If you want to know more about the kinds of things we’ll be reporting for each client, check out the BPF’s Accreditation Page.
We’ll be talking about this in more detail in an upcoming post as well. It’s really important!
Is it possible to get a body preserved by Nectome, and then stored by Alcor? (I don’t know if this is a good idea, but I’m trying to understand the options)
Right now, as I understand it, storage at Alcor would be at liquid nitrogen temperatures (-196°C), which is too cold to be compatible with our protocol. If you try to store one of our preserved persons at that temperature, they will shatter, which is unacceptable according to our quality standards. (To be clear, −196°C also shatters people preserved with Alcor’s methods.)
The target temperature needs to be either −32°C and higher (to prevent freezing), OR somewhere around −122°C with good control of temperature excursions (to precent devitrification or shattering). Intermediate temperatures are not good, for example, it’s actually worse for our preserved people to be cooled down to −90°C for a day then it is for them to be warmed up to 50°C for a day.
Note that the cost to store at −122°C is substantially higher than the cost to store at −32°C. The rough price ratio annoyingly depends a lot on economies of scale, due to the square cube law, but it’s around a factor of 10 or so for realistic small- to medium-scale preservation scenarios. So we definitely prefer −32°C all else being equal: it’s a lot cheaper and it doesn’t cause problems if it fails like colder temperatures can.
I think there will be a variety of possibilities including cold mausoleums certified to work well by the Brain Preservation Foundation, Nectome’s storage, etc. My main issue would be certification by the Brain Preservation Foundation or some other suitable org, because you can mess up preserved people with the wrong temperature.
All that being said, if Alcor had the ability to store at −32°C and offered a good price, and was certified and people wanted it, I don’t see why not? But initially we’re going to offer our own storage solutions by default so we can make sure that quality is maintained.
When do you expect to begin offering these services? Like, if someone dies at time X, and is signed up with you and goes to Oregon and does it all correctly, what’s the earliest X for which you can preserve them?
I’d say 75% confidence on July 2026, 90% confidence on December 2026. Most of the uncertainty is around the timelines on annoying finicky regulatory stuff, like zoning on our location and making sure we’re in full compliance with rules on final disposition of bodies.
Thanks. When would you give 25% by? Also, is it the same for dogs, or is that earlier due to less regulation? And what do you charge for dogs? Double also, would you take bets about the “90% on Dec 2026”?
I’d give over 25% that if someone who’s signed up with us told us now that they had a month to live, we’d be able to accelerate timelines enough to preserve them.
For dogs we’d just need enough notice to make sure our vet has availability and our chemicals are in stock. Cost varies depending on the size but I’d ballpark somewhere very roughly around $50k, obviously happy to talk more details about particular animals.
Sure, happy to bet; I’d want to operationalize carefully. There’s a few different questions here and I expect the timelines to vary a little. In particular, I expect that if we have a terminal customer we go out of our way to accelerate things—setting up for preservation in our lab instead of a nicer facility where people are happy to bring their families, for instance. I’m less certain than that about when we cut the ribbon on the final location, complete our self-imposed certification process, and so forth, just because there’s a lot more moving parts.
very cool! always exciting to see new stuff in cryonics. i’m curious to hear takes from people who know more about the details of the technology what they think of these new techniques.
I’m also excited to hear the community’s takes. I think you’re going to enjoy “Nullius in Verba” whenever that comes up in the sequence—we’ve gotten some opinions from independent experts whose opinions you might value.
I made some Manifold markets to bet on Nectome!
Will Nectome preserve at least one human by the end of 2027?
Will Nectome still be operating in 2032?
Will Nectome have a legally separate nonprofit dedicated to storing patients by the end of the year?
Will Nectome perform 1,000+ brain preservations in a single calendar year before 2040?
Will Nectome’s human preservation protocol be published in a peer-reviewed journal by end of 2028?
Let me know if you have an idea for a market and you want me to make it.
Oh, I love these. Thanks so much for doing them! (Off to make myself some imaginary money...)
Is there any hope/indication that this process can be reverted? For example, has this ever been reverted in a single cell? Or do you think this treatment is only relevant for uploading?
Let me take this one, and also briefly introduce myself. I am Borys Wróbel, Nectome’s chief scientist.
In principle, crosslinking with aldehydes is a reversible reaction. Strictly speaking, a bunch of reactions, all reversible, is involved. But “reverting” the process of fixation at the level of cells and above (organs, whole organisms) in the sense of bringing these biological entities back to biological life is likely to require a similar level of technology as nanotechnology required to “revert” the damage caused by current cryonics practices. In particular, “traditional cryonics” after short postmortem intervals leads to severe brain dehydration “undesirable because of mechanical distortion and toxic effects of concentrated salts”. This is a direct quote from the paper I co-authored—the main credit goes to Andy McKenzie though—https://www.mdpi.com/2076-3425/14/9/942, which also discusses briefly the issue or reversibility.
I guess the presale is like a bet on Nectome’s future; you have a risk of losing your money if Nectome goes under + risk of being locked in if your preferred provider changes, in exchange for a future discount. At 3% inflation, 20k today is like ~27k in 10 years. I’m curious about the unit economics.
Two points on why it’s such an extreme deal:
1) the presales themselves are limited in the total amount we’ll sell
2) we did the math and that price worked out to worth it for us given (1), and some conservative assumptions on when people would need to use them during the 10-year discount period (if someone uses the discount 5 years in, for example and the preservation market price is $250,000, then they would still pay $112,500 at that time. But yeah, I think it’s a good deal and priced fairly given that people buying it now are taking a risk buying it before we open.
The contract is transferable, so if Nectome becomes successful (many patients in the future) you presumably should be able to recover a large fraction of the contract value at that time.
(Obviously if the procedure becomes cheap then you won’t recover as much, but that’s inherent to the “pay far in advance for a discount on current prices” bet, regardless of your provider preferences changing.)
I know you linked to places that appear to explain it—but can you give the short summary of how your approach differs/what it even is that you are doing? Just reading the post makes it unclear—do you still pump them with cryoprotectant and then cool? Do you chemically fixate the brain? Third thing?
We do both! The aldehydes chemically fix the brain (this is the big thing that sets our approach apart) and protect it from being damaged by the cryoprotectant. At that point it’s stable at room temperature on the scale of weeks to months. Cooling it down to the long-term storage temperature extends that time to centuries.
Are the preservation and the discount card both fully transferrable, not just in the sense of [designating someone else to be preserved], but [designating someone else to control them as if they’d bought them] (so that they’re resellable assets)?
[Designating someone else to be preserved] is built in by default. [Designating someone else to control them as if they’d bought them] isn’t present by default but is the sort of thing we’re happy to work out on an individual basis if it’s important to you.
We definitely intend them to be resellable assets and expect to see a secondary market. If some early supporters buy extra 100k preservations and flip them for 200k in six months, we’ll be very pleased about that.
Assuming you don’t do this until you are terminally ill, what is the chance of having enough time to plan this, rather than needing emergency service?
Obviously we’d encourage people to plan ahead, but also, most people don’t die suddenly—slow declines are vastly more common. Personally, when I think about people I’ve known, almost all of them knew they were reaching the end well in advance.
Slow declines aren’t always synonymous with losing hope for a substantial recovery (or recovering enough so that death doesn’t seem to be imminent). In the case of my late wife, there was a clear path to recovery: become healthy enough to have kidney transplant surgery (obesity makes the surgery itself much more dangerous, and there were other issues too), which would likely have solved a lot of her most severe problems. (I immediately volunteered to be a living donor; we had the same blood type, but I never found out if I was otherwise qualified to be a kidney donor.)
Nectome is fantastic! The crosslinking approach made sense to me the second Aurelia explained it to me last year. Better preservation through better chemistry. And even with the 12 minute window, I know they are actively developing systems to make that operationally doable in real world settings.
My question is about the policy and adoption side. Aurelia mentions the end goal of making this part of standard end-of-life care, even Medicare. What does the lobbying and regulatory strategy actually look like right now? Who are the key stakeholders you are working with, and where do you see the most tractable near-term wins: state by state MAiD expansion, insurer conversations, medical establishment buy-in?
Very happy to see an advancement in cryonics, and would use Nectome if I was expecting to die, but I don’t see why I’d buy the 100k pre-sale besides as a charitable act. Most people expect to die in 10+ years, and 100k grows to ~200k in the market, and if the company succeeds, you’ll probably lower prices by quite a bit anyways. Your net marginal cost must be a lot lower, isn’t it?
Maybe at the current stage, these pre-sales should come with a stake in the company: investing 100k with a perk of getting cryopreserved at net cost (if needed) would sound much more compelling I think.
I see a lot of people quoting this $100k number. But it’s only $20k, if you expect to live 10+ more years!
how is using cryoprotectant and storing at lower temperature better than using fixative and storing at room temperature?
how does that compare with sparks brain preservation’s method?
Hi Aurelia! I think the recent news about the “uploaded” fruit fly (mentioned in a previous comment) add to the available evidence (without proving, at least not yet) that your brain preservation method works.
But $250K seems too much to me. Many people who would otherwise be interested couldn’t even consider it. For example I couldn’t, not without winning the lottery.
I hope, however, that advances in technology and reductions of operational costs will make this a viable option for younger people.
Is the email address I have to you still valid, or do you have a new one?
$250K is also too much for me at present, although I hope Aurelia / Nectome have something like (the first 3 steps of) Tesla’s old secret master plan
Exactly! This was the case for Teslas, mobile phones etc. so I guess it will be the case here. Too bad radical price reductions won’t arrive in time for most older people. Bot I’m happy for younger people!
The email address should still be valid! And anything directed to hello@nectome and intended for Aurelia will make it to her eyes as well.
Our goal is of course to reach as many people as possible; we’re all in this because we want humans, generally, to be preserved. If this is something covered by medicare in ten years, I’d consider that a huge victory. Now, that’s a very ambitious goal, but I don’t think it’s theoretically infeasible! End-of-life care is already very expensive for insurers.
Very cool progress in cryopreservation!!
Questions:
Do you foresee any promising paths to undoing your process without destructive scanning?
Is there any major damage you weren’t able to prevent that you think could be prevented with later research?
What are your plans for long term sustainability of your company? (If a better method is developed by someone else and you go out of business….)
I have not seen discussion of S risks related to this subject, which I think is a huge omission, even if only from a utiltarian perspective.
If there is even a 2% chance that a misaligned AI / autocratic government will utilize preservation and life extension technology (of any kind, including mind uploading, if possible) to make one suffer hellishly for a billion years, how does this change the picture? Should one prefer death? Should one make sure their brain connectome is disintegrated after death just to make sure? Or go forward with it?
For individuals longevity and immortality are great. If you can live without your time, friends and family and cope with that.
For civilizations and in terms of fairness, this is probably terrible.
I’m hearing from this that it’s really terrible to go to the future as a refugee, severed from your community and family. I wholeheartedly agree. I think we can do better and make it not terrible or unfair, but an act of love.
There’s a story about Round Up, the weed killer, I don’t know where I heard it before but it’s been important for me. The chemical company produced a chemical that kills a lot of different plants. Some of them were plants that interfere with crops, some of them were pretty white flowers. They called that chemical a weed killer, painted pictures of all the plants it killed on the bottle, and confused the idea of a “weed” with “whatever this chemical kills” so they could sell more bottles of chemicals. But the flowers are still beautiful, and we wouldn’t consider them weeds if they weren’t on the bottle of weed killer.
I’ve made a chemical process that preserves some things and not others. I can capture the synaptic connections and proteins in a person’s brain and archive them for a century with no problem. There’s a temptation to say that I capture “everything” about a person with this method. Do I really preserve all the memories in a brain if I preserve all the synapses? It’s tempting to say yes and in many important senses I do capture “all the memories”.
But consider an old couple that’s been married for 50 years, talking about their lives.
One of them says “Oh yeah it was back in that small cabin with.. what was his name honey?...” And then the response comes back, as it has for the last 20 years, and repairs the gap. In which brain does the complete memory live, if it takes two together to recreate the story?
I would argue that as you become emmeshed in a community, you externalize your memories: sometimes to other people as a call-and-response. Sometimes through smells or your physical surroundings.
One of my friends who’s a student of Roman history tells me that Romans used their houses to remember important things in their life. Rearrange the house, damage the memories.
There’s a kind of glue that I used to play with as a kid, but they don’t make the glue anymore. I’m sure if I ever smelled it again, I’d remember something important. Lots of memories are tied strongly to smell. But if I’ll never experience that smell again, do I really have the memory still? The connections are there in my brain, but they are keyed to an event that will never happen again.
Aldehydes can preserve a person physically, but if you sever a person from their community, environment, family, for some of those memories it would be like encrypting a hard drive and throwing away the cryptographic key. It’s like the weed analogy—the things my chemicals preserve are not the final boundaries of what a person is, and it’s a mistake to confuse the two.
But the solution, I think, is not to despair. We know we will suffer a huge loss if we enter the future alone, so let’s just not go there alone! The more people we preserve from this era, the more context we archive, the more everyone will arrive to the future whole.
That’s why I’m going to fight to make this a new global tradition, as much as I can. I hope that we’ll preserve so many people that we look back to the 1940s and say “that was the beginning of a new era of human history: the era of Living Memory, where humanity finally started to remember in detail what it was like to be there, because it was finally able to keep those people and memories around.”
Finally, in terms of fairness, we already exist in a maximally unfair situation where every single person from earlier generations is gone, unable to participate in the future. That’s not fair to those generations at all. Going from that situation to a world where even a few people form earlier generations can participate makes the world more fair, not less, by my reckoning of things.
What do you think? If we could revive just one person from 20 generations ago, it seems to me that that would be a huge win for allowing that generation more presence in the world and be more fair on net. Do you agree? If not, why not?
How will you ensure that enough poor people are preserved that there doesn’t end up being a movement to destroy the preserved people? I expect this to require there to be many more people preserved who can’t afford it than people who can. If you skip this political cost calculation I expect you’ll end up losing the entire facility eventually due to reactive anger.
Our end goal is to make this become part of Medicare and have it be the default option for end of life care. In other countries, we hope it will become part of their standard healthcare offerings as appropriate. I hope the discussion about how to make preservation a reality for everyone (including many animals!) happens soon, and I think it will as more progress in uploading makes it clear that preservation is likely to work.
But I also want to really engage with your thoughts on this, so I’d love for you to respond to the following, which I think is a crux for me:
Suppose the worked the way you’re modeling it, with a high likelihood of my preservation facilities being destroyed because of reactive anger triggered by a top-heavy income ratio of preserved people. If that was true, I’d expect a lot of stories, today, about people storming and destroying various gated communities, graveyards with predominantly rich people buried in them, corporate headquarters, private hospitals, rich people’s yachts, etc. I don’t really see any stories about that happening. So I predict it wouldn’t be likely to happen for Nectome long-term care facilities, since there’s more obvious targets that would have been attacked first and haven’t.
I’m assuming people would be reacting to a belief that the tech mostly works, even if they disclaim that belief. The current equivalent is urinating on graves, which involves a revealed belief that the dead are actually dead.
I’m hopeful your plan for broad accessibility works out! I’m skeptical it will be possible in many countries due to the current structure of the network of “power” (agreements, enforceability, threats, laws, money, etc) of groups like insurers and militaries and etc folks who profit from death.
Generally I’m not optimistic that rule of law will be back any time soon or that people with lots of power are sufficiently reflective to notice and fix if they’re avoidant of working through how to turn their professed care for everyone into action on it; in some cases I think this may be because they are lying to others but not to themselves. Which I expect to turn into a general malaise of difficulty achieving your goals here.