Tag: Chemical Fixation

Ken Hayworth on straight freezing in cryonics

Ken Hayworth’s idea of promoting a fixation-based alternative to brain cryopreservation is something I am highly sympathetic to overall, and I hope some progress in this direction results from the work he is doing and trying to induce others to do. That said, I wanted to comment on Hayworth’s remarks about straight freezing of brain tissue.

Figure 1B shows the horrific damage (destroyed cells) that occurs when such a slice is “preserved” using a freezing technique typical of those employed early in cryonics. Such damage is clearly irreversible by any future technology and it should come as no surprise that such techniques were flatly rejected by the scientific and medical community.

While it’s true that straight-frozen tissue as shown looks pretty awful I think it’s too strong a statement to say that “such damage is clearly irreversible by any future technology” unless you have further supporting arguments. To invoke a relevant analogy, we could run a phone book through a garden-variety shredder found in many offices, and still be able to reconstruct it from the resulting debris. The fact that there is debris remaining with the frozen tissue (as opposed to the cases of decay or burning) means we cannot, without further argument, rule out some sort of reconstructive process using future technology, including nanotechnology. It is also worth noting that with imperfect chemical fixation you run a risk of tissue loss over time that does not occur with cryopreservation; even debris resulting from straight freezing will remain as-is so long as cryogenic temperatures are maintained.

I also note that Hayworth says his proposed plastination could only be done properly if you start with a living patient with still-beating heart to distribute the initial fixative.

It is important to understand that the standard fixation and plasticization protocol is started while the animal is still alive. If the animal’s heart is allowed to stop for even a few minutes before the glutaraldehyde is perfused into the vasculature, then the quality of the preservation is markedly reduced. This fact will also be true for any whole brain protocol based on perfusion.

This of course would be problematic for any procedure to be used on humans; you’d have to treat it as some form of euthanasia.

Chemical preservation and cryonics research

In the 2009-4 issue of Alcor’s Cryonics magazine I review the technical and practical feasibility of chemical preservation. One of the most interesting aspects of chemopreservation is that it could play a useful role in the cryopreservation of ischemic patients.

There is accumulating evidence that it is a lot more difficult to prevent ice formation in patients with extensive ischemic injury. This raises the question whether some cryonics patients could benefit from chemical fixation prior to transport and cryoprotective perfusion.

Such protocols raise a number of obvious concerns but the question is not so much whether these procedures are inferior to vitrification of non-ischemic patients, but whether fixatives can improve the situation of some ischemic patients compared to the prospect of substantial ice formation, or even straight freezing (cooling without cryoprotection). This is an empirical question which needs to be settled by experimental research.

Chemopreservation: The Good, The Bad and the Ugly

Brain preservation

Mind uploading advocate Kenneth Hayworth has launched an interesting website devoted to the science of brain preservation. Of particular interest is his Proposal for a Brain Preservation Technology Prize (PDF). This document includes one of the most comprehensive discussions of chemopreservation as a strategy for personal survival. For example, one of the most common objections to chemopreservation is that fixatives like formaldehyde and glutaraldehyde do a poor job of fixing lipids. In this document, Hayworth reviews a number of papers where a fixative that can stabilize lipids, osmium tetroxide, is perfused (!) through the circulatory system.   For human sized brains such a step would be necessary to avoid the ischemic damage and autolysis that would occur in the case of the time-consuming alternative of diffusion fixation.  He also speculates that such a fixed brain can be perfused with a high viscosity plastic resin for long term preservation.

One of the limitations of this approach, as the author concedes, is that the procedure needs to be started before death. In reality, the situation is even more challenging  than that because the procedure would have to be started before ischemia-induced brain perfusion abnormalities associated with terminal disease and the agonal phase will manifest themselves. This is a problem where “old fashioned” cryonics has a clear advantage. Perfusion impairment may interfere with complete distribution and equilibration of the cryoprotectant in the brain but the unperfused tissues will still be stabilized (although in a damaged form) through low temperatures. In the case of chemical fixation such a “second chance” is absent. This is not just a theoretical problem. Cryonics researchers have become painfully aware of the adverse effects of even the slightest perfusion artifacts on the quality of fixation and the resulting electron micrographs.

As a consequence, this kind of “high quality” chemopreservation can only be a credible alternative for cryonics if the medical establishment would permit the procedure for those who are diagnosed as terminally ill. If the acceptance of cryonics is any guidance, there is little chance that this will happen any time soon.

Chemopreservation has another major obstacle to deal with. As the cryobiologist Brain Wowk has stated on numerous occasions, chemical fixation is a dead end in terms of reversibility with contemporary technologies. This aspect of chemical fixation limits the demonstration of its technical feasibility to a demonstration of ultrastructural preservation.  In the case of cryonics, evidence of excellent ultrastructural preservation has produced little excitement among the scientific establishment and the general public. Linking chemopreservation exclusively to mind uploading may present another obstacle to its acceptance.

In his essay Killed by Bad Philosophy: Why brain preservation followed by mind uploading is a cure for death [PDF] Kenneth Hayworth attempts a defense of mind uploading by identifying the philosophical errors that those who reject the concept, and those who argue that “a copy is not you” in particular, engage in. The author shows little doubt about his position although one might object that the central example that is used to make the case could also be used to  argue against mind uploading. One might even object  that the whole debate involves a pseudo-problem if any kind of empirical observation can be made consistent with the case for and the case against mind uploading.

Aside from these complexities, this is an admirable effort to raises interest in high quality brain fixation. Initial funding for more experimental research should be encouraged.

Albert Einstein's brain and information-theoretic death

“People like you and I, though mortal of course like everyone else, do not grow old no matter how long we live…[We] never cease to stand like curious children before the great mystery into which we were born.”

Albert Einstein

One sign of the lack of faith in the future progress of technology and the poor acceptance of the neurological basis for mind is the way in which our society treats the “post-mortem” human brain.

In some cases, the brains of those whom modern medicine cannot help are removed after cardiopulmonary arrest and donated (by the permission of the patient or the family) for research. In such cases, the brains are preserved so they can be studied over a long period of time. They are also sectioned and prepared in other ways for examination. Such donated brains have helped scientists learn about the human brain, with an eye to improving methods for treating conditions such as Alzheimer’s or mental illness. However, other brains have been preserved mainly because they belonged to famous people.

One of the more famous cases is the brain of Albert Einstein, removed in 1955 and preserved apparently without his or his family’s permission, and then made available for study. According to an NPR report, Einstein’s brain was fixed, sectioned into over 200 blocks, embedded in celloidin, and then stored in formalin.

Since that time, Einstein’s brain has been further sectioned and divided among researchers. A 1985 study by Diamond et al. reported that the Einstein brain sections’ neurons were still observable, and the study’s authors even assumed the number of neurons preserved in Einstein’s brain would be the same as those in recent preserved brains.

Presumably, people have wanted to study the brains of famous people in order to learn something about what made those people special. Turning a person into a mere object of study is a questionable notion, though, and the idea that the study could yield any information about the person’s mind underscores how it is widely accepted by scientists that the brain instantiates the mind, and thus the person.

Neuroscience is still too much in its infancy to make much sense of the evidence of the brain, as the scientific reception to the Diamond study showed. We do not yet know how to “read” the brain for the specific memories and personality traits and other phenomena of mind stored in it. However, because we do know enough now to know that the mind arises from the brain, we must realize that to preserve the brain is to preserve the potential of mind, and to preserve the potential of mind is to preserve the possibility of life for the person whose brain it was.

The neural basis of personhood sits ill with older notions such as immaterial souls or spirits. The neural basis of personhood also fits poorly with existing medical and public policies such as commonly accepted definitions of death and laws related to end of life. If death is understood as irreversible damage to certain identity-critical areas of the brain, the irreversibility of such damage is put into question by every advance in the treatment of injury and disease of the brain, as well as by the brain’s mysterious ability to recover from conditions such as minimally conscious state after many years. The cardiopulmonary-arrest definition of death does not involve the condition of the brain, and the usual definitions of brain-death do not distinguish between identity-critical areas or aspects of the brain and other areas or aspects of the brain. A more rigorous definition of personal death has been developed by Ralph Merkle, who states:

“A person is dead according to the information-theoretic criterion if their memories, personality, hopes, dreams, etc. have been destroyed in the information-theoretic sense. That is, if the structures in the brain that encode memory and personality have been so disrupted that it is no longer possible in principle to restore them to an appropriate functional state then the person is dead. If the structures that encode memory and personality are sufficiently intact that inference of the memory and personality are feasible in principle, and therefore restoration to an appropriate functional state is likewise feasible in principle, then the person is not dead.”

Although there is still some lack of clarity about the “etc.” and “appropriate functional state”, this definition of death at least is founded on the neural basis of personhood. Those who believe in the future progress of technology and accept the neural basis of personhood are led inevitably to understand that preserving the brain is preserving the person, potentially for later resuscitation.

It is not impossible to imagine that, in a more advanced future time, the formalin-fixed, celloidin-embedded brain sections could be reassambled, and if the synaptic circuitry of the neurons were well preserved, any significant damage could be repaired. The brain might be able to be returned to a viable state by reversal of the fixation and removal of the celloidin embedding. Resuscitation of an isolated brain would be unacceptable, but eventually it might be possible to restore the rest of the body around the brain by cloning or regeneration of the cells or some other prosthetic embodiment.

As amazing as it may seem, a patient reduced to a preserved brain, whose mind would be in a stopped state, might be able to be healed, that is, totally restored to a healthy body and a mind which could resume the life it left off, with all the memories and personality intact.

The case of Albert Einstein’s brain is unfortunate. All the impudent cutting, handing around, and tampering with Einstein’s brains sections, and the crude preservation method, may have irreversibly damaged the neural basis of his personhood. Yet we do not know enough today about the brain to know how much of it needs to be preserved, and in what state, to be able to revive a person with future technology. The preservation of the brain, though, would provide a theoretical possibility of future resuscitation. It may not be possible to someday restore Albert Einstein from the remains of his brain, but if it were possible, those in possession of the brain sections would first have to be willing to consider whether their “specimens” might be the restorable fragments of a still potentially living person who deserves to live more than to be studied.

Warm biostasis through nanotechnology

One concern about chemical fixation as a low cost alternative to cryonics is that current fixatives may not be able to permanently fix all biomolecules that are important to preserve the identity of the person. A related concern is that postmortem delays may not permit adequate perfusion of the brain, resulting in pockets of decomposed tissue. On this issue, biostasis at cryogenic temperatures (cryonics) has a distinct advantage because extreme cold will also preserve tissues that were not, or were poorly, penetrated by the cryoprotectant agent.

But even if cryoprotectant toxicity will be overcome to enable reversible vitrification of humans, the procedures of cryoprotectant perfusion, cryogenic cooldown, long term care, rewarming, and resuscitation may often involve (unintended) imperfections that will require advanced cell repair technologies for successful resuscitation.

Perhaps those same advanced technologies could produce a form of biostasis that avoids the crude consequences of contemporary chemical fixation by making precise modifications within and between cells to arrest metabolism and decomposition.

Looking for discussion of this idea, Brian Wowk pointed this writer to Eric Drexler who envisioned such a form of warm biostasis in Engines of Creation. In chapter 7 (section 5) Drexler calls this form of warm biostasis “anesthesia plus:”

To see how one approach would work, imagine that the blood stream carries simple molecular devices to tissues, where they enter the cells. There they block the molecular machinery of metabolism – in the brain and elsewhere – and tie structures together with stabilizing cross-links. Other molecular devices then move in, displacing water and packing themselves solidly around the molecules of the cell. These steps stop metabolism and preserve cell structures.

This procedure would produce a state in which the person will appear to be dead (and warm) for all practical purposes:

If a patient in this condition were turned over to a present-day physician ignorant of the capabilities of cell repair machines, the consequences would likely be grim. Seeing no signs of life, the physician would likely conclude that the patient was dead, and then would make this judgment a reality by “prescribing” an autopsy, followed by burial or burning.

Such a form of warm biostasis would not only produce a true molecular alternative to cryonics, it would also enable long-duration space travel and could be employed as a means to provide trauma care in emergency situations. These kind of applications of molecular nanotechnology are extremely advanced and, as a result, literature, either fiction or non-fiction, about them is virtually non-existent. It seems that the first rigorous treatment of cellular and whole-body warm biostasis will be published in Robert Freitas’ Nanomedicine Volume IIB and Nanomedicine Volume III (personal correspondence).

Perhaps the future of biostasis will be an advanced form of chemical fixation after all.