Cryonics, February 1987 Neural Archaeology by Thomas Donaldson, Ph.D.

Recently ALCOR conducted some very important experiments. They are important not because they answer any questions, prove or disprove anything, or even tell us much directly. They are important because they are the very first studies of their kind carried out by cryonicists. They may in fact be among the few studies of their kind at all.

What ALCOR has done is to produce micrographs, both on a light level and on an electron microscopic level, of several different brain regions of dog brains undergoing warm ischemia. That is, these brains were subject to periods of no blood flow and then examined to see the state of the neurons. The periods in question were 2 hours, 12 hours, and 24 hours. Qualitatively, these brains were not in a good state. Mike Darwin himself refers to their contents as "just debris." My own feeling on seeing the ALCOR micrographs is that our understanding is still too rudimentary to draw conclusions. To obscure the matter more, for instance, there is one reference to successful cell cultures of gray matter taken from the human cerebrum 2 to 3 hours after death (Z. Wroblewska, D. H. Gilden et al, J COMPARATIVE NEUROLOGY, 16(3), 295-306 (1975)). DNA will also survive in ischemic neurons for at least 2 hours (N. Becker, AMER J PATHOLOGY, 38, 587 (1961)). All this work needs extension, replication, and clarification.

Not many years ago cryonics experienced a very positive event. Someone from outside cryonics (Eric Drexler) came to understand our ideas on cellular repair and their importance. I think they are important, and I think Eric has done a service in both spreading them around and tying together all the thinking people have done, both in the electronics industry and in biology, about "nanotechnology." What these ideas give us, of course, is some idea about how repairs can be done.

But there is another side to cryonics, and that is the issue of whether the information survives at all. Without the information we can't really think of bringing anyone back, no matter what our technology. (Of course, behind that point about survival of information lies another point, about whether the information is sufficient: just what is this identity we want to preserve. But for purposes of this article, I'll simply say that survival of information is the second fundamental issue with which cryonics must deal).

Many cryonicists might hope for a similar "win" about survival of information to the one we've just had with nanotechnology. I'm going to argue that we can't really expect that "win" until it's irrelevant to us, that in fact the nonexistence of such a "win" is fundamental to the whole cryonics idea.

We would all like "proof" that cryonics will work. There will never be proof that cryonics will work. Certainly, individual people will be revived. Some of them (we hope a very large percentage) will actually come back as the same people as those who "died." There will certainly be proof that we can successfully freeze human brains and definitively preserve personality, identity, the "soul", or what have you. But those things aren't cryonics, they're just particular tech- nologies. They don't really embody the key idea.

The really key idea in cryonics is the idea of freezing (or otherwise preserving) people when we don't know if we can ever revive them. Of course, we intend to figure out later whether we can do this. We intend to succeed in reviving them. But before we've actually done so, we certainly can't prove we will succeed. And funny thing, after we've done so, the proof will be irrelevant. If we know how to bring somebody back as a fully functioning human being after an hour of ischemia, why should we ever bother to go to the added expense and trouble of freezing them first? That would be bizarre and unnecessary.

If you're involved in cryonics, you've got to make your peace with the unknown, because it will always be there. You've simply got to make your peace with it.

Before cryonics, there was "death." After cryonics, there are a host a pathologies. Brains ischemic for 12 hours are one instance of a pathology. We have many others, and yet others piled on top of them. Brains ischemic for less than 12 hours, brains poisoned with cyanide, with nerve gas, with botulin toxin. Brains hacked into pieces. Brains improperly frozen or improperly revived (in that are thousands of different pathologies not yet even named!). Brains fried in radiation. Brains taken over by nanotechnological machines. Brains subject to Gaucher's disease, Alzheimer's disease, kuru, dementia from AIDS, Kreutzfeldt-Jacob disease. . . and so on and on. The cryonics proposal is to treat everyone with these conditions as a permanent patient, until means are found to bring them back.

We do this not just because it is humane and liberating (yes, it is humane and liberating. It's even in the highest tradition of medicine. But I'm not going to argue that). We do it because we know of at least one technology which makes it possible to treat people as permanent patients (I mean permanent). Of course, that technology is cryonic suspension. Currently we know of no other technology, but it won't change matters if another one comes along. It is even likely that another one will come along. But we do have to be clear that the effects of cold are a fundamental empirical premise. We also have to be clear that cryonic suspension isn't the same as suspended animation. It only looks the same.

The word "nanotechnology" doesn't provide us with a magic wand we can wave over all such problems to transform them into a solution. It doesn't do so because the preservation of information will always be a fundamental issue. For most frozen patients we're unlikely to even have proof that their identity survives. This is because the problem of recovering identity isn't the same and can't be the same as the problem of how memory is stored. The second problem is a solvable problem in neurophysiology. The first problem is a problem in nerve cell archaeology: to infer from whatever clues remain at hand what the memory was before. This discipline doesn't yet even exist. It has been inaugurated by the recent ALCOR work

To do neural archaeology it's not just necessary to understand the physiology of memory. Life is not nearly so easy. We have to understand the entire workings of nerve cells and all the other brain cells, to such a degree that we can predict in advance how they will respond if stressed in different ways: by ischemia, by poisons, by radiation exposure, by hostile nanotechnology. We have to understand every single pathological condition, and have a detailed picture of the sequence of events occurring in brain cells subjected to these pathologies, second by second, straight down to total autolysis. This is a fundamentally infinite task. True, the brain is a finite system. But the number of possible stressors and the damage they can cause to it is inexhaustible.

Often in medical periodicals people will publish reflective articles about the future of medicine. They are usually insipid. Well, cryonics is the future of medicine. I don't mean just that people will someday be frozen and that gerontology will rejuvenate us so that we live indefinitely long. I mean that we're going to see a change in boundaries. All of the deaths that we now know of as deaths, and simply abandon, will become pathological conditions, to be studied as problems with the aim of a cure. The future of medicine consists of finding ways to recover poorly frozen patients with Alzheimer's disease and an hour of warm ischemia.

We already have a class of diseases called iatrogenic diseases. These are conditions which result from medical treatments. Antipsychotic drugs, for instance, cause a neurological condition called tardive dyskinesia, which consists of violent facial tics. These conditions are not the same as malpractice, at all. What has happened is that our treatments simply aren't perfect. We'd like to think that we'll have perfect freezing and perfect rejuvenation. But that can't happen either. Even if things go well for most people, for some people things will go badly. They will become medical cases. Some people will go to their doctor for rejuvenation, and wake up 200 years later because they reacted badly to the treatment.

Solving the problem of neural archaeology is like curing or preventing all diseases. It won't happen. (Give me a particular disease, and it will be either cured or prevented. But that's not the same thing.)

But What If The Information Isn't There?

The existence of at least one way to put people into stasis has one more consequence. We can say that a condition is incurable (meaning permanently incurable, not just incurable by present technology) if the information is permanently lost. Without any means to put patients in stasis, doctors must decide what is curable and incurable in a hasty fashion. Nobody can afford to wait. But with cryonic suspension, there is no hurry at all. We simply don't have to decide that someone is gone until we have full and complete understanding of what happened to them. Before cryonics, the patient was assumed dead unless proven otherwise; after cryonics, we assume that the patient is alive unless proven otherwise.

To prove that someone is gone must necessarily take a long time. This is the point where we have to make our peace with the unknown. The key fact is that we have barely begun to study this subject. We have only a few micrographs, with a small number of stains. We lack biochemical data. We lack many more studies, using many more stains. For instance, osmium tetroxide is a common stain for electron microscopy. This chemical binds to lipids in cell membranes. If it isn't present in a cell region, this should tell us that the cell membranes have missing lipids. Are these all lipids, or only particular lipids? Are there other structures which remain? We lack a knowledge of the chemistry/physiology of this degradation. Even following a dog brain at intervals of (say) 15 minutes, watching the structures change, would tell us a lot about what's happening. In fact, even for this ONE pathological condition of prolonged ischemia getting a complete account of what happened would take lifetimes of scientific work.

About 10 years ago I looked through the literature with neural archaeology in mind. I wrote up some of what I found in my bibliography (A Brief Scientific Introduction to Cryonics). This bibliography is of course very out of date. But there is one thing I never said much about in it, and that fact is fundamental to what we are now doing. The truth is, every single paper I quoted was written with some other aim in mind. Nobody was seriously trying to study the physiology of ischemia at 2 hours. These authors hadn't imagined the idea of studying that. In fact, they'd all probably react with outrage to someone quoting them as I did. They were always interested in something else, and the information I wanted just fell out. It is reported that DNA is recoverable from brains at 2 hours warm ischemia. We need studies of DNA in brains. There are stains for DNA we might use. It is also reported that lysosomal enzymes don't actually play a large role in events during warm ischemia. A fascinating fact, if true. There are known stains to localize these enzymes. Who has done this work? Who will do this work, other than cryonicists?

But the question with which I began this section contains much more than just an expression of doubt. Right now, we don't know enough to say. But it is certain that if we never look for remains of memory in these brains, we'll never ever find them. We've barely begun to look.

It's in the dynamic of cryonics that every patient stored will come back in some form. Why not? If you have spent 300 years to clarify this patient's problem, it would be senseless to just throw them away.

There are two special objections to neural archaeology deserving of an answer.

• 1. Brain cells are on such a small scale compared to archeological objects that the available room for the same kind of special inference is too small.

This statement presupposes that the only kind of archaeological inference possible consists of examining the parts of the fragments we find. For instance, archaeologists might look at fragments of wood, and date them using radiocarbon dating techniques. However, archeology does not only look at parts of parts. The first thing done in examining an archeological site is to carefully plot the relation of all the fragments to one another. Debris has a structure too. We discover this structure by looking at the relations of its parts to one another, not just by looking at the parts. (Archaeologists in Central America complain constantly that valuable artifacts are taken away and sold, with no record of where they were found, in relation to what). If a protein has two degradation parts, we can learn a lot by knowing where these parts are found in the remains of a cell.

In fact, one way of looking at cryonics is that it is simply a way of making such a detailed record. Here is a patient's brain, in the condition it was when we lost him.

Furthermore, it's not clear or obvious that we can't examine some of the parts. Decomposition products of brain chemicals can be specific indicators that they were there. Enough DNA fragments can tell us an entire genome. Proteins and polypeptides in nerve cells can be 10,000 to 100,000 daltons molecular weight or more. Even if fragmented, the fragments can give us much information.

• 2. If we make such a reconstruction of a patient from debris, will the patient be the same person?

This question, of course, is the question about identity (or the soul) with which every committed cryonicist is obsessed. It is right to be obsessed. It is fascinating to watch, because the fact that we are obsessed by it tells us about the future of humanity. When we take over, no joke, the newspapers will have pages devoted to the problem of identity every day of the week. (No longer aging now, but instead identity! ) As for answering the question, I don't know. We can do this to animals, and if they pass all tests we'll say they have come back. But animals, of course, aren't aware (?) or at least can't tell us so. It seems to me a fundamentally unknowable question, akin to asking if someone else has self-awareness.

But some things can be said. For instance, if memory is stored in proteins, and if these undergo constant turnover, then exactly what is the difference between this renewal process and recovery of memories from protein fragments? Your memories wouldn't even be the same molecules from day to day. Some patients have ischemic episodes from which they recover. During these they show fleeting symptoms exactly like those of stroke patients (if this happens to you, see your doctor immediately. You may soon have a real stroke, and something can be done about it before it happens). No such patient has ever claimed that they were fundamentally different while this went on. It is not easy to draw any lines here. It will become far less easy in the future.

If we take seriously the proposal that our souls are patterns of organization, then it must follow that these souls are recovered when we do this archaeology. Isn't the pattern of organization recovered? I cannot think of any experimental difference between the notion that I would be the same person after recovery and the notion that I am the same person as I was when I was 8 years old.

The Unknown As A Fundamental Problem

But there is a fundamental practical problem, not to neural archaeology but to the issue of knowledge. I've just argued that only cryonicists would even think of doing the kind of studies we'd need. This comes down to making peace with the unknown. You see, even cryonicists aren't going to get any answers for a long time on any of these death pathologies. And when we do finally get answers for some of them, we'll discover many others we haven't even imagined. We won't just find out about ischemia. We're much more likely to discover many new varieties of ischemia, some of which we understand and others we do not.

It's obvious what is happening. Medical conditions aren't all studied with equal intensity. We don't notice the same amounts of money going into cystic fibrosis research as into cancer. As societies we rank these conditions according to how immediately pressing they are. We then work on them in proportion. This must therefore mean that we will always have a vast number of medical problems for which study has hardly even begun. "Death" isn't really unique here. It's a commonplace that we know of many more diseases now than 100 years ago. Heart disease is now intensively studied, while in 1886 it received little attention. If a medical condition is unstudied, we can't be surprised that very little is known about it.

It is exactly these as yet unstudied problems for which cryonic suspension is intended. When thousands of scientists and doctors work in their laboratories to find a vaccine for polio, we know that the vaccine is imminent. It won't be hard to convince anybody that help is coming. Why would so many work on the problem unless they expected imminent success? Why should one lone scientist work on something else, when he knows that his own unaided efforts will make little progress with the problem? It is under exactly these conditions, when everyone agrees that success is imminent, that cryonic suspension will soon become useless. Cures will be found and the problem will vanish overnight. Yet a vast number of unstudied problems will remain, all summed up in a few words: death, fits, ague. Once there was only "cancer", until we studied it and found a thousand kinds, all different.

More than most, cryonicists believe that problems can have a technical solution. But that is simply not the belief of most people. Among cryonicists, even many longtime cryonicists who I feel should know better, there is an easy assumption that provable suspension and revival of brains will solve our problem. I believe strongly that work to suspend brains should be pursued. But I will also say that mere technical problems aren't really the key issue. If you want to be suspended, you'll have to make your peace with the unknown. The problem is that to all of those people out there, it is not obvious that aging will be curable. It is not obvious that their diseases will ever find solution. It is not obvious that we can raise the dead.

You think that all we have to do is to convince people that we can freeze and store them. But they believe that all their problems are fundamental aspects of human existence. What a pointless procedure to take a dying man and plunge him 200 years into the future so that he can die there! What fantastic nonsense, that the human life cycle will ever change! What we have to do to make cryonics spread is to change public attitudes to the unknown. That's much harder to do that just to prove suspension of brains. And it's the unknown for which cryonics is intended. If we knew how to cure this man's problem, we would not freeze him in the first place. And the unknown always dances just one step ahead of us, always out of reach.

What Do We Do Now?

We have many pressing problems. Current dog experiments at Cryovita and elsewhere focus rightly on the most probable case. That is one in which we capture the patient in a hospital, apply CPR or even ECMO, and therefore both cool and oxygenate their brains. The ischemia experiments don't even apply to this case. But even for this case they provide a baseline. We can think about doing a similar series for dogs treated parallel to the way human hospital patients are treated. This would give us valuable feedback about our procedures. Furthermore, it's not quite the same as current dog experiments, which involve rapid cardiopulmonary support rather than HLR treatment with drugs. We need more work like the recent Cryovita model of no oxygenation, to find drug regimens which will better protect patients treated in this likely way.

Unfortunately money and time are very short. However, I believe that we should continue the ischemia experiments too, although with lesser priority. My reason is that all members face a significant risk of freezing in poor conditions. The risk of autopsy alone is enough to merit work on ischemia. What we need is much more work to define what is happening to ischemic brains. For light microscopy, we need a greater variety of histochemical stains. We need work done at smaller intervals, particularly in the earlier stages of ischemia. We need attempts at cell culture, to bound (for instance) the times at which isolated brain cells can recover (The no-reflow phenomenon, and all the difficulties in restoring circulation, won't play any role in recovering isolated cells. It seems to be an assumption that brain cells won't survive. This is not an experimental fact). We need to correlate electron-microscopic stains with their chemical affinities and work out a historical account of what has happened to these cells.

What will come of such a study? I don't know. But then, this article is about making peace with the unknown. There are very few references for our question. We have to provide them for ourselves. It's called pioneering, which is exactly about making peace with the unknown.