This is my rebuttal to the recent MIT Technology Review article by Michael Hendricks. The views expressed here are mine alone and should not be taken as an official statement from the BPF which is an organization with a diverse range of opinions but a common goal to advocate more scientific research into brain preservation…

Dear Michael,

As a neuroscientist who was heavily quoted in the NYT article 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. Since it was invented in the 1960’s, the argument against cryonics has been that it (to quote the skeptic Michael Shermer) turns your brain to “mush”. This was certainly the case in the 1960’s but I wondered whether it was still the case fifty years later so I put forward my skeptical challenge not only to the cryonics community but to the scientific community as well, and I consider the results encouraging so far.

First off, the cryobiology research laboratory 21^st Century Medicine has published papers (1, 2) 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. Shawn Mikula, another researcher competing for the brain preservation prize, has demonstrated a method for staining an entire intact mouse brain allowing it to be imaged at high resolution with 3D electron microscopy, and other researchers have begun to show how to perform such imaging in parallel, dividing the brain up into pieces and imaging the individual pieces with ultrafast 61 beam scanning electron microscopes.

To summarize, it looks like as of 2015 we may finally have a method (Aldehyde Stabilized Cryopreservation) that can demonstrably preserve the synaptic connectivity of a brain over centuries of storage. This should at least put the “mush” argument to rest. And we are beginning to see a plausible path for how such a brain’s connectome might be mapped in the future. So at the very least, the question of whether a connectome map is sufficient to “restore a person’s mind, memories, and personality by uploading it into a computer simulation” is no longer purely academic.

So let’s dive in…

You state: “Science tells us that a map of connections is not sufficient to simulate, let alone replicate, a nervous system…”

Really? Science tells you this is “impossible” because you have failed to do so in your worm studies so far?

You state: “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.”

This is incredibly misleading. The reason that the nervous system of C. elegans is difficult to ‘simulate’ today is that not enough is known about the functional properties of its neuronal types and synapses. The argument for future uploading assumes such knowledge will be completely known from decades of ‘side’ experiments. Are you saying that even if every detail of electrophysiology were known for the general C. elegans that one could still not interpret the structural connectome of a particular C. elegans to determine if it has or has not learned an olfactory avoidance task? Even if you suspect this, where is your evidence?

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.

Is little or nothing known about the synapses made by thalamic projections to the visual cortex? About the synapses made by spiny stellate cells and pyramidal cells in cortex? Textbooks say these are all glutamatergic and excitatory. Do you really suspect that it would be impossible, in principle, to determine the receptive field orientation of a cortical simple cell if you had a complete connectome? If you do you should tell the researchers at the Allen Institute since they are planning to do just that.

But maybe you say a simulation is more than just determining receptive fields. The success of deep learning convolutional neural networks argues against this. In a sense these neural networks are “simulations” of the visual cortex and they are very successful now at learning to recognize objects. These neural networks show directly how complex information can be encoded in a connectome, one receptive field at a time. If I took a Google deep learning network and read off its connection weights I could “copy” and “upload” it to another neural network simulation even if the individual connections strengths were determined only imprecisely. The textbooks say similar hierarchical networks of feature detecting cells underlie our own visual system.

By the way, you certainly get more than the “presence or absence of a synapse” from modern EM reconstructions. Check out this paper to see just how much information on synapse strength can be gleaned from 3D EM images alone.

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.

You state: “Finally, would an upload really be you? …But what is this replica? Is it subjectively “you” or is it a new, separate being? The idea that you can be conscious in two places at the same time defies our intuition. Parsimony suggests that replication will result in two different conscious entities. Simulation, if it were to occur, would result in a new person who is like you but whose conscious experience you don’t have access to.”

It always boggles my mind that smart people continue to fall into this philosophical trap. If we were discussing copying the software and memory of one robot (say R2D2) and putting it into a new robot body would we be philosophically concerned about whether it was the ‘same’ robot? Of course not, just as we don’t worry about copying our data and programs from an old laptop to a new one. If we have two laptops with the same data and software do we ask if one can ‘magically’ access the other’s RAM? Of course not.

We are evolved biological robots, period. That is what science really has told us unequivocally. Do you seriously disagree with this? There are no magic molecules in the brain that define us, just computation. Our consciousness is just another type of computation, one that computes a ‘self model’ to assist in intelligently planning our future actions. Such computationalism is the foundational assumption of cognitive science and I would argue of neuroscience as well. There is no room for magic in neuroscience.

You and an exact copy of you wake up in separate but identical rooms. One of the rooms is chosen at random to be blown up. You are saying there is a critical difference whether it is the copy’s room or the original’s. By assumption, this situation is perfectly symmetric from a materialist perspective yet you cling to the idea that there is an overwhelming fundamental difference.

When I hear a neuroscientist making this “identical copy” argument it is like hearing an evolutionary biologist saying that they believe all other animals evolved by natural selection, just not humans. It is like Galileo telling the Inquisition that the planets do revolve around the sun, but don’t worry, we all know that God is the one pushing them.

Seriously, if you are a neuroscientist you need to drop the ‘vitalism’ nonsense. If you want to say that uploading will take more than the structural connectome then say specifically what it will take. But to say uploading is impossible in principle because of this ‘copy problem’ intuition is to turn your back on the computational theory of mind in general.

Finally you state: “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.”

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. Regulators should enforce the highest quality standards for such procedures to be performed by licensed professionals in hospitals. And laws should be changed to allow terminal patients like Kim to take advantage of them prior to cardiac arrest (avoiding weeks of self-starvation and dehydration).

Kim’s story is tragic at least in part because the scientific and medical community let her down. She was a neuroscientist, and one that fully embraced the computational theory of mind. She knew what she wanted -a high quality brain preservation prior to death. I am a neuroscientist that wants the same thing, and there are others. Who are you to say that we are wrong in our beliefs? Who are you to say that the hard-won progress that has already been made toward medical brain preservation should be abandoned?

 

-Kenneth Hayworth (The opinions expressed here are mine alone.)