This essay was submitted to Open Philanthropy’s Cause Exploration Prizes contest.

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tl;dr

Nothing OpenPhil or in fact anything anyone has ever done has truly “saved” anyone’s life. Regardless of what we do, everyone still dies eventually. And almost every death happens at a time and in a manner that is not of the dying person’s choosing. Truly saving someone’s life would mean causing them to be in a state where they can live as long as they want, free of coercion. The brutal fact is that so far, we’ve only ever managed to delay the inevitable.

There is a vast scientific case to be made for preservation of people via aldehyde fixation and vitrification. Our current dominant theory of neuroscience, the synaptic basis of memory, says that preservation works. Even our less popular fringe theories of neuroscience say that preservation works. Preservation of human memory engrams via aldehyde fixation is a direct logical consequence of our current theories of neuroscience and information theory. Suggesting that preservation via chemical fixation does not work is logically equivalent to proposing a new memory system with exotic, biologically implausible elements and with no supporting evidence. Either preservation, done correctly, is sufficient to capture the essence of a person, or else the most basic foundations of the fields of neuroscience and biochemistry are catastrophically wrong, to the point of being literally fraudulent.

We can and should implement a broad program of engram preservation today, and it’s possible for OpenPhilanthropy to make major strides in this area. A true option of preservation, made broadly accessible, will likely have profound secondary effects for society as a whole. If people feel that they truly have a place in the future, they are more likely to plan for that future. If people have a practical solution for dealing with their own death, they will be able to think intelligently about their own death without as many psychological blocks. And if people can think about their own death more coherently, then they are likely to also think about other scary future possibilities in a more sober manner.

Preservation can be implemented cheaply and become the standard way we deal with death as a responsible society, and there is not much more work to be done to achieve a robust preservation program in as soon as five years. The limiting factors are funding, establishing common knowledge among disparate scientific fields, and political will.

We’ve never actually saved anyone’s life.

The point of philanthropy, and in fact the point of most human endeavors, is to enable human flourishing. We enable human flourishing in many ways, such as by increasing our capabilities through technology, or by decreasing coercion whether natural or man-made.

And the most central thing to human flourishing, and indeed the flourishing of any organism, is life itself. As long as you are alive, you have a chance to improve your condition and help others. You can move freely in the world, and learn, and potentially find happiness. But as soon as you are dead, your voice is silenced forever, and any chance of growth or improvement is permanently terminated.

Unfortunately, no intervention invented thus far has actually saved anyone’s life! At the end of the day, everyone still dies.

Truly saving someone’s life would involve transforming them from a state where they are definitely going to die, whether now or in 50 years, to a state where they can live as long as they like in good health. And unfortunately, none of the interventions we’ve thus far developed are up to the task.

It is better to think of the interventions available to us as simply delaying the inevitable. Cure cancer, for example, and you add about 5 QUALYs to everyone’s life, and then everyone still dies from other problems like cardiovascular disease. It’s a simple fact that almost everyone dies at a time and manner that they would not choose for themselves, Unwilling death is a grave injustice, perhaps the ultimate injustice of our age. Even the people who make use of end-of-life protocols to choose their time of death are not making a truly free, uncoerced choice, as the suffering associated with aging and terminal diseases is a natural form of coercion that prevents true consent. Take away the terminal disease and health problems, and they would likely not choose to end their life.

These are grim facts, but it is important to address them head on, because only by acknowledging the fact that we still don’t know how to truly save anyone’s life can we hope to soberly consider our options and work towards a true solution to the most profound injustice today.

Taking stock of our situation

It’s important to establish a few bits of common ground, a reasonable agreement on facts about the world, to discuss our options for improving our situation. The following points are the baseline on which to build the case that we can start saving people’s lives—for good—today.

1) There is no magical thing, unconnected from the physical world, which makes a person who they are. In this sense, materialism is broadly correct. Humans are extremely complicated, finite structures that obey the laws of physics. A person’s memories, skills, personality, and so on are physically encoded in their body and especially their brain.

Of course I do not deny that we humans are embedded in a greater family / society / ecosystem, and that the context in which we are embedded can dramatically change our attitudes and capabilities. Without an English-speaking society around me, or without my family, I am in some sense a different person. Nevertheless, you can draw a bright line around the physical border of a person’s body, specifying a certain collection of matter, and that matter will contain the colloquially-understood “essence” of the person, though that essence may need the right social context to be fully realized.

2) It is possible in principle to perform vast feats of engineering, especially if they’ve already been accomplished by nature. Specifically, I believe that it is possible for us to rise to the challenge and conquer the immensely complex task of “mind uploading”, which involves scanning an entire human body and simulating its internal causality in enough detail that the uploaded version will behave in all situations in the same manner that the pre-uploaded’s causality would dictate.

I do not for a moment want to undersell the vast complexity of mind uploading. The brain has a quadrillion synapses and it’s currently unknown what level of simulation detail is enough to make a reasonably faithful version of a person. Nevertheless, the technological components of mind uploading are clearly possible from an engineering perspective. Scanning a brain at nanoscale resolution, a likely prerequisite for mind uploading, would be possible within 10 years for a budget of around $1,000 billion, and there’s every reason to believe that that cost will continue to exponentially decrease, as it has for the last 40 years. Simulating a single neuron at a level of detail sufficient to recapitulate neuronal dynamics and learning is clearly possible in principle, because the neuron itself is built out of biomolecules which are themselves simulatable. Doing the same for 100 billion neurons is a matter of (monstrous) scale. The ultimate size/power requirements of a computer adequate for simulating a human, if we really know what we’re doing, should require no more than the size of a human body and no more energy than 2,000 Calories a day,, since each person is living proof that evolution has already achieved this engineering feat. If nature has already met the engineering challenge, then there is no reason in principle that we can’t eventually match or exceed what nature has already done.

3.) Preservation of a person is physically possible using today’s technology.

There is a vast scientific case to be made that preservation of a person is possible via aldehyde fixation and subsequent vitrification, which will not fit in this proposal. I’ve worked over the last several years to refine this technology, including winning the Large Mammal Brain Preservation Prize in 2016 and more recently running a human brain bank in the Pacific Northwest. The basic summary is:

Information Theory tells us what it means to preserve a complicated information-containing artifact using a preservation method, and that is that information-theoretically distinguishable initial states need to map onto distinct final states. Some examples:

Example: preserving books.

Say you want to preserve books. There’s more than one way to define a unique book. For example, you could count two different printings of the same title as the same book, if your criteria for a book was based on the same sequence of letters. Let’s look at a more stringent definition: a book is different from another book if their ink patterns are perceptually distinct according to a typical human observer paying careful attention. That is, a book with even a slight, smaller-than-a-letter difference that’s noticeable to the human eye—an ink smudge, a missing period—would be considered different than the same title without that ink smudge. Now, imagine pouring epoxy onto the book in order to preserve it. The epoxy works its way into every page, soaking the book through-and-through. And the epoxy glues the ink firmly to each page and the pages themselves to each other, before fully solidifying the book into a solid block of plastic. Does this method of preservation preserve books according to our criteria? Yes, because the epoxy does not move ink molecules enough to result in any confusion about which ink-pattern must have generated the resulting plastic block. Note that actually being able to open the book is not a requirement for a successful preservation; the resulting plastic book only needs be physically distinct from plastic blocks created from other ink patterns. Note also that we don’t need to be able to actually read the book; we don’t need to have good theories about the nature of literature; we don’t need to know how to write the book ourselves; we don’t need to be able to critique this book particularly or literature in general. In order to be confident that we’re preserving the book, we just have to understand how ink, paper, and epoxy works and have a reasonable understanding of which differences are perceptible to the human eye.

Example: preserving immune memory.

Consider immune memory, the body’s knowledge of self and other, a memory which is continuously updated throughout life in response to infection, vaccines, etc. Is aldehyde fixation sufficient to preserve immune memory? If we consider what meaningfully distinguishable immune memory states might be, a sensibly conservative starting point would be the capability of the immune system, taken as a whole, to generate different antibodies at different rates in response to stimuli such as infections. If two immune systems are able to make different antibodies, then they are different. Consider my own entire complement of antibodies and antibody-generation capabilities. This is some vast but ultimately finite set of distinct proteins. Now consider an exact copy of me, except that a single b-cell is modified so that it produces an antibody that differs from the previously produced antibody by a single amino acid. We can say that this subtle difference counts as the two immune systems being meaningfully distinct. Can aldehyde fixation preserve this subtle immune memory difference in an information-theoretic sense? Yes, because aldehyde fixation is capable of preserving every cell, and essentially all proteins, DNA, RNA, and other large biomolecules in an entire organism. Although the difference between these two example immune systems exists in only a single cell, the difference is actually quite large from a biomolecular perspective. That single amino acid difference is encoded in that cell in multiple places: in the DNA in the cell’s nucleus, in the RNA that is transcribed to construct antibodies, and in the final antibodies themselves. There are thousands of different molecules that meaningfully encode the difference between the two immune systems in that single cell, and aldehyde fixation is able to preserve essentially all of them. Therefore, aldehyde fixation is up to the task of preserving immune memory. Note that we don’t need a complete theory of immune memory—we don’t need to understand exactly how immune cells specialize to make different antibodies, for example—to be extremely confident that immune memory as we’ve defined it is preserved by aldehyde fixation in an information theoretic sense.

Example: preserving memory engrams

Similar to the above two examples, we must first define what it means for a complex information-containing system, in this case a person, to have “meaningfully different” engrams from another person. And then we must consider whether our preservation method will truly produce two different artifacts when starting with two similar, but different, beginning points. As a conservative starting point, we say that two people have “different” engrams if there is some stable difference in their behavior that persists over at least 24 hours. For example, consider two versions of me which are entirely identical, except that when I go to a party with a host I’ve never met, the host introduces herself to one version of me as Alice, and to the other version as Brittany. Twenty-four hours later, both versions of me still remember the name and will respond differently when asked who the host was.

What does neuroscience say would have to happen in these near-identical nervous systems to generate a stable behavioral change that lasts more than 24 hours? While we don’t have a complete theory of neuroscience, we know the low-level biochemistry of engram formation reasonably well and can definitively answer this question. Neuroscience says that hundreds to thousands of synapses would have to be different between the two nervous systems to reliably result in a different behavior. If those specific synapses were disrupted, then the behavioral difference would vanish. Now, what level of physical difference is aldehyde fixation able to preserve? Aldehyde fixation, competently performed, will not only preserve every single cell and synapse in the two nervous systems, but will also preserve essentially all proteins within each synapse. This means that aldehyde fixation is able to preserve such subtle differences between nervous systems that even two nervous systems that differed in protein content at a single synapse could in principle still be differentiated after preservation. Note that, like the two previous examples, we DO NOT need a complete theory of neuroscience to say with confidence that memory engrams can be preserved in an information theoretic sense. We just need to know enough about how the biochemistry of engram formation works to understand the magnitude of the changes that must happen in a brain to meaningfully encode a memory, and then compare that to the preservation capabilities of aldehyde fixation.

Next steps

Getting comfortable with these concepts

I’ve previously talked with OpenPhil about engram preservation and was told that it’s an interesting idea, but that OpenPhil doesn’t have the specialists to properly evaluate it. I suggest that for something as important as engram preservation that it’s worth it to actually evaluate it. I call on OpenPhil to consult with experts in information theory, biochemistry, neuroscience, and clinicians who perform deep hypothermic circulatory arrest or otherwise expose the nervous system to extreme states. Get these experts in a room together, and have a focused conversation about the concept of preservation. I’ve done this before and already know how it will go. When you do this exercise, you find something very interesting: The neuroscientist will begrudgingly admit that in order to have a long-term difference in behavior you must have synaptic-level changes in the nervous system. The biochemist will acknowledge that aldehydes like glutaraldehyde will retain essentially all nanostructure and proteins during fixation. The information theorist will admit that this is a sufficient condition for preservation. If anyone brings up objections along the lines of the dynamic activity of the brain being important, the clinician will be able to respond with clinical data from deep hypothermic circulatory arrest, ischemia, and other extreme brain conditions that conclusively show that the long-term memory is not stored in the dynamic activity of the brain. All of the knowledge to clearly derive that preservation is possible is there in the basic, 101-level facts in these fields. Almost all of the objections that each expert will have are simply ignorance of basic facts in fields not their own. The knowledge is out there, it’s just not common knowledge, because these fields aren’t good at talking to one another.

At the very least, I hope that OpenPhil will take this idea seriously enough to actually properly evaluate it, because it’s too important to continue to ignore.

Making preservation happen

I’ve already demonstrated essentially perfect preservation in rabbits and pigs, in a laboratory euthanasia setting. To make preservation a legitimate option for real people it must be made into a robust medical technique, able to deal with the many exceptional conditions that occur with each person at the end of their life.

Like introducing any new medical technique, it’s a complex task, but it’s by no means insurmountable. With enough funding and attention, it will be relatively straightforward to complete the additional research to determine the constraints under which preservation can be safely achieved in realistic settings.

We can start a clinical trial for preservation methods, studying the quality that can be achieved as well as the effect on the end-of-life experience. We can start extremely high quality brain banks that will further demonstrate quality and greatly accelerate research. We can fund high quality reviews of the literature to help establish shared knowledge. We can build partnerships with hospitals to offer opt-in emergency preservation for when their risky surgeries fail with no further recourse. We can create educational materials to help the general public understand the new option that is available to them. And looking back, we can know that we preserved the living memory of our generation and potentially saved the first lives for real.

Preservation can absolutely become a mainstream end-of-life option in a short number of years. I will work to make it happen whether or not OpenPhil is able to help. But I think the timeline could be accelerated with substantial funding and additional political will.

Useful Literature

1. https://nectome.com/the-case-for-glutaraldehyde-structural-encoding-and-preservation-of-long-term-memories/

2. Ostasiewicz, Paweł, et al. “Proteome, phosphoproteome, and N-glycoproteome are quantitatively preserved in formalin-fixed paraffin-embedded tissue and analyzable by high-resolution mass spectrometry.” Journal of proteome research (2010).

3. Hayashi-Takagi, Akiko, et al. “Labeling and optical erasure of synaptic memory traces in the motor cortex.” Nature (2015)

4. Percy, Andrew, et al. “Deep hypothermic circulatory arrest in patients with high cognitive needs: full preservation of cognitive abilities.” The Annals of thoracic surgery (2009)

5. McIntyre, Robert L., and Gregory M. Fahy. “Aldehyde-stabilized cryopreservation.” Cryobiology 71.3 (2015): 448-458.

[Cause Exploration Prizes] Human Engram Preservation as a Neglected Cause Area