Does OBP plan to eventually expand their services outside the USA? And how much would it cost if you didn’t subsidize it? Cost is a common complaint about cryonics so I could see you becoming much bigger than the cryonics orgs, but judging by the website you look quite small. Do you know why that is?
Thanks for your interest!
Does OBP plan to eventually expand their services outside the USA?
In terms of our staff traveling to other locations to do the preservation procedure, unfortunately not in the immediate future. We don't have the funding for this right now.
And how much would it cost if you didn’t subsidize it?
There are so many factors. It depends a lot on where in the world we are talking about. If we are talking about someone who legally dies locally in Salem, perhaps a minimal estimated budget would be (off the top of my head, unofficial, subject to change):
- Labor cost of brain preservation = ~$500-1000
- Cost of chemicals, disposable equipment = ~$100-300
- Cost of death certificate, cremation, funeral services fees for the rest of the body = ~$1000-1500
- Long-term preservation cost = very difficult to estimate, depends on economies of scale, and other factors, perhaps ~$1000-2000
These are rough estimates. But generally speaking, there is a reason that many brain banks around the world are also able to allow people to donate their brains for free. There are many many thousands of brains preserved in this way throughout the world. It is not nearly as expensive as traditional cryonics. Here is some more information about costs for similar type of procedure from the Brain Support Network: https://www.brainsupportnetwork.org/brain-donation/brain-donation-faq/
Cost is a common complaint about cryonics so I could see you becoming much bigger than the cryonics orgs, but judging by the website you look quite small. Do you know why that is?
I don't know. A couple of guesses are that we are just getting started and not really doing any marketing because our focus is on researching the preservation methods. Also, it is likely that many people are skeptical of the preservation methods that we use, since they are new and different than others, as well as being experimental. Here is some more information about our research program, which you might find interesting: https://osf.io/preprints/osf/c28hm
I, personally, have a lot of hope for CLARITY style brain preservation and clarification. After formaldehyde fixation, or congruent with it, a plastic gel monomer is introduced. Once the tissue is fully saturated with the fixative and the gel monomers, the gel monomers are 'activated' and link up to form a robust plastic matrix. Then the fats can be dissolved with a gentle soap mixture and washed away. What remains is a foggy haze of crosslinked proteins suspended in clear gel. Very robust, more so than just formaldehyde fixation alone.
The proteins can now be temporarily labeled with removable fluorescent tags, and laser microscopy used to image through thick slices of the gel. Great for 3D reconstruction of the positions of many different proteins.
We discuss the possibility of fluid preservation after tissue clearing in our article:
An alternative option is to perform tissue clearing prior to long-term preservation (118). This would remove the lipids in the brain, but offer several advantages, including repeated non-invasive imaging, and potentially reduced oxidative damage over time (119).
And also in our fluid preservation article we have a whole section on it. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058410/#S7
I'm not sure why this option is much more robust that formaldehyde fixation alone. I haven't seen any strong evidence for that. I do agree that it is potentially very useful for 3D reconstruction, but reconstruction is a much different problem than preservation.
Ah, I mean, robust as in physically robust. The plastic gel that results is quite sturdy. The embedded clarified tissue is relatively easily handled without damaging it. Just my impression from having worked with fresh human brain tissue (delicate), cryopreserved-only (also delicate, in some ways even more so since the cold causes it to stick to tools and surfaces when handling it. In other ways, such as the glassy ice/preservative mixture being firm, not so delicate), formaldehyde or paraformaldehyde fixed (sturdier, relatively firm instead of mooshy, relatively easy to slice cleanly and deliberately), gel embedded (quite sturdy), hard resin embedded (extremely sturdy, appropriate for super thin slicing for electron microscopy).
I realize that reconstruction is a different problem from preservation, but if your goal (like mine is) is to preserve in such a way that you facilitate reconstruction, this seems like a big win.
Imagine, for instance, you must evaluate whether the reconstruction technology is sufficiently advanced to attempt to do a reconstruction for a particular brain. The threshold for 'good enough tech to make an attempt' is much lower if the brain is already prepared in a way (e.g. 1 cm thick slices of clarified stabilized tissue) such that it can easily be non-destructively imaged now, and then imaged again later if need be. A cryopreserved brain, on the other hand, needs to wait until you are very sure that the tech is good enough to handle it. Subjectively, I would feel quite reassured by my chosen method of brain preservation being:
1) stable at room temperature, and relatively robust to less-than-exquisitely-careful handling
2) ready to be non-destructively and relatively cheaply imaged, such that it would be an easy call to make a first attempt
3) preserved in a form that would facilitate reconstruction and multi-protein labeling
Thanks for the clarification and your thoughts. In my view, the question is to what extent the polymer gel embedding is helpful from the perspective of maintaining morphomolecular structure, so that it is worth the trade-off of removing the lipids, which could potentially also have information content. https://brainpreservation.github.io/Biomolecules#how-lipid-biomolecules-in-cell-membranes-could-affect-ion-flow
You are in good company in thinking that clearing and embedding the tissue in a hydrogel is the best approach. Others with expertise in the area have suggested the same thing to me. I'm just not convinced, so I think that more research is required to tell whether that is the best approach.
ETA: Sorry, just saw your edit. Interesting thoughts on the interaction between preservation and reconstruction. Your perspective and goals make sense to me, although it is not exactly what we are pursuing at Oregon Brain Preservation. We are agnostic as to the potential method of revival and expect this to be relatively further away in the future, if it ever becomes possible.
1Yes, more research definitely seems like the best answer to me too.
I'm hopeful that some of these open questions about the relative efficacy of various techniques, and about how to image and then process the data, will be resolved before I'm on my deathbed and need to make a final will / living will.
Do you know if fluid preservation preserves the DNA of individual neurons?
(DNA is on my shortlist of candidates for where long-term memories are stored)
This is an important question. While I don't have a full answer, my impression is that yes, it seems to preserve the important information present in DNA. More information here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058410/#S4.4
1Is that thought one that is generally shared for those working in the field of memory or more something that is new/cutting edge? It's a very interesting statement so if you have some pointers to a (not too difficult) a paper on how that works, or just had the time to write something up, I for one would be interested and greatful.
I have no idea, but I wouldn't be at all surprised if it's a mainstream position.
My thinking is that long-term memory requires long-term preservation of information, and evolution "prefers" to repurpose things rather than starting from scratch. And what do you know, there's this robust and effective infrastructure for storing and replicating information just sitting there in the middle of each neuron!
The main problem is writing new information. But apparently, there's a protein evolved from a retrotransposon (those things which viruses use to insert their own RNA into their host's DNA) which is important to long term memory!
And I've since learned of an experiment with snails which also suggests this possibility. Based on that article, it looks like this is maybe a relatively new line of thinking.
It's good news for cryonics if this is the primary way long term memories are stored, since we "freeze" sperm and eggs all the time, and they still work.
I find this rather exciting -- and clearly the cryonics implications are positive. But beyond that, and yes, this is really scifi down the road thinking here, the implications for education/learning and treatment of things like PTSD seems huge. Assuming we can figure out how to control these. Of course I'm ignoring some of the real down sides like manipulation of memory for bad reasons or an Orwellean application. I am not sure those types of risks at that large in most open societies.
I can't speak for Adele, but here is one somewhat recent article by neuroscientists discussing memory storage mechanisms: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0261-6
DNA is discussed as one possible storage mechanism in the context of epigenetic alterations to neurons. See the section by Andrii Rudenko and Li-Huei Tsai.
Thanks. Just took a quick glance as the abstract but looks interesting. Will have something to read while waiting at the airport for a flight tomorrow.
I first learned about cryonics when I read Eliezer and Robin's posts about it on Overcoming Bias years ago. I got cryopilled. Somewhat amazingly to me, I'm now a researcher in this field. So I thought this community might be interested to know that I was one of several co-authors on a paper just published in Frontiers in Medical Technology, titled "Structural brain preservation: a potential bridge to future medical technologies".
In this paper, we propose reframing cryonics as a type of structural brain preservation, focusing on maintaining the brain's physical structure that encodes memories and personality, rather than making the focus about low-temperature storage per se.
We explore what brain structures likely need to be preserved to retain long-term memories and other valued aspects of personal identity. We then review different methods of brain preservation, including cryopreservation, aldehyde-stabilized cryopreservation, fluid preservation, and fixation followed by polymer embedding. The paper also discusses the two most commonly discussed potential future revival technologies, i.e. molecular nanotechnology and whole brain emulation.
We argue that this structural preservation framing may be more technically grounded and agreeable to mainstream researchers than some of the traditional ways that cryonics has been discussed.
As a personal reflection here, I want to briefly discuss the idea of fluid preservation, which is one topic discussed in our review paper. I remember first reading about this idea in approximately 2017 on a cryonics mailing list. Even though I was already sold on the idea of aldehyde-stabilized cryopreservation -- using fixation as a short-term bridge to cryoprotection and cryopreservation, I remember thinking that the idea of simply leaving the brain in fixative solution for the long-term was bizarre and outlandish.
Around 2020-2022, I spent a good amount of time researching different options for higher temperature (and thus lower cost) brain preservation. Mostly I was looking into different methods for embedding fixed brain tissue in polymers, such as paraffin, epoxy, acrylates, or silicon. I also studied the options of dehydrated preservation and preserving the fixed brain in the fluid state, which I was mostly doing for the sake of completeness.
To be clear, I certainly don't want to make it seem like this was a lone wolf effort or anything. I was talking about the ideas with friends and it was also in the zeitgeist. For example, John Smart wrote a blog post in 2020 about this, titled "Do we need a noncryogenic brain preservation prize?" (There still is no such prize.)
In 2022, I was reading various papers on brain preservation (as one does), when I came across Rosoklija 2013. If I recall correctly, I had already seen this paper but was re-reading it with a different eye. They studied human and monkey brain tissue that had been preserved in formalin for periods ranging from 15 months to 55 years, using the Golgi-Kopsch silver staining method to visualize neuronal structures. They reported that even after 50 years of formalin fixation at room temperature, the method yielded excellent results. In particular, they had this figure:
That's a picture showing well-impregnated neurons with preserved dendritic spines. Looking at this picture was a viewquake for me. I thought, if fluid preservation can preserve the structure of the 1-5% of cells that are stained by the Golgi–Kopsch method, why not other cells? And if it can work in this one part of the brain, why not the whole brain? And if it can do it for 50 years, why not 100 or 150? Chemically, it is not clear why there would be differences across the tissue. Aldehydes crosslink biomolecules in all parts of the tissue. And I already had decided that cell membrane morphology is likely one of the most important structures for encoding the information about long-term memories in the brain. I immediately told one of my friends in the lab I was working in about it.
More research into fluid preservation led to a separate publication on the topic. There are some complexities, but I personally haven't yet found anything which convinces me that this wouldn't work. Fluid preservation has advantages in terms of demonstrated stability for years in brain banks and cost-effectiveness. Because it is so inexpensive, Oregon Brain Preservation (where I work as a researcher) is currently able to offer this service for free in Washington, Oregon, and Northern California, as part of a research study in which very small biopsy samples would also be taken to measure preservation quality.
I want to make it clear that I'm still not sure whether fluid preservation will work. More research needs to be done on it. It is experimental. Personally, I would argue that all contemporary options for brain preservation in humans are experimental. Perhaps the two main points of the review paper we just published on structural brain preservation are that (a) contemporary methods for brain preservation -- including cryopreservation -- are reasonable, but that (b) more research should be done on it to attempt to corroborate the idea of structural brain preservation, better figure out whether it could work, and improve the preservation methods.
Thanks for reading this post. If you're interested in helping with any efforts in this field, please let me know because we could certainly use the help. Simply reflecting on the topic and potentially discussing it with others -- if you think it is a valuable idea -- is probably one of the most helpful things that you can do, because the topic is still very much considered "weird".