Verifiable brain preservation

Adam Ford (AF)

Ken Hayworth (KH)

AF: We have Ken Hayworth with us today. We will be talking about one way of getting to the future, which is medical time travel. By way of introduction, there's me, Adam, I am the host, and Kenneth Hayworth, who is with the Brain Preservation Foundation. He is currently at the Howard Hughes Medical Institute, Janelia farm research campus. He did postdoc research at Harvard. He also invented high-throughput volume imaging of neurocircuits at the nanometer scale. He has built several automated machines to implement this process. He has a PhD in how the human vision system encodes information about objects. Having accomplished what he has and being a vocal advocate for brain preservation, I thought it would be interesting to get Kenneth back on the show.

KH: Thank you Adam.

AF: In a nut shell, we're going to be talking about brain preservation. Why do it? What is it? We will discuss the small mammal brain preservation prize and its significance. We will talk about aldehyde-stabilized cryopreservation and we will talk about large mammal brain preservation and what might come after that. And some questions submitted by Randall Koene and Keith Reily on viability and cryonics. Anything about your background you would like to highlight?

KH: I have a wonderful wife and 2 wonderful kids.

AF: Fantastic.

KH: I can die happy even if all this doesn't work.

AF: Hopefully you have signed up for a form of cryonics.

KH: I haven't signed up for any cryonics. The reason why I haven't signed up for any cryonics currently is because there is nobody out there that I consider to be able to show that they are going to do a credible job. Just like if I had a heart attack and bent over right now, I would want to be taken to a professional hospital with professional doctors and it's regulated and the techniques that they use have been demonstrated over and over again in animal models... I wouldn't expect anything less than that for a brain preservation procedure or cryonics or otherwise. To my knowledge, there is currently nobody out there that has demonstrated that they are doing even a remotely good job at this. I remain to be convinced. I hope that what will happen from our prize being won and other research is that the scientific and larger mainstream medical community will start researching this and developing this in earnest so that it could be rolled out to local hospitals.

AF: Somewhat controversially, you used to be a member of Alcor. Partly the reasons that you just described, the process there wasn't evidence-based.

KH: So, well... for instance, I am a big fan of cryonics in general. I think the idea of cryonics is kind of brilliant if you will. It is a way of taking a sure-failure, everybody is aging, everybody is going to get diseases and everybody is going to die. And we're really not that close to curing aging, from what I've seen, in our medical technology. So everybody out there is going to die, essentially. But here comes this idea that we could pause time, we could have medical time travel if we could just preserve somebody in a static state so that they could get to medical technology in the future that could bring them back. I thnk that idea was brilliant when it was come up with in 1960s. But this does not mean that your cryonics companies or cryonics methods today or decades ago were good in any way. And so, yes, I was enthusiastic about cryonics. I signed up for what I considered to be the largest most responsible organization in this, which was Alcor, and I pretty much immediately asked so how is my brain going to look? What is my brain going to look like? Give me the evidence. Will it destroy the neural circuitry of the brain? I got some reasonably hand-wavy answers pointing to some papers that were not talking about whole brains but were talking about half-mm slices of hippocampus. These were interesting papers and promising, but it wasn't a whole brain. There were some brains showing some low magnification electron microscopy (EM) images, but it didn't say how the brain would look, and crucially whether the connectome that encodes our memories and personality whether that was damaged or not. So this, yes I was an alcor member, but the Brain Preservation Foundation and its prize that I put forward-- that was kind of a challenge I put forward to cryonics organizations for anybody out there and scientists to show that cryonics does preserve the brain, not that it works. When most people out there say "oh, you know, does this show cryonics works?" well of course that has not been done at all because that would require something coming back to life, it would require resuscitation and we are incredibly far away from that. I was never under any illusion that today's technology was anywhere close to that. But that's not really the idea of cryonics. The idea of cryonics is to preserve in static form with sufficient fidelity so that 100 years from now perhaps you could be reanimated. So the question is what level of preservation can we get to today? The prize 5 years ago was a challenge to cryonics companies and anybody else to show that they could do it. The cryonics companies did not, the cryonics organizations did not enter into the prize. They didn't exactly give any additional evidence of connectome preservation of their techniques. But I was very lucky to have the best cryobiology company in the world, probably, 21st Century Medicine, to actually compete in our prize. What they did is they applied what is probably the best vitrification technique that companies in cryonics use. And that did not meet the criteria that we had set. Does that mean it destroys everything, of course not. But they were able to show it had no ice formation, which is very good. But it turns out these particular vitrification protocols will shrink the brain tissue dramatically. That shrinkage doesn't necessarily mean there's damage, but if you look at the micrographs, it seems to be hiding a bunch of other damage that can't really be addressed because of the shrinkage. I gave you a link to one set of electron micrographs on the Alcor website that kind of is there hey this is what we offer. And I find those micrographs to be rather, disappointing. As a neuroscientist, I show these to my neuroscientist colleagues and they say what the heck is this, this is not the type of brain tissue that we expect and this is not impressing us. So they could not win the prize with that. To my knowledge, this is what cryonics has to offer us today, they can offer highly shrunken tissue which may or may not be causing damage, but they have not been able to prove it's not causing damage; there are some other older techniques that were published that go back much further, where the electron micrographs look cleaner to the eye but there's significant ice damage. So what protocols might be good or bad? That was really the state of cryonics that was out there. So, then, because we put forward a prize that was saying forget about this revival stuff, that's near-about impossible right now, so just forget about it. We really want to see that the brain structures that are encoding memory, that those are preserved across an entire brain. Pull out every stop you can, to get to that goal. So this is what 21st Century Medicine did. Researchers Robert Mcyntire and Greg Fahy took out the big guns okay they said we're going to hit the brain with the best chemical fixative, even though its' deadly, the best chemical fixative that electron microscopists use routinely for producing good micrograph images. So they perfused the brain directly with gluteraldehyde. And like I said, this is deadly, a deadly chemical. It crosslinks all the proteins together. It has the advantage that it almost instantly stops all metabolic decay and locks the key proteins of the neurons in place. It also stabilizes the vascular system, the blood vessels, to allow the following steps to occur at an optimal rate. They did this perfusion of the brain, which people have been doing since 1960s for electron microscopy research; then they said geeze if we just leave it in a glutaraldehyde fixed state, there would still be liquid and reactions and... let's apply our vitrification technique to that. Perfuse it with high levels of cryoprotectant agents, 65% weight per volume of a cryoprotectant agent, they perfused that through the vascular system over the course of 4 hours at room temperature. And this is great because it actually very uniformly gets into everything, replaces a large percentage of the water and it's so highly concentrated that this cryoprotectant agent-- they can take the whole brain or the whole head and put it into a freezer unit and store it at -135 celsius so it's solid, no ice formation, time has essentially stopped for this brain. I look at it this way. This is the-- they pulled out the big guns. They took the best chemical fixative, they immediately after that took the best cryoprotectant method, which is super high concentrations of ryoprotectations that so high you have eliminated the possibility of ice formation. Then you store it in a solid state, not a liquid state. They tried that. You might imagine this could cause serious destruction of the brain. So then they had to test, what destruction did this cause? Did it work? They re-warmed the brain, they removed the cryoprotectant agent, they showed that it can be done by perfusing out the cryoprotectant agent, or by slicing up the brain and removing the cryoprotectant agent by simple diffusion. But either of those methods, you can then take that brain and slice it up and prepare slices for electron microscopy, and they showed in their paper that the micrographs look beautiful. They are not shrunken. They look like textbook quality micrographs. Once they published that, I went there witnessed the whole procedure, took back brain samples from them that I knew had gone through the procedure including the storage, and ran extensive electron micrograph surveys both 2d surveys and 3d electron microscopy on it. You can see the connectome, you can see everything. That's aldehyde-stabilized cryopreservation and it met the criteria that we laid out in the brain preservation prize which was that the structure of the brain that we think encodes memory and personality has that been preserved in a way that could last for hundreds of years.

AF: So the structure of the brain that is preserved, is that just the connectome? Are there other factors that have been successfully preserved properly?

KH: The only thing that we were testing was the connectome. The nature of this procedure, and it's a great question because the nature of this procedure is essentially aldehyde perfusion and then cryoprotectant to get it to a cold storage state. On a separate set of experiments, they've taken half-mm hippocampus slices and without aldehyde okay, and have put those through the same type of vitrification process. The same types of cryoprotectant agents and re-warming. They showed that this was compatible on this half-mm thick slice with recovery of function and even electrophysiology, again on a half-mm thick slice, very different from a whole brain. The reason I bring this up is because the cryoprotectant agents are extremely benign chemically. They replace water and they can be sucked back out. So the chemical damage that occurs to the brain can really be localized to the aldehyde step, to the glutaraldehyde fixation, which is extreme-- fixation is basically embalming fluid and it definitely kills you. A glutaraldehyde perfused brain, okay, what damage does that do? Does it preserve the connectome? Glutaraldehyde perfused brain has, you can do immunochemistry on it to show the proteins at particular synapses. If you wanted to know if this had glutamate receptors, what type of ion channels were in this neuron? That type of analysis is compatible with glutaraldehyde perfusion. There's every reason to suspect that these glutaraldehyde cryopreserved brains are not only preserving the connectome but also the structural elements of the connections between neurons, but are also storing most of the chemical information that you would associate with synapses and neurons.

AF: Okay.

KH: that's something I would very much like to see expounded on in a dedicated paper.

AF: Is anybody working on that?

KH: I'm trying to work with the lead author, Robert Mcyntire on setting up something like that. There's funding issues amongst other things. It seems like a logical thing to do, right now I'm not too worried about it because there are existing papers in the literature that show that essentially what should be preserved. There's nothing new about this technique that should nullify those existing results.

AF: I guess people have some skepticism that they may not have had many years ago... a previous president of the US said he wanted to be preserved in rum or something.

KH: he was never president.

AF: Oh, Benjamin Franklin. But these days you would never hear a president saying such things.

KH: I thought Donald Trump just said he wants to be preserved by this technique?

AF: That would be funny.

KH: I don't want to start rumors.

AF: It's real, man. It's akin to, as people metaphorically say, the burning of the great library of Alexandria, except they are much more personal libraries. Why would somebody want to do this? It sounds gruesome. It sounds alien. There's no conclusive evidence one way or the other, so why would someone want to do this? If they had all the money in the world, why wouldn't they?

KH: This is a personal choice issue. There are a lot of people that would understand or agree on the science or agree on the possibility or agree on what the future has to hold and say, no, it's not for me. Good for them, you know. I may decide the same for myself at some point. But, but I think one way of looking at this. When I was a kid, I used to imagine a scenario or maybe saw it in a movie where what if a portal opened up and it was a portal to the future in 100 years from now. Would you step through that portal? Some people would say hmm, I wouldn't do that, who knows what's on the other side. There might be aliens taking over the world. The whole human species might be dead. Maybe my job knowledge is irrelevant. Okay, fine. There's a lot of people though that might say wow this is a portal to the future and they will leap through it without any question. This is for those type of people that would really find that a thrilling adventure to undertake. Another way of looking at this, and it is kind of amazing, the most of the questions that I get on this are not detailed questions about the science... which I find a little bit disheartening because I feel like that's really where the interesting parts are. It should be up to somebody else, to have different opinions, they have different opinions fine. Some people go for plastic surgery some people don't; social issues like that should be considered the next step, not the first step. These are the types of questions that I get, though. One thing that I find amazing is that there seems to be a lot of people that go right for the argument that human life isn't worth it. Why would we want to have people live longer? There's, you know, the debater in me feels like, yeah you can make an argument for that, why should people want to live? But you have to understand that if you're going to make that argument and you're going to say we shouldn't expand at all to help people live longer, then at the very minimum anyone over 65 years old should not be admitted into a hospital because it's just not worth it according to them. We shouldn't have medical development of tech to help anyone over 65 because they are over 65 that was the cut off right? So there might be logical argument that extending life by this method is not worth it, but that would cut back on what people consider today to be just the bare minimum ethical standard for medical research and treatment.


KH: ... readily had by additional research. If there is debate to be had, many people might say "oh, well, this preservation is not preserving who you are". This is a claim that can be checked. It can be debated. Maybe we don't have the final answer for that, but it's well within the scientific method to argue this.

AF: Sure, yeah. It makes sense to get the science to a state where those sorts of arguments have some empirical backing.

KH: I think to kind of summarize where I think this changes about cryonics, if I can be so bold, okay, how I look at this is that people have been looking at cryonics and saying geeze we don't know what damage is occurring to the brain but it's probably a lot of damage occurring to the brain. And we don't really know how somebody is going to be repaired by that. But it's better than a zero chance. And so if you ask people within even the cryonics community, what chances do you give to this technique working in the sense of a preservation technique is good enough to bring you back if anybody cares to bring you back in the future. Leaving societal things out; is this preservation technique good enough? People tend to give like 5-10% chance, maybe 1% chance. There's a lot of people that give-- that sign up for cryonics and they will say well I only give it a 1% chance but that's better than 0% chance. So I look at the aldehyde stabilized cryopreservation technique and I weight that by what it has demonstrated now in the open scientific literature and what is being preserved there, I weigh that against what we know about the brain; we don't know 100% about how the brain works, but we have good models about how memory is formed and we have secondary and tertiary models for memory if the first ones aren't right. Aldehyde cryopreservation seems to meet all of these models. You have to get very far from these standard models to the point where aldehyde preservation doesn't actually preserve the structure. So I would put this at 99% chance that if you get aldehyde preservation that if anyone cares about reviving you in the future, that it's possible. So this should change the mindset. It shouldn't be that you have to get to 100%. It shouldn't be that you have to mind upload someone or bring someone back to life with nanotech... you should be able to get to some threshold, some reasonable threshold of certainly before it gets offered to the public. I think that the brain preservation prize was written essentially to require that threshold having been met. And this technique does it.

AF: Right, and this is a point, preserving to upload or preserving to biologically revive. This is a question that Randal Koene asked. I had a quick question about what we were talking about before... ... about dying and whether cryopreservation is a valid option for people... sometimes this requires you to give up cherished beliefs... is there information here that people just aren't looking at, and does it disqualify on grounds of culture or what they believe traditionally even if they are....

KH: I think the main thing is a really dramatic ignorance about how the brain works. It is, we teach people basic biology, we teach them basic chemistry, let me put it this way. If I said to you, you know, any biology class is going to explain to you that life is really just chemistry... now that's uncontroversial, I could say, you could say that life is just complex chemistry and people say yeah and there's whole books on that.


44m 25s

AF: So if they are the last ones to do cryopreservation, then maybe they are a dying breed. Let's talk about the details of what the small mammal brain preservation prize-- why small mammals first? It is worth talking about this, though. Why has this been significant? Why did 21st Century Medicine win the prize? And maybe the history of the prize. You brought this up in an AMA where you said 21st Century Medicine was doing some pretty amazing stuff back then, so I guess you were predicting that they would do quite well.

KH: The history of the prize is that when we started it was a challenge to any scientist and any cryonics organization. The prize relatively quickly had two competing groups with two very different technologies. Three different technologies, you could say. One group was Shawn McCullough at the Max Planck institute. He had developed a technique, or was developing a technique, for preserving a whole mouse brain using a modification of the standard chemical methods that are used for plastic embedding for electron microscopy. He was doing that anyway because his goal that he is far along on now, is to imagine an entire mouse brain with an electron microscope and get all the connections. It's a humongous goal. Very difficult. The first part of that was well we have to at least prepare the brain in plastic so that it can be sliced and imaged. So he entered the prize because he figured it's a slam dunk I can do this no problem. 21st Century Medicine had been doing a straight cryopreservation technique on rabbit kidneys trying to develop a technique that could where you could store a kidney and then bring it back to life. It was the full-on cryonics that everybody dreams about, and very difficult. They said well gee your prize requirements aren't even saying we have to bring it back to life, we should be able to handle this too, we're using a relatively similar technique that is used in cryonics organizations, we'll enter the prize, it will be a slam dunk. So two groups both thought they had the prize in the bag and they thought each other would have no chance.... so you ask why the small mammal prize, well it's hard enough for a small mammal. The amount of experiments that you have to do, to get the bugs worked out, it's much better to do it in a small mammal rather than a large mammal. So that's why breaking into a small mammal phase and a large mammal phase. The straight cryopreservation technique hit up against this shrinkage problem of the neuropil. And they were not able, although they are still working on this, they were not able to get around this. Sean McCullough's lab had osmium penetration issues, they were using a chemical fixative that they had to use, they ran up into problems. For several years they were trying to work out problems. I would get images and brain backs from people and I would say oh there's damage here there's damage here. I felt like I was contributing a little bit by pointing out things they might not have seen otherwise. In the last year, both of them had high profile publications that showed they had gotten their technique to work on a small mammal and I should say that 21st Century Medicine also showed that it worked on a pig in their paper but only-- this was only after they went to the aldehyde fixation that I mentioned earlier. The dramatic step of fixing the brain with deadly chemicals before cryopreservation. They got their technique to work enough to put out a publication. Sean McCullough got his working enough to put out a publication. And then they had to meet the more strict requirements that the prize had, which is beyond publication, to show that it works throughout a whole brain. It was only the aldehyde stabilized cryopreservation that just recently on a rabbit brain that crossed over the threshold finally. The... there was a mouse brain entry that Sean McCullough put in that looked very good except there was some penetration issues of the chemicals and it caused some destruction of large axon tracks in the middle of the brain and that was enough for us to say nope sorry. I feel a little bit bad because I know if he messed with the chemicals a bit more he could get over that problem.

AF: That's interesting. Even more interestingly, isn't a rabbit brain bigger than a mouse brain?

KH: It's enormously bigger, at least 5x the volume. It was much harder to image. I didn't image the whole thing. I did survey imaging. It's much larger. It really goes to the question because McCullough's technique is based on immersion in chemicals. The initial fixation with glutaraldehyde, which is kind of the standard, he immerses it in chemicals afterwards and then finally immerses in plastic resin that does the final static storage. This has not been able to scale beyond a mouse. He has tried with a rat brain and it's quite difficult. His technique will, there are definitely ways that he could get it to scale larger, but that will require significant research and so he was only ever really demonstrating mouse brains. 21st Century Medicine aldehyde-stabilized cryopreservation technique is all perfusion-based, on the other hand. So because they are perfusing the chemicals through the brain's vascular system, it doesn't matter the size, it could easily work on a whale brain for all that matters. They showed it on a rabbit, then they showed it on a pig, we haven't imaged all of the pig brains, we imaged some of the pig brains. Yes, it's bigger again. It's harder to image, but from a technical perspective, it should be as well preserved as the rabbit brain.

AF: So we've spoken about the small brain prize and from, okay, so the requirements there for passing the test were, you described at least most of them.

KH: It was survey... a brain had to be, we had to see a brain and know that it was put through storage that would allow it to stay in storage for more than 100 years. So that's why you can't just dump it in glutaraldehyde. It has to be shown to be able to stay in storage for more than 100 years.

AF: Without waiting 100 years to do that.

KH: Right. So the reason why aldehyde-stabilized cryopreservation has met this requirement is that they have stored this at a solid state at -135 celsius. Any chemist will tell you, that's not changeable. It will last for 1000s of years as long as nobody pulls the plug. Even if you pull the plug and let it warm up for a few weeks, and then bring it back down again, it doesn't really hurt it. Because it's stabilized, it can be cycled up and down, it really is, like I said, they brought out the big guns for this. This is not just cryonics where if you re-warm it a little bit it's destroyed; no, this is aldehyde-fixed with strong covalent crosslinking of the proteins and then vitrifying it solid. It's very very well preserved.

AF: Excellent. Yes, this sounds convincing to somebody who doesn't know very much about science or cryonics. What should the tests be for starting with the small brain yes, what is the difference between the test that you've, the brain preservation foundation prize for the small brain vs the larger mammalian brain, is there any extra requirements that you have there that would make it more difficult? What's the difference between the prizes?

KH: Besides one small and one as large as a pig; there is one additional requirement that the procedure, so, for instance, these mouse procedures... and even the rabbit procedure, they could have been done in a way where... in a laboratory setting, it's often the case that the... you use several animals to get one. I've seen this happen at least where the technique you use is not going to work every time. You don't really, you don't make sure that the wash-out was done correctly and all these other steps that you would have to do if this really was a patient. And so, in the small mammal phase of the prize, our requirement was that you would get this to work in a lab setting but you don't have to have it be of the type that would work in a medical setting. For the large mammal phase, there was a requirement that it should at least be robust enough that it could pretty directly be applied after that in a, developed into a human medical procedure. I wanted there to be kind of a clean transition between those two that were in the protocol. It turns out that the 21st Century Medicine team because their day-to-day procedure is organ transplants that they have a surgical procedure that works for having to try to make the animal survive. So they oxgenate the animal and they treat it like a surgical procedure, and up until the point that they shoot in the deadly chemical, it's something that you could see as something that is done in a hospital. So there's not much of a difference between the small mammal phase and the large mammal phase from this perspective. We just have to do the imaging and check that the pig brain looks as great as the rabbit brain.

AF: So it sounds like they have the procedure in place to win the next prize.

KH: Right. I went to their facility and collected samples from their pig brain. And also it was in their publication. It was another requirement that the research must be published in a peer-reviewed scientific journal, and they have met this requirement.

AF: So using deadly chemical fixation to stabilize the brain... do you think people, do you think this will be used in the future to cryopreserve patients? Or do you think there needs to be another chemical which is not deadly which does the same thing? Is it logically possible to create a chemical or one that exists such that this deadly fixation chemical could be replaced with something not so deadly?

KH: I am not going to say it's not logically possible, but yeah it's highly unlikely. People have to be realistic. If somebody invents a pill that cures all aging and disease, that would be fantastic, we wouldn't be talking about any of this at all. If somebody succeeded in real cryonics rival where they take a dog and perfuse it with whatever and brought it down to very cold temperatures, stored it and brought it back to life and it walks off the table, we wouldn't be talking about this altogether. The fact is that these are really hard. Nobody is close to getting to it. We're stuck with deadly fixatives to preserve the brain. This locks you into a situation where you're not going to easily bring somebody back easily. It's going to be... maybe 100 years before people have the revival techniques to bring someone back to life. We can speculate about gee wouldn't it be better if they replace us with a magic chemical that can undone, well if that can be undone then yeah that's great. What is the likelihood of that occurring any time soon? Well if we wait for that, there's millions of people that will needlessly die... so I think, so I look at this from a practical perspective. And I realize that, I fully realize that a lot of people hear deadly chemical and that's the end of the story for them. They immediately think it's nuts and it's not medicine, and they think it's brain uploading only, and they think it's all nuts. Okay, that's fine. But, that's not really an argument, that's a gut instinct that is saying I'm going to dismiss the idea that we will have progressed in scientific technology in 100 years from now. That's basically what they are saying.

AF: Is there any particular, I don't know if have thought deeply about this, do you have any possible avenues for non-deadly fixation agents that you could see possibly in 50 or 60 years or even longer, being available or do you think it's just, what we have today is it?

KH: So... I haven't thought very deeply about that. The thing I would like to convey is that if you think about it from a revival point of view, it really is, this is a deadly chemical that locks proteins together, glutaraldehyde. If you think about it from my perspective, as a structural point of view, this is basically a magic nanotech bullet that we have created because it goes in and covalently cross-links just a few of the amino acid types of the proteins. It locks them in place without destroying the actual tertiary structure of the proteins to a large extent. The fixation is so rapid, it stops decay so rapidly, that it really is almost like a magic chemical and it's why for 50 years electron microscopist have called it their best method of preserving the ultrastructure of the brain for the studies they do. It's possible that somebody could come up with something reversible, but I don't see it. I think to a certain extent it would be a holding-out for that would be... would be incorrect.

AF: Where I was heading with this is, what's next, after the large mammal brain preservation prize being won? What is the next frontier for testing? What's the next requirements that you're going to be looking at?

KH: I don't know. The brain preservation foundation was intimately related to this prize. Basically the core mission as I saw it of the brain preservation foundation was to make sure that the scientific community was able to finally cross that threshold of preserving the connectome of a brain. Proving it and putting into the scientific literature and moving the discussion forward. Now that this has been done for a small mammal and at least in the scientific publication for a larger mammal as well, it really begs the question of whether you go-- like you're suggesting, going to a completely different technique that is trying to bring someone back... I would like to think that the next step, from a research point of view, is to ask how well does aldehyde stabilized cryopreservation preserve other things? Like the molecules at the synapses. Does it preserve the conformational states of phosphorolized proteins? There is some evidence that it should; I don't know. Are there ways to improve aldehyde cryopreservation? One of the things dramatically different in one of these brains is that the extracellular space is lost. This is something that is typically lost in perfusion with aldehydes, but there are techniques that people have invented that can preserve extracellular space. These could be combined with aldehyde-stabilized cryopreservation. I see this as the first paper of a technique that I think will eventually be "the" technique that people will apply to themselves in a hospital setting. This might require lots of additional papers and research, I think it will require strong arguments with the scientific community and with the medical community and pointing out that this is a rational thing for people to be able to choose. That's where I see this going. I would like to think that in a few years we will start to see the first really high quality medical application of aldehyde-stabilized cryopreservation, and I would hope that it would not be by unaccountable fringe organizations... which will also probably start applying this, but who knows what you're getting there? Like I said at the beginning, if they were offering heart surgery, I wouldn't want to get heart surgery from them. If they were offering aldehyde-stabilized cryopreservation, well I wouldn't want to get that from Alcor either... you should not apply this to a dead body that has been dead already. You need accountability, controls, checks and regulations. I think the brain preservation foundation is really going to try to help this technique blossom into additional research within the medical and scientific community.

AF: Fantastic. I have some questions. We touched a little about this. Randal asked specifically, Ken what would you advise to people who are most interested in mind uploading rather than cryonics, should we wait for aldehyde-stabilized cryopreservation or should we sign up for Alcor?

KH: I have been on record on this, I posted a blog post recently on this... I think there's a different way of looking at this. These cryonics organizations that are out there... let me give you an analogy. Let's say that I'm a cancer researcher. I have spent the last 10 years developing some cancer drug that has some promise in mice. Okay. And I'm really enthusiastic about it. And then some pardon my french some assholes break into my lab or maybe they don't even break into the lab but they take the chemicals in my published paper that somehow worked on mice I'm claiming, and start offering that for money to cancer patients. Not only would I say, you know, that's not really good.... you know, there should be other checks and balances in place. I don't mean for this to be taken and be applied by a group outside the medical community. Not only that, but I would be fearful as that cancer researcher that if the outsiders botched the application that it would come back and ruin the possibility of my own research eventually blossoming into the medical community to help cure cancer. So obviously this is not a cure for cancer, this is aldehyde-stabilized cryopreservation; I'm not the researcher, it's Robert Mcyntire, he gets the credit as the person who invented it. If I was him, I would be very scared that the techniques I had invented would be applied prematurely... I lost your connection.

AF: We were talking about, yes, so, we had Randall's question, should we wait for ... aldehyde-stabilized technique, or mean-time sign up for cryonics organizations?

KH: I would go further and say I'm very concerned that the premature application of this technique or any other technique could actually slow the eventual and inevitable adoption by the medical community. I don't have any doubt that eventually the medical and scientific community will either cure all aging and disease, or they will eventually come around to the idea of developing some form of cryonics. So eventually this is going to happen. I'm very fearful that the premature application of these outside of the medical and scientific community's consensus, will slow this progress... If cryonics had not been prematurely applied to human patients in the 1950s, 1960s and 1970s, that the scientific community may have kept rolling forward slowly with research and we might already have this option available in hospitals right now. Obviously this is history, I'm not sure, it's just my opinion. I think it's a reasonable possibility that offering cryonics services without the bare minimum of medical and scientific approval is only hurting our cause. This is another reason why I have personally resigned from Alcor. I made that decision quite a while ago because of a lack of evidence. But I'm not anxious to jump into any other organizations like that, in fact if I was given the opportunity... let me make a stronger point. Let's say that I was dying today with a fatal illness and I was dying today, and there was an organization, cryonics organization of Australia I don't know, that was applying aldehyde-stabilized cryopreservation and they were doing it the right way, would I sign up with them and do it? I think the answer would be no. I will die instead. I would rather that the scientific and medical community come to grips with it on their own terms. They should kick the tires on their own. They at the end of the day whether it's 5 years or 10 years from now that it's available to everybody in hospitals in a reliable fashion. I would much rather that occur... even if I die, my loved ones die, or my friends; if our deaths, our deaths are a very small price to pay for the millions that might eventually be saved by a technique if the medical and scientific community actually adopt it. So you're asking that question to a person who is very colored in this area... if Randall is saying gee, I'm going to die tomorrow, which option should I take? I'm saying it doesn't matter; your life is not important compared to what this is. Imagine you were the cancer patient that had just read this article and said wow it works on mice, let's break into the lab and shoot up with this cure. Well this patient should say geeze if I die horribly anyway, it might torpedo a very promising line of research; maybe it's better for me to not get it, even if there's a reasonable possibility of it helping me, because there's a greater social good to be served.

1h 18m 41s

AF: ... able to apply these techniques thoroughly enough, or are they just not accountable?

KH: You could get an organization to do heart surgery, absolutely. But, we, it's not a given. The organizations that I have seen, don't give me any reason to believe that they would apply it properly. I could be wrong about that. But I think that really to a certain extent it's a side-point. What's really important is to get the medical and scientific community on-board. One of the key things is so that a legal determination of death is done away with. Clearly this, even if the technique works perfectly well on a lab animal under ideal surgical conditions where the animal is alive until it's perfused, this doesn't say how well it will work on a diseased animal one that has undergone cardiac arrest and is ischemic for a few minutes... it says nothing about this. So the best way for this to happen would be for the scientific and medical community to adopt this. We have a chance for this to have. Almost everyone I have talked to in cryonics has said never going to happen; scientists don't believe in it, medical community doesn't believe in it, we don't trust them. So what they are saying is that the scientific community can't go beyond their paradigms. I don't think that's true. I have nothing but the greatest respect for the scientific community. It applies its methods, it figures out what's true and what's not true, and it may take a little bit of time, but I think we should be given the opportunity to debate this to absorb it and a chance to move forward. I would like to see, although obviously this is not going to happen, I would like to see a moratorium on the use of this technique, potentially other techniques, to give a chance for the scientific community-- to give a chance to spark a debate in the scientific community and say is it right for us to not have researched this? Is it right for us to force people to starve themselves to death in order to undergo these procedures? Does it make sense that structural brain preservation should be viewed as a potentially life-saving method? Maybe it doesn't make sense, maybe there is magic in the brain. Let's have that debate, let's open it up. I think the larger scientific community, if allowed to have that debate, would almost by definition come to the right conclusion. They haven't been given this chance yet.

AF: So they need to be shocked into starting to think about this seriously?

KH: I wouldn't say shocked.

AF: The existing establishment... the other people in the futurist community, that the independent cryonics outfits are more forward-thinking.. some sort of stagnation until there's a big paradigm shift, like a big paradigm shift going on in the bigger scientific community, will they trust the scientists at that point? So what you're trying to do is give the scientific community to show some interest in this... to show that they can make progress? / KH: If you look at what has been done right now, what has been done so far in terms of aldehyde-stabilized cryopreservation is exactly the same thing that would have been done for a new cancer drug, like a new paper showing that it shows to work on lab animals in a controlled setting. It's out there, people can debate it. Nothing has occurred that is out of the norm right now. It should be developed further. That's the same as with any other cancer drug. The minute that someone comes in offering money to offer it to some individual or some family member that is brought in in a hearse, literally these things happen in fringe groups, that people will drag their loved ones out of morgues, I'm not talking about Alcor, I'm talking about other organizations. They drag people out of morgues and say gee can you apply some whatever technique to this because it gives me a good feeling... That can in my mind that will only cause backlash. It will only shutdown any potential dialogue that we are just beginning to start to have with the larger scientific community. This is what happened in cryonics. We had, think back to 2001 A Space Odyssey. That's what people thought about the future in 1967 or whenever that movie came out. They were thinking gee the science of cryobiology is so fascinating that eventually we will be able to perfect cryonics suspension. That's what the young cryobiologists were thinking about when they were getting into the field, that's the long-term possibility. But then somebody comes in and does a botched job of cryonics and produces people that have ice crystals ripped up their brain and they apply this to human beings...? So either the cryobiologists now have to say either it's a good thing or bad thing; and not only do they say it's not a good thing, obviously, duh, it wouldn't work because of the ice crystals.... but now they have to go overboard and say it's impossible to do cryopreservation of humans and bring them back. It shut down the whole field. Do we want the same thing to happen today? Do we want people to say oh they just shot this person up with glutaraldehyde, those butchers, they don't know anything-- right? So now if you ask the scientific community, if you ask them hey is it okay to shoot people up with glutaraldehyde, they are going to say of course not, it's horrible, no we're not doing that research and we won't allow any of our grad students to do that. We would much rather have them say well it's interesting, it's been shown in lab animals, it seems to be heading in interesting directions for the far future-- that's the response we want from scientists. I am terrified that this will get torpedoed by premature application. There is a specific way to go to the scientific community, and it takes a while and it might seem strange that it has to be done that way, but the original cryonics organizations definitely and completely botched that up. AF: What do you think about the media's coverage of cryopreservation and brain preservation?

KH: There are lots of good articles that got the story right. They didn't sensationalize it, which was great. They said this was the first time a whole mammalian brain has been preserved at the structural level at the scale of synapses and that's it. But I have seen other stories that just have didn't understand anything and yet ran with the story. I saw one story that said rabbit brain recovered! Like it was brought back to life! And it made me upset and I emailed the editor of that publication and I said, you have the most misleading title here. People are going to misunderstand this, they are going to say that the brain was brought back biologically... you have to change the title. It would only take a few minutes to change the title. They refused. They refused for no reason that I could see. All they were interested in were people clicking on their story whether it was right or wrong. I don't have very much faith in the general press. There are certainly a lot of organizations that got the story right and we listed those on our website and tried to pull out the guts of each story that really got the story correct. To show people that yeah this is what journalism can do, they can get the story right without sensationalism.

AF: There's plenty of articles.. I think people believe that the brain was revived in a workable fashion and that people could be sure that cryonics will work just around the corner...

KH: I can tell you that the repudiable organizations like New Scientist and Scientific American covered this and they got the facts right without sensationalizing it right. So it comes down to which orgs do you trust to get the story right in the first place?

AF: Have you had backlash from scientific establishment saying it's ridiculous?

KH: Not yet. Not that I've seen. I shared my images with a lot of my colleagues before this. Obviously these images have been going out to a bunch of neuroscientists just as a double check on what how I feel about these images and whether they show preservation. But no, I haven't yet gotten a significant pushback. And I think the reason is that anybody who looks at our website or that looks at the correct quotes that we have given, we're not sensationalizing this... we made sure that the prize had to have a peer-reviewed publication, and we went the extra mile to get very very good electron micrographs and many of them, to show that this really does meet the criteria of the prize. There's nothing on our website or anything that we've said that says anything about biological reanimation or revival; we go out of our way to say the chemical we use is a deadly fixative glutaraldehyde so obviously nothing is coming back to life. We went the extra mile to make sure we would not get that type of blowback.

AF: That sounds hopeful. Do you predict any sort of bad.. like the image of cryonics feedback from scientific establishments based on what you're doing?

KH: Unfortunately I think that the idea of cryonics in the scientific community has been basically at the zero level for decades. Nothing I can say can lower anybody's opinion in the scientific community about cryonics. The fact that, I ... what I like to say is that this prize, the winning of this prize, is a vindication for the idea of cryonics. It's not a vindication for the cryonics organizations. It's not a vindication for what has been applied to humans so far. It's a vindication of the idea of cryonics because people have said it's impossible to preserve the structure of the brain that encodes memory. There's a famous, infamous article by Michael Schumer in Scientific American over 10 years ago that said that described cryopreservation and cryonics preservation of a brain as like putting strawberries in a freezer and taking them out and they're mush. That's his quote. "That's your brain on cryonics". That was their conception of cryonics, that it just destroys the structures of the brain. Having an open scientific publication that shows glutaraldehyde preserved brain can be preserved and rewarmed and the structures are still there, that's somewhat of a vindication for the idea of cryonics. But it's as good as we can do right now. It's not bringing a rabbit back to life. Michael Schumer has made some recent comments; he wrote to Scientific American.... let me back up. Michael Schumer is a very bright guy. Nothing gets past him. And he was a vocal critic of cryonics. I reached out to him at the beginning of this prize and I asked him to be on the board of advisors for the Brain Preservation Foundation. I described the prize to him and told him what we're doing, this is skeptical stuff, he said if he sees bad stuff he's going to put it out there. To his credit he said yes I'll be on your board of advisors as a devil's advocate. He would point out when I am seeing things wrong, or might be hoodwinked for example. He has been on our board of advisors... more importantly, he was in Los Angeles, and 21st Century Medicine was in Los Angeles, when I was going out there to witness the rabbit being cryopreserved and reached out to him to help witness this. Like a good old fashion James Randy type of skeptic, and he came and both of us witnessed this rabbit being cryopreserved. This is what he wrote in the recent article in Scientific American this month, in his skeptic article. He's certainly not lending his credibility to this, he's still very skeptical of mind uploading, he's skeptical of cryonics as a whole, but like a good open-minded scientific skeptic, he saw that there was enough here that it was not a waste of his time to check into the details and see what the real facts were. So I looked to him and my other scientific colleagues in neuroscience that have started to look at something they would never have looked at before, that they would have spoken out about before. So I think this is showing, demonstrating that there is an opening for these skeptical communities to loop back and re-evaluate cryonics and the whole idea of cryonics in general.