Fight Aging!

In a recent published article a neurobiologist focused on the study of nematodes calls cryonics "impossible." He declares that the data of the mind is not being preserved and that people who are cryopreserved today cannot be restored. This is followed by another article in which a neuroscientist focused on brain mapping tells the former author that he is full of it and out of touch. It should be noted that the second fellow in this exchange doesn't think all that much of the cryonics industry as it is presently constituted, and favors the as yet commercially unavailable approach of plastination; there are always more than two sides in any argument.

Cryonics is the indefinite low-temperature storage of the brain as soon as possible following clinical death, and the small industry that has carried out this procedure since the 1970s has been in the news of late. The objective is to preserve the fine structure of neural tissue and nerve cell connections that encode the data of the mind. Provided that is stored successfully, then foreseeable forms of technology will in the future enable restoration and repair of this tissue. Early cryonics involved straight freezing, which wrecks tissue due to ice crystal formation. Modern cryonics aims for as-complete-as-possible vitrification via cryoprotectants, a process that suppresses ice crystal formation. There is ample evidence based on present theories of neural data encoding to believe that the necessary information is being preserved, albeit not the final absolute proof that many demand.

One has to be cautious of ascribing too much weight to the discussions of scientists who step beyond their fields; expertise in one area doesn't translate to the pronouncement of scripture for all areas. Indeed, if the error rates of scientific papers are anything to go by, one should think that a scientist's expertise enables them to be reasonably correct in their own specialty about half the time, and that after the expenditure of a great deal of work, collaboration, thought, and error-checking. Advancing the front lines of science is a challenging endeavor. For the purposes of the two articles I'll point out here, attacking and defending the scientific basis for cryonics, the boundaries of specialty and knowledge are such that a neurobiologist doesn't necessarily have the expertise in cryobiology to offer a fully informed opinion on the overlap between those two fields. The neurobiologist doesn't necessarily have the experience in the relevant areas of neurobiology for that matter - it is a very broad field with many deep and narrow specialties.

Anyone with a logical and inquisitive mind can make reasoned arguments, and those arguments are often worthy of engagement, but they should be taken for what they are. My objection here is not the matter of expertise, but the incoherence of the argument made against cryonics. Personally I'm all for arguing against mind uploading as the ultimate destination for cryopreserved individuals; it is possible and plausible, but a copy of you is not you, and only restoration of the original gives you continuity of existence. But if you are going to say that restoration of any sort is impossible then I expect to see a little more than "this is hard, the situation is complex, I don't see how it can be done, therefore it can't be done." At the very least I would expect the outline of a theory as to what it is that the method of preservation destroys. If you are not familiar with the current state of the intersection between cryobiology and neurobiology then fine, but don't write an article based on knowing something about that thin field of practice and theory without first stepping out into the unknown and learning what is going on and who is doing the cutting edge work. An intelligent individual can grasp the bones of a field close to his or her own specialty with a little study, and then say useful things, but that is not what is happening here.

The False Science of Cryonics

The cryonics industry offers to preserve people in liquid nitrogen immediately after death and store their bodies (or at least their heads) in hopes that they can be reanimated or digitally replicated in a technologically advanced future. Proponents have added a patina of scientific plausibility to this idea by citing the promise of new technologies in neuroscience, particularly recent work in "connectomics" - a field that maps the connections between neurons. The suggestion is that a detailed map of neural connections could be enough to restore a person's mind, memories, and personality by uploading it into a computer simulation.

I study a small roundworm, Caenorhabditis elegans, which is by far the best-described animal in all of biology. We know all of its genes and all of its cells (a little over 1,000). We know the identity and complete synaptic connectivity of its 302 neurons, and we have known it for 30 years. If we could "upload" or roughly simulate any brain, it should be that of C. elegans. Yet even with the full connectome in hand, a static model of this network of connections lacks most of the information necessary to simulate the mind of the worm. In short, brain activity cannot be inferred from synaptic neuroanatomy.

Synapses are the physical contacts between neurons where a special form of chemoelectric signaling - neurotransmission - occurs, and they come in many varieties. They are complex molecular machines made of thousands of proteins and specialized lipid structures. It is the precise molecular composition of synapses and the membranes they are embedded in that confers their properties. The presence or absence of a synapse, which is all that current connectomics methods tell us, suggests that a possible functional relationship between two neurons exists, but little or nothing about the nature of this relationship - precisely what you need to know to simulate it.

The features of your neurons (and other cells) and synapses that make you "you" are not generic. The vast array of subtle chemical modifications, states of gene regulation, and subcellular distributions of molecular complexes are all part of the dynamic flux of a living brain. These things are not details that average out in a large nervous system; rather, they are the very things that engrams (the physical constituents of memories) are made of. While it might be theoretically possible to preserve these features in dead tissue, that certainly is not happening now. The technology to do so, let alone the ability to read this information back out of such a specimen, does not yet exist even in principle. It is this purposeful conflation of what is theoretically conceivable with what is ever practically possible that exploits people's vulnerability.

No one who has experienced the disbelief of losing a loved one can help but sympathize with someone who pays $80,000 to freeze their brain. But reanimation or simulation is an abjectly false hope that is beyond the promise of technology and is certainly impossible with the frozen, dead tissue offered by the "cryonics" industry. Those who profit from this hope deserve our anger and contempt.

Ken Hayworth's Personal Response

As a neuroscientist I feel compelled to rebut some of your points. First off, please do not conflate what a small, highly-suspect company like Alcor is offering with what is possible in principle if the scientific and medical community were to start research in earnest. I started the Brain Preservation Prize as a challenge to Alcor and other such companies to 'put up or shut up', challenging them to show that their methods preserve the synaptic circuitry of the brain. After five years they have been unable to meet our prize requirements even when their methods were tested (by a third party) under ideal laboratory conditions. Out of respect for loved ones I will not comment on any particular case, but it is clear from online case reports that their actual results are often far worse than the laboratory prepared tissue we imaged. Speaking personally, I wish that all such companies would stop offering services until, at a minimum, they demonstrate in an animal model that their methods and procedures are effective at preserving ultrastructure across the entire brain. By offering unproven brain preservation methods for a fee they are effectively making it impossible for mainstream scientists to engage in civil discussion on the topic.

Unlike you however, I do think that cryonics and other brain preservation methods are worthy of serious scientific research today. First off, the cryobiology research laboratory 21st Century Medicine has published papers showing that half millimeter thick rat and rabbit hippocampal slices can be loaded with cryoprotectant, vitrified solid at -130 degrees C, stored for months, rewarmed, washed free of cryoprotectant, and still show electrophysiological viability and long term synaptic potentiation. They have so far been unable to demonstrate such results for an intact rodent brain - unlike the in vitro slice preparation, perfusing the cryoprotectant through the brain's vasculature results in osmotic dehydration of the tissue.

However, this same research group now has a paper in press showing that such osmotic dehydration can be avoided if the brain's vasculature is perfused with glutaraldehyde prior to cryoprotectant solution. Their paper reports high quality ultrastructure preservation across whole intact rabbit and pig brains even after being stored below -130 degrees C. I have personally acquired 10x10x10nm resolution FIB-SEM stacks from regions of these "Aldehyde Stabilized Cryopreserved" brains and have verified traceability of the neuronal processes and crispness of synaptic details. Considering these two results together, it seems at least plausible that further research might uncover a way to avoid osmotic dehydration without the need to resort to fixative perfusion, resulting in an intact brain as well preserved as the viable hippocampal slices. Even if glutaraldehyde remains a necessity, this Aldehyde Stabilized Cryopreservation process appears capable of preserving the structural details of synaptic connectivity (the connectome) of an entire large mammalian brain in a state (vitrified solid at -130 degrees C) that could last unchanged for centuries.

You state: "The presence or absence of a synapse, which is all that current connectomics methods tell us, suggests that a possible functional relationship between two neurons exists, but little or nothing about the nature of this relationship--precisely what you need to know to simulate it." Really? Little or nothing is known about the nature of the photoreceptor to bipolar cell synapse in the mammalian retina? Little or nothing is known about the bipolar to ganglion cell synapses? We may not know everything about these retinal cells and synapses but we know enough to have had "simulations" of retinas for two decades. Not based on the EM-level connectome directly but based on the statistics of connectivity as gleaned from coarser mappings. Do you really suspect that we would not be able to tell whether a particular retinal ganglion cell has an on-center or off-center receptive field based on the EM-level connectome alone? The textbooks and recent retinal connectomic studies argue otherwise.

I am certainly not saying that we now know everything about how the brain works, but I am saying that there is more than enough reason to suspect that the structural connectome may be sufficient to successfully simulate a brain given the depth of neuroscience knowledge we should possess by the year 2100 or 2200. Dismissing that as even a possibility hundreds of years in the future based on your failed attempts at understanding some particulars of C. elegans nervous system today seems very shortsighted. If you have real theoretical arguments then present them.

I personally agree, no one should pay $80,000 to freeze their brain without solid, open, scientifically rigorous evidence that at the very least the connectome is preserved. I would go further and say that regulated medical doctors are the only ones that should be allowed to perform such a procedure. But I do not agree that research in this area is doomed to failure. Instead the scientific and medical communities should embrace such research following up on the promising brain preservation results I mentioned above. Scientists should work to perfect ever better methods of brain preservation in animal models, and medical researchers should take these protocols and develop them into robust surgical procedures suitable for human patients.

I should say that Alcor under the leadership of Max More is open about how they preserve tissues, the present limitations and unknowns of the process, and the directions they are taking to improve the practice of cryopreservation under conditions of limited funding. Take a look through their extensive documentation and case studies presented at their website. I think it is far from fair to call that organization suspect. The perfect is the enemy of the good, and improvement in cryonics absolutely requires a practicing industry to drive that change. Within that framework, all challenges to prove effectiveness and improve towards an ideal are good and very welcome. This field, like all others related to preservation of life, is in great need of more funding, more support, and faster progress.