Brain Preservation has two common definitions:
- To preserve the anatomical and cellular detail of a living brain, for scientific or research purposes.
- To keep the patterns of information that define a person and their memories safe from death and loss by preserving the brain when the body dies.
The Brain Preservation Foundation’s purpose is to encourage the development of technology which can preserve a human brain at biological death in such intricate detail that all of the cellular and connection information that makes up our memories and mind is preserved, to prevent informational death of the individual.
Disclaimer: We don’t preserve people at BPF, and we don’t advocate any particular preservation method or company.
We seek to assess the efficacy and affordability of any postmortem methods that preserve the neural circuitry of the human brain at nanometer scale. In concert with future understanding of the neural basis of memory by neuroscience, this work aims to validate methods that will reliably preserve our memories, experience, and individual identity at death. If brain preservation efficacy can be validated, we will advocate for the availability of affordable, high-quality preservation services around the world. BPF’s social mission is to help individuals preserve, use, and improve their brains to the greatest degree possible, both now and in the future.
Brain preservation can preserve what is completely lost at death today:
- We hope that brain preservation technology will one day become a viable alternative to death, available to everyone who might desire it. Instead of dying, you would have the medical option, and perhaps eventually the legal right, to have your brain preserved. The information that comprises your unique self can then be maintained indefinitely in your preserved brain until humanity develops the technology to revive you.
- Alternatively, for those who do not wish to be consciously revived in the future (restored to “self awareness”), brain preservation would give each of us the option to donate just our memories and personal histories to our loved ones, to science, or to society. Our memories are an incredibly rich legacy of knowledge and experience we may soon be able to leave for the next generation, if we wish. Via automated brain scanning, neuroscience, and neural modelling, we may be able to inexpensively read preserved human brains well enough to reconstruct either limited memories or full self-awareness in computers, as desired by the individual. Given current rapid progress in these technologies, inexpensive reconstruction might occur some time this century, while our loved ones are still alive.
- Whole human brain preservation enables many exciting areas of scientific and medical research, such as mapping the human connectome for better understanding human mental health and disease, and gathering data to better treat a broad array of brain disorders and diseases, such as autism, schizophrenia, and Alzheimer’s disease.
There are two use cases through which the scientific community presently considers the subject of brain preservation:
- Brain preservation for scientific and medical research uses.This use is generally noncontroversial, as it has been happening since the 1880’s, imperfectly for large brains, and near perfectly for very small sections of brain. As neuroscience, connectomics, and scanning technologies advance, chemopreservation and cryopreservation of increasingly large brain sections, and recently of whole animal brains, will continue to advance.
- Brain preservation for memory, experience, or identity preservation and later reanimation.This use is considered speculative by most scientists at present. Dozens of laboratories are today trying to understand the molecular basis of memory, and are using chemically preserved and cryopreserved brains to do so, along with other techniques. But there are many open questions that will have to be answered before it will be generally accepted that a well-preserved brain has retrievable memories, or more generally, is a preserved individual.
As the scientific and medical research use continues to grow, each of these uses may increasingly overlap, via preservation of brains for the purpose of the attempted retrieval of simple memories in animal models in neuroscience. As a result, those few who presently engage in the second use (cryonics patients, at present) and those who seek to validate or falsify brain preservation techniques (BPF and other organizations) will continue to introduce important scientific, ethical and legal questions to be resolved by future societies.
The full rules are here.
The competitors sent us (the Brain Preservation Foundation) preserved brains, and then we independently verified that the brains were preserved to our standards by taking multiple random samples and analyzing them with electron microscopy. If the resulting electron micrograph images looked good (i.e. no cracks, cell damage, etc) compared to reference images of healthy brain tissue, then we had a winner. To claim the prize, a contestant had to also publish the details of their method in a reputable scientific journal. Performing our verification procedure using electron microscopy required that the brain samples were fixed, embedded in plastic, and then sliced into very thin slices.
For chemopreserved brains, most of this procedure was already done. We simply received the plastic embedded brain, and did our own slicing and analysis.
For cryopreserved brains, we observed the vitrification process to ensure that the whole brain was preserved. Then we extracted small random samples from the thawed brain and used the standard small-scale plastic embedding procedure for preparing small samples for electron microscopy. Since it is much easier to plasticize very small samples of frozen brain tissue (it’s done all the time in labs across the world), evaluating cryopreserved brains this way put cryopreservation on a more equal footing with chemopreservation for the purposes of winning the prize.
A connectome is a comprehensive map of all the connections in a brain. It includes every neuron, every synapse, and every other incidental component of the network required to characterize the higher order information in the brain. The connectome describes how to build your memories, personality, and mind, just as the genome (which is all of the DNA of an individual), describes how to build your body.
The connectome is commonly defined in two ways:
- A technical definition of the connectome is often limited to the gross anatomical connections (how neurons connect to each other) in the brain. This alone is not considered fully sufficient to contain our unique memories and experiences.
- An expanded definition of the connectome includes not only the anatomical connections between neurons, but also the types and concentrations of special information-encoding molecules at each synapse (the “synaptome”), in the nucleus (the “epigenome”) and elsewhere in the neuron that may also store our unique memories, experiences, and individuality.
When BPF advisor Sebastian Seung says “I am my connectome,” he is using the expanded definition of the connectome. We use the word connectome in this expanded definition as well. See this talk by Professor Sebastian Seung for more details.
Perfusion is the process of introducing a chemical to the brain or other organs through the vascular system. It’s quite an efficient way to rapidly deliver chemicals, since the body is already designed to get blood close to every cell in your body to deliver oxygen and nutrients. All the neurons in your brain are especially close to blood vessels because they require a tremendous amount of sugar and oxygen to work. Both 21st Century Medicine and Dr. Mikula use perfusion to deliver their brain preserving chemicals to all parts of the brain, cryoprotectants in 21st Century’s case, and fixatives in Dr. Mikula’s case.
We all cherish our faces, hands, legs, and hearts as parts of who we are. But no part of you is more important than your brain. Within it is all of your memories, experiences, skills, preferences, and personality. Within it is you. To see that this is true, consider what parts of your body can be lost or replaced without changing who you are as a person. For example, people can and do have their internal organs such as the liver, heart, and intestines replaced with artificial or transplanted organs. Losing an arm or a leg is certainly devastating to a person’s life, but we do not treat a loved one who has lost an arm as a different person.
Of all your organs, only your brain is special – damage to the brain actually changes who a person is, either by destroying memories, by reducing cognitive function, or by altering personality. This is why we view the brain as both a necessary and sufficient object to preserve in order to preserve a person.
Current medical understanding says yes. A human brain can today survive being “shut down” for up to an hour in conditions of cold-water drowning, or for up to 40 minutes in the medical procedure of deep hypothermic circulatory arrest (stopping of the heart and circulation, after deep cooling of the body, in order to do cardiac surgeries). When the brain gets sufficiently cold in these conditions, there is no detectable electrical activity. If the cold is removed quickly, before too much biochemical decay occurs, the brain “reboots” and the person becomes conscious again, none the worse for wear.
The fact that people can recover completely from having their brains shut down by extreme cold tells us that our minds are not dependent on a continuous pattern of electrical activity, but instead depend on the special physical arrangement of cells and molecules in the brain.
Brain preservation takes the concept of temporary brain shutdown and extends the timeframe further. Instead of an hour of inactivity, the brain is kept inactive in a much more stable state for many years. Long-term brain preservation is technically much harder to accomplish than a brief shutdown, but the basic idea follows from what already occurs under the above special conditions. And since we already know that a mind can survive a short shutdown, it is reasonable to assume that a mind can also survive a very long shutdown. As long as the brain stays in the same physical state, it should not matter how many years of shutdown occur.
Current evidence suggests that it is. Because it appears that the human mind survives cessation of all electrical activity in the brain, it is clear that it is only a physical arrangement of special cells and molecules in the brain that is necessary to preserve the mind.
While preserving the brain’s connectome does not preserve the exact positions of every molecule in the brain, it is very likely that this is not important for the preservation of memories and mind. Much of the molecular activity in our brains is there to preserve the life of cells, not to hold high level information about the outside world. Only a special subset of neural activities, specifically the neural connections (synapses) and some molecular stores inside each neuron that modulate how the neuron talks to other neurons, appear to be involved in storing our unique thoughts, emotions, memories, experiences, self-awareness systems, and personality. Those connections are surprisingly redundant and fault-tolerant, which allows us to retain and rebuild our mental abilities throughout our lives, even as many of our neural connections suffer damage from aging, biochemical changes, and disease.
Recently, researchers have begun to determine what sorts of computations are taking place in neural tissue. Each time they have succeeded, they were able to replicate the behavior of the neural tissue with relatively simple computer models involving only the synaptic connections between neurons. These successes in a field called computational neuroscience tell us two things: First, they demonstrate that our thoughts and memories are stored as special patterns that have predictable causal relationships in the physical world. They are not dependent on the type of matter (computer hardware or biological matter). This is called the patternism hypothesis. Second, they help to put an upper limit on the complexity of brain systems involved in memory and mind, because if there was much more going on than what we simulate in our models, we would not be able to replicate behavior so well.
Have a look at the following articles and papers to get a feel for the requirements for simulating our unique neural computational processes, including our memories, personality, and identity:
- Article: Does Personal Identity Survive Cryopreservation?, Mike Darwin, 2011
- Article: Preserving the Self for Later Emulation: What Brain Features Do We Need?, John Smart, 2012
- Paper: Is the Brain a Quantum Computer? No. (PDF), Abninder Litt et.al., Cognitive Science, 2006
- Paper: Electron Imaging Tech For Whole Brain Neural Circuit Mapping (PDF), Ken Hayworth, 2012
Your brain contains the vast majority of your life’s memories about how your body moves and feels. From studying patients with Locked-In Syndrome, which happens after a massive brainstem stroke, we know that a person who has total loss of sensation and control of their body remains a normal, conscious person, someone who is patiently awaiting the arrival of medical science or technology that will “re-embody” them. They have lost whatever physical skills they may have learned, but they still have detailed memories of those skills, and normal thoughts and emotions.
In the future, the DNA in any cell may be used to reconstruct a body. But whether or how often body reconstruction will occur for any preserved person in the future is a question for future science. A robotic body, or the simulation of body and brain in a computer, may be a much earlier and more practical option for reanimation.
While the BPF focuses on brain preservation, companies that use the technology may combine it with other techniques to preserve the rest of the body, in accordance with the preferences of each individual.
Right now, Alcor will preserve your brain or your entire body using cryopreservation, which is the process of preserving an object using extreme cold. They currently (as of 2013) have 968 living people who have signed up to be cryopreserved, and have performed their cryopreservation procedure on 118 people. They have been around since the 1970’s, and are currently the largest cryopreservation institution. Other than Alcor, there is the smaller Cryonics Institute in Michigan, KrioRus in Russia, and a few even smaller companies in Australia and England. There are no commercial ventures performing chemopreservation on human brains at this time.
None of these groups have currently published evidence showing the level of connectome preservation necessary to win our challenge prize even in the best “laboratory” circumstances, therefore we remain skeptical of the quality of the procedures they offer. The Brain Preservation Foundation is working toward a future where organizations offering preservation services will be held to high standards of scientific proof of their core preservation procedures, as well as high standards of medical quality of care on an individual patient basis.
Revival scenarios have to be taken with a grain of salt, because predicting future technology is notoriously difficult. However, it does not seem like we need any fundamentally new technology to revive people from their preserved brains, just refinement of existing technology.
We could revive people using mind uploading, which involves making a high quality digital recreation of the brain and then simulating it on a computer. We already have the first stages of technology to do this, as we can preserve small sections of brain tissue, scan them with an electron microscope, trace out the neuronal connections using computer vision and manual human tracing, and even simulate the resulting system in simple models today. For examples, see Briggman, Helmstaedter, and Denk, 2011, Briggman and Bock, 2012, and Hayworth, 2012.
It is no longer implausible to imagine preserving a whole human brain, and then a few decades from now either scanning it nondestructively, in a future molecular-resolution MRI scanner, or cutting it into a million slices with an automated machine, and digitizing it in parallel using multibeam electron microscopes (destructive scanning), and then running the digitized brain on a very powerful computer. Though applying these techniques to a whole large animal brain is presently beyond our ability, we have been using destructive scanning techniques (FIBSEM, etc.) on very small animal brains for a few years now (zebrafish today, flies very soon) , though we don’t yet know how to extract memories from these digitally uploaded brain scans, as we haven’t yet cracked the long-term memory code for neocortex. But we do seem very close to understanding memory in hippocampus, our most ancient type of cortex, also called archecortex, an area of the brain used for storing short-term memory. For more, see computational neuroscientist Edmund Rolls’ publications. Getting to scans of larger animal brains, and extracting memories from these scans (simple ones in model organisms, at first) is a matter of engineering and incremental improvement over our current techniques. Specifically, we need faster computers, better brain preservation techniques, faster electron microscopes, better models in computational neuroscience of hippocampal and cortical memory, and better algorithms to process the vast amounts of data involved in a human connectome.
We could also revive people by restoring biological function. This may or may not be feasible depending on the exact way in which the brain is preserved. The idea is to reverse the damage done to brain by the preservation method and restore the brain to the same or better healthy biological state it was in before preservation. The restored brain would then be placed in a cloned or robotic body, or the preserved biological body would also be repaired at the molecular level. As preservation methods become more advanced and do less damage to the brain, it will become easier to reverse the damage and revive the brain. The ultimate achievement of this approach would be reversible preservation, where a person could be put into suspended animation and then revived at any time with no complications. Reversible preservation would be immensely useful for many applications such as organ banking, space travel, or emergency medical stabilization.
- Freezing damage When the brain freezes, ice crystals begin to develop in the extracellular space (ice does not form inside brain cells because there is much more water and ice nucleation material in the space outside and around neurons). The ice that forms is pure water, which causes the concentration of solutes in the remaining non-frozen water to skyrocket. Water leaves the cells, to restore osmotic balance, and the cells are crushed by the osmotic stress.
- Cryoprotectant damage and tissue dehydration Cryoprotectants help to prevent freezing damage. If there is a high enough concentration of cryoprotectant present in a piece of tissue when it begins to freeze, the water will become steadily more viscous and eventually transition to a solid, amorphous, glassy state instead of freezing. This glass transition or vitrification stops the crushing damage that would otherwise occur during freezing.Unfortunately, the concentration of cryoprotectant must be quite high to cause vitrification instead of freezing. At the concentrations required to protect the brain from freezing, the cryoprotectant is toxic. However, the toxicity of cryoprotectant is itself a function of temperature. The lower the temperature, the less toxic the cryoprotectant is. As the cryoprotectant is added to the brain, it exerts osmotic pressure, because the cryoprotectant solution has a higher concentration of solutes than the fluid that is normally in the brain. If the cryoprotectant is added too fast, it will cause brain cells to shrink and severely dehydrate them, possibly destroying neural ultrastructure.
Thus, adding cryoprotectant is a delicate balancing act between ramping up the concentration and lowering the temperature. Finding the right balance is a core challenge for cryopreservation. One proven way to prevent dehydration in small neural samples today is to first fix brain tissue via an aldehyde (chemopreservation) then to administer cryoprotectant and engage in cryopreservation. It is possible, though unverified today, that such a “hybrid” (chemo+cryo) technique may turn out to be the most reliable way to preserve neural ultrastructure for whole brains.
- Cracking As the brain is cooled to the glass transition temperature, it can sometimes crack mechanically. Using annealing can reduce the probability of cracking.
- Incomplete perfusion of cryoprotectant Cryoprotectant is delivered via perfusion. If the vasculature of the brain is damaged in some way, and the cryoprotectant does not reach a certain part of the brain, then that brain region will freeze instead of vitrify and be damaged by the crushing osmotic forces exerted by ice crystals.
- Cracking As the plastic resin hardens, it can crack and cause microscopic fissures in the preserved brain.
- Incomplete diffusion of fixative and other chemicals Initial fixatives are delivered via vascular perfusion. If the vasculature of the brain is damaged in some way, and these chemicals do not reach a certain part of the brain, then that brain region will be severely damaged during the water extraction and curing process. Later fixative, dehydration steps, and resin infiltration steps are today delivered via simple diffusion (the whole brain being immersed in a chemical bath). Diffusion of chemicals into large blocks of tissue can be problematic and has only been demonstrated on volumes the size of a mouse brain so far.
- Toxicity and and cost of preservation chemicals Most of the brain preservation chemicals, such as glutaraldehyde, which fixes (crosslinks) proteins are relatively inexpensive and only mildly toxic. But the chemical currently most favored for fixing fats, osmium tetroxide, is both strongly toxic and expensive. Unless a substitute to osmium can be found, its cost alone may end up being the majority cost of the procedure. Several osmium substitutes currently exist, but their fat-fixing abilities are less effective, and it is not yet known what level of fat fixation will be sufficient to preserve the information of memory and identity. One new brain preservation method, CLARITY, removes fats altogether from whole small animal brains and replaces them with a hydrogel. It is not yet known whether this process can be scaled to a human brain, or whether such a brain would still contain the critical ultrastructure of memory and identity.
- Water removal and plastination Presently, the final step in chemopreservation involves water removal via organic solvent extraction, and infiltration of the brain with plastic resin. It is not yet known whether this step involves the loss of any critical molecular features of memory and identity. If so, chemopreservation followed by vacuum dehydration or by cryopreservation (a hybrid technique) may become a leading brain preservation technique.
Brain preservation cost will likely vary greatly by country and service offering. Some complex medical procedures (dental work, orthopedic surgery, transplants, fertility treatments, etc.) are available as much as ten times cheaper in specialty countries, a condition that has led to a multi-billion dollar medical tourism industry in recent years. Brain preservation services offered in elder residence or hospice centers in developing nations, for example, could be offered at far lower cost than in the US. Those using Alcor for cryopreservation today must take out (and on average, prepay over time) a life insurance policy that pays $80,000 at death for neuropreservation, or $200,000 for whole body preservation. Three-quarters of Alcor’s patients have opted for the cheaper option. Neuropreservation is also offered by KrioRus, a Russian cryonics company, for $12,000. Alcor had 118 patients, and KrioRus 25 patients in 2013. This shows the wide variation in current costs today, when brain preservation is in a Very Early Adopter phase. Costs will surely go both lower and higher in the future, as services variety, innovation, and adoption grows.
The Brain Preservation Technology Prize rules specify that the winning team must submit a brain preservation procedure that “with minor modifications, might potentially be offered for less than $20,000 by appropriately trained medical professionals.” This is an estimated cost of brain chemopreservation or cryopreservation by appropriately trained medical personnel, and includes any necessary storage costs after death. This cost is not specific to any country, and it does not include the cost of medical standby prior to death, which can be very little or very expensive, depending on each individual’s end-of-life arrangements. It also does not include any future costs of memory or identity reanimation. The prize winner must simply make a reasonable case that a service provider using their procedure might be able to do medically-supervised preservation and any necessary storage at this price, in any country in the world. This target cost has been picked as a worthy technical accomplishment, based on estimated cost of necessary specialist labor and materials. In combination with neuroscientific localization of memory in the connectome in animal models, we expect that winning the Prize as structured should help grow global demand, access and affordability of brain preservation services.
In lowering costs, cryopreservation has the present advantages of significant technical knowledge gained over fifty years of experimentation, but the disadvantage of higher storage costs, due to the need for dewars and ongoing supply of liquid nitrogen. Chemopreservation has the advantage of no necessary storage costs after death, but the disadvantage of little technical experience with whole brain preservation to date, and the toxicity of the preservation chemicals involved.
- You can sign our online petition, and leave your comments for others to see.
- You can volunteer. The BPF is run by volunteers and we could use your talents!
- Tell your friends about us via our Facebook, Twitter, and talk to them about the need for brain preservation technology.
- Be respectful of each individual’s end of life decisions, but demand, for all who might wish it around the world, the existence of a validated and affordable brain preservation option at death.
Read our “你能帮什么忙” page for more information.
Brain Preservation has two common definitions:
- To preserve the anatomical and cellular detail of a living brain, for scientific or research purposes.
- To keep the patterns of information that define a person and their memories safe from death and loss by preserving the brain when the body dies.
The Brain Preservation Foundation’s purpose is to encourage the development of technology which can preserve a human brain at biological death in such intricate detail that all of the cellular and connection information that makes up our memories and mind is preserved, to prevent informational death of the individual.
Disclaimer: We don’t preserve people at BPF, and we don’t advocate any particular preservation method or company.
We seek to assess the efficacy and affordability of any postmortem methods that preserve the neural circuitry of the human brain at nanometer scale. In concert with future understanding of the neural basis of memory by neuroscience, this work aims to validate methods that will reliably preserve our memories, experience, and individual identity at death. If brain preservation efficacy can be validated, we will advocate for the availability of affordable, high-quality preservation services around the world. BPF’s social mission is to help individuals preserve, use, and improve their brains to the greatest degree possible, both now and in the future.
Brain preservation can preserve what is completely lost at death today:
- We hope that brain preservation technology will one day become a viable alternative to death, available to everyone who might desire it. Instead of dying, you would have the medical option, and perhaps eventually the legal right, to have your brain preserved. The information that comprises your unique self can then be maintained indefinitely in your preserved brain until humanity develops the technology to revive you.
- Alternatively, for those who do not wish to be consciously revived in the future (restored to “self awareness”), brain preservation would give each of us the option to donate just our memories and personal histories to our loved ones, to science, or to society. Our memories are an incredibly rich legacy of knowledge and experience we may soon be able to leave for the next generation, if we wish. Via automated brain scanning, neuroscience, and neural modelling, we may be able to inexpensively read preserved human brains well enough to reconstruct either limited memories or full self-awareness in computers, as desired by the individual. Given current rapid progress in these technologies, inexpensive reconstruction might occur some time this century, while our loved ones are still alive.
- Whole human brain preservation enables many exciting areas of scientific and medical research, such as mapping the human connectome for better understanding human mental health and disease, and gathering data to better treat a broad array of brain disorders and diseases, such as autism, schizophrenia, and Alzheimer’s disease.
There are two use cases through which the scientific community presently considers the subject of brain preservation:
- Brain preservation for scientific and medical research uses.This use is generally noncontroversial, as it has been happening since the 1880’s, imperfectly for large brains, and near perfectly for very small sections of brain. As neuroscience, connectomics, and scanning technologies advance, chemopreservation and cryopreservation of increasingly large brain sections, and recently of whole animal brains, will continue to advance.
- Brain preservation for memory, experience, or identity preservation and later reanimation.This use is considered speculative by most scientists at present. Dozens of laboratories are today trying to understand the molecular basis of memory, and are using chemically preserved and cryopreserved brains to do so, along with other techniques. But there are many open questions that will have to be answered before it will be generally accepted that a well-preserved brain has retrievable memories, or more generally, is a preserved individual.
As the scientific and medical research use continues to grow, each of these uses may increasingly overlap, via preservation of brains for the purpose of the attempted retrieval of simple memories in animal models in neuroscience. As a result, those few who presently engage in the second use (cryonics patients, at present) and those who seek to validate or falsify brain preservation techniques (BPF and other organizations) will continue to introduce important scientific, ethical and legal questions to be resolved by future societies.
The full rules are here.
The competitors sent us (the Brain Preservation Foundation) preserved brains, and then we independently verified that the brains were preserved to our standards by taking multiple random samples and analyzing them with electron microscopy. If the resulting electron micrograph images looked good (i.e. no cracks, cell damage, etc) compared to reference images of healthy brain tissue, then we had a winner. To claim the prize, a contestant had to also publish the details of their method in a reputable scientific journal. Performing our verification procedure using electron microscopy required that the brain samples were fixed, embedded in plastic, and then sliced into very thin slices.
For chemopreserved brains, most of this procedure was already done. We simply received the plastic embedded brain, and did our own slicing and analysis.
For cryopreserved brains, we observed the vitrification process to ensure that the whole brain was preserved. Then we extracted small random samples from the thawed brain and used the standard small-scale plastic embedding procedure for preparing small samples for electron microscopy. Since it is much easier to plasticize very small samples of frozen brain tissue (it’s done all the time in labs across the world), evaluating cryopreserved brains this way put cryopreservation on a more equal footing with chemopreservation for the purposes of winning the prize.
A connectome is a comprehensive map of all the connections in a brain. It includes every neuron, every synapse, and every other incidental component of the network required to characterize the higher order information in the brain. The connectome describes how to build your memories, personality, and mind, just as the genome (which is all of the DNA of an individual), describes how to build your body.
The connectome is commonly defined in two ways:
- A technical definition of the connectome is often limited to the gross anatomical connections (how neurons connect to each other) in the brain. This alone is not considered fully sufficient to contain our unique memories and experiences.
- An expanded definition of the connectome includes not only the anatomical connections between neurons, but also the types and concentrations of special information-encoding molecules at each synapse (the “synaptome”), in the nucleus (the “epigenome”) and elsewhere in the neuron that may also store our unique memories, experiences, and individuality.
When BPF advisor Sebastian Seung says “I am my connectome,” he is using the expanded definition of the connectome. We use the word connectome in this expanded definition as well. See this talk by Professor Sebastian Seung for more details.
Perfusion is the process of introducing a chemical to the brain or other organs through the vascular system. It’s quite an efficient way to rapidly deliver chemicals, since the body is already designed to get blood close to every cell in your body to deliver oxygen and nutrients. All the neurons in your brain are especially close to blood vessels because they require a tremendous amount of sugar and oxygen to work. Both 21st Century Medicine and Dr. Mikula use perfusion to deliver their brain preserving chemicals to all parts of the brain, cryoprotectants in 21st Century’s case, and fixatives in Dr. Mikula’s case.
We all cherish our faces, hands, legs, and hearts as parts of who we are. But no part of you is more important than your brain. Within it is all of your memories, experiences, skills, preferences, and personality. Within it is you. To see that this is true, consider what parts of your body can be lost or replaced without changing who you are as a person. For example, people can and do have their internal organs such as the liver, heart, and intestines replaced with artificial or transplanted organs. Losing an arm or a leg is certainly devastating to a person’s life, but we do not treat a loved one who has lost an arm as a different person.
Of all your organs, only your brain is special – damage to the brain actually changes who a person is, either by destroying memories, by reducing cognitive function, or by altering personality. This is why we view the brain as both a necessary and sufficient object to preserve in order to preserve a person.
Current medical understanding says yes. A human brain can today survive being “shut down” for up to an hour in conditions of cold-water drowning, or for up to 40 minutes in the medical procedure of deep hypothermic circulatory arrest (stopping of the heart and circulation, after deep cooling of the body, in order to do cardiac surgeries). When the brain gets sufficiently cold in these conditions, there is no detectable electrical activity. If the cold is removed quickly, before too much biochemical decay occurs, the brain “reboots” and the person becomes conscious again, none the worse for wear.
The fact that people can recover completely from having their brains shut down by extreme cold tells us that our minds are not dependent on a continuous pattern of electrical activity, but instead depend on the special physical arrangement of cells and molecules in the brain.
Brain preservation takes the concept of temporary brain shutdown and extends the timeframe further. Instead of an hour of inactivity, the brain is kept inactive in a much more stable state for many years. Long-term brain preservation is technically much harder to accomplish than a brief shutdown, but the basic idea follows from what already occurs under the above special conditions. And since we already know that a mind can survive a short shutdown, it is reasonable to assume that a mind can also survive a very long shutdown. As long as the brain stays in the same physical state, it should not matter how many years of shutdown occur.
Current evidence suggests that it is. Because it appears that the human mind survives cessation of all electrical activity in the brain, it is clear that it is only a physical arrangement of special cells and molecules in the brain that is necessary to preserve the mind.
While preserving the brain’s connectome does not preserve the exact positions of every molecule in the brain, it is very likely that this is not important for the preservation of memories and mind. Much of the molecular activity in our brains is there to preserve the life of cells, not to hold high level information about the outside world. Only a special subset of neural activities, specifically the neural connections (synapses) and some molecular stores inside each neuron that modulate how the neuron talks to other neurons, appear to be involved in storing our unique thoughts, emotions, memories, experiences, self-awareness systems, and personality. Those connections are surprisingly redundant and fault-tolerant, which allows us to retain and rebuild our mental abilities throughout our lives, even as many of our neural connections suffer damage from aging, biochemical changes, and disease.
Recently, researchers have begun to determine what sorts of computations are taking place in neural tissue. Each time they have succeeded, they were able to replicate the behavior of the neural tissue with relatively simple computer models involving only the synaptic connections between neurons. These successes in a field called computational neuroscience tell us two things: First, they demonstrate that our thoughts and memories are stored as special patterns that have predictable causal relationships in the physical world. They are not dependent on the type of matter (computer hardware or biological matter). This is called the patternism hypothesis. Second, they help to put an upper limit on the complexity of brain systems involved in memory and mind, because if there was much more going on than what we simulate in our models, we would not be able to replicate behavior so well.
Have a look at the following articles and papers to get a feel for the requirements for simulating our unique neural computational processes, including our memories, personality, and identity:
- Article: Does Personal Identity Survive Cryopreservation?, Mike Darwin, 2011
- Article: Preserving the Self for Later Emulation: What Brain Features Do We Need?, John Smart, 2012
- Paper: Is the Brain a Quantum Computer? No. (PDF), Abninder Litt et.al., Cognitive Science, 2006
- Paper: Electron Imaging Tech For Whole Brain Neural Circuit Mapping (PDF), Ken Hayworth, 2012
Your brain contains the vast majority of your life’s memories about how your body moves and feels. From studying patients with Locked-In Syndrome, which happens after a massive brainstem stroke, we know that a person who has total loss of sensation and control of their body remains a normal, conscious person, someone who is patiently awaiting the arrival of medical science or technology that will “re-embody” them. They have lost whatever physical skills they may have learned, but they still have detailed memories of those skills, and normal thoughts and emotions.
In the future, the DNA in any cell may be used to reconstruct a body. But whether or how often body reconstruction will occur for any preserved person in the future is a question for future science. A robotic body, or the simulation of body and brain in a computer, may be a much earlier and more practical option for reanimation.
While the BPF focuses on brain preservation, companies that use the technology may combine it with other techniques to preserve the rest of the body, in accordance with the preferences of each individual.
Right now, Alcor will preserve your brain or your entire body using cryopreservation, which is the process of preserving an object using extreme cold. They currently (as of 2013) have 968 living people who have signed up to be cryopreserved, and have performed their cryopreservation procedure on 118 people. They have been around since the 1970’s, and are currently the largest cryopreservation institution. Other than Alcor, there is the smaller Cryonics Institute in Michigan, KrioRus in Russia, and a few even smaller companies in Australia and England. There are no commercial ventures performing chemopreservation on human brains at this time.
None of these groups have currently published evidence showing the level of connectome preservation necessary to win our challenge prize even in the best “laboratory” circumstances, therefore we remain skeptical of the quality of the procedures they offer. The Brain Preservation Foundation is working toward a future where organizations offering preservation services will be held to high standards of scientific proof of their core preservation procedures, as well as high standards of medical quality of care on an individual patient basis.
Revival scenarios have to be taken with a grain of salt, because predicting future technology is notoriously difficult. However, it does not seem like we need any fundamentally new technology to revive people from their preserved brains, just refinement of existing technology.
We could revive people using mind uploading, which involves making a high quality digital recreation of the brain and then simulating it on a computer. We already have the first stages of technology to do this, as we can preserve small sections of brain tissue, scan them with an electron microscope, trace out the neuronal connections using computer vision and manual human tracing, and even simulate the resulting system in simple models today. For examples, see Briggman, Helmstaedter, and Denk, 2011, Briggman and Bock, 2012, and Hayworth, 2012.
It is no longer implausible to imagine preserving a whole human brain, and then a few decades from now either scanning it nondestructively, in a future molecular-resolution MRI scanner, or cutting it into a million slices with an automated machine, and digitizing it in parallel using multibeam electron microscopes (destructive scanning), and then running the digitized brain on a very powerful computer. Though applying these techniques to a whole large animal brain is presently beyond our ability, we have been using destructive scanning techniques (FIBSEM, etc.) on very small animal brains for a few years now (zebrafish today, flies very soon) , though we don’t yet know how to extract memories from these digitally uploaded brain scans, as we haven’t yet cracked the long-term memory code for neocortex. But we do seem very close to understanding memory in hippocampus, our most ancient type of cortex, also called archecortex, an area of the brain used for storing short-term memory. For more, see computational neuroscientist Edmund Rolls’ publications. Getting to scans of larger animal brains, and extracting memories from these scans (simple ones in model organisms, at first) is a matter of engineering and incremental improvement over our current techniques. Specifically, we need faster computers, better brain preservation techniques, faster electron microscopes, better models in computational neuroscience of hippocampal and cortical memory, and better algorithms to process the vast amounts of data involved in a human connectome.
We could also revive people by restoring biological function. This may or may not be feasible depending on the exact way in which the brain is preserved. The idea is to reverse the damage done to brain by the preservation method and restore the brain to the same or better healthy biological state it was in before preservation. The restored brain would then be placed in a cloned or robotic body, or the preserved biological body would also be repaired at the molecular level. As preservation methods become more advanced and do less damage to the brain, it will become easier to reverse the damage and revive the brain. The ultimate achievement of this approach would be reversible preservation, where a person could be put into suspended animation and then revived at any time with no complications. Reversible preservation would be immensely useful for many applications such as organ banking, space travel, or emergency medical stabilization.
- Freezing damage When the brain freezes, ice crystals begin to develop in the extracellular space (ice does not form inside brain cells because there is much more water and ice nucleation material in the space outside and around neurons). The ice that forms is pure water, which causes the concentration of solutes in the remaining non-frozen water to skyrocket. Water leaves the cells, to restore osmotic balance, and the cells are crushed by the osmotic stress.
- Cryoprotectant damage and tissue dehydration Cryoprotectants help to prevent freezing damage. If there is a high enough concentration of cryoprotectant present in a piece of tissue when it begins to freeze, the water will become steadily more viscous and eventually transition to a solid, amorphous, glassy state instead of freezing. This glass transition or vitrification stops the crushing damage that would otherwise occur during freezing.Unfortunately, the concentration of cryoprotectant must be quite high to cause vitrification instead of freezing. At the concentrations required to protect the brain from freezing, the cryoprotectant is toxic. However, the toxicity of cryoprotectant is itself a function of temperature. The lower the temperature, the less toxic the cryoprotectant is. As the cryoprotectant is added to the brain, it exerts osmotic pressure, because the cryoprotectant solution has a higher concentration of solutes than the fluid that is normally in the brain. If the cryoprotectant is added too fast, it will cause brain cells to shrink and severely dehydrate them, possibly destroying neural ultrastructure.
Thus, adding cryoprotectant is a delicate balancing act between ramping up the concentration and lowering the temperature. Finding the right balance is a core challenge for cryopreservation. One proven way to prevent dehydration in small neural samples today is to first fix brain tissue via an aldehyde (chemopreservation) then to administer cryoprotectant and engage in cryopreservation. It is possible, though unverified today, that such a “hybrid” (chemo+cryo) technique may turn out to be the most reliable way to preserve neural ultrastructure for whole brains.
- Cracking As the brain is cooled to the glass transition temperature, it can sometimes crack mechanically. Using annealing can reduce the probability of cracking.
- Incomplete perfusion of cryoprotectant Cryoprotectant is delivered via perfusion. If the vasculature of the brain is damaged in some way, and the cryoprotectant does not reach a certain part of the brain, then that brain region will freeze instead of vitrify and be damaged by the crushing osmotic forces exerted by ice crystals.
- Cracking As the plastic resin hardens, it can crack and cause microscopic fissures in the preserved brain.
- Incomplete diffusion of fixative and other chemicals Initial fixatives are delivered via vascular perfusion. If the vasculature of the brain is damaged in some way, and these chemicals do not reach a certain part of the brain, then that brain region will be severely damaged during the water extraction and curing process. Later fixative, dehydration steps, and resin infiltration steps are today delivered via simple diffusion (the whole brain being immersed in a chemical bath). Diffusion of chemicals into large blocks of tissue can be problematic and has only been demonstrated on volumes the size of a mouse brain so far.
- Toxicity and and cost of preservation chemicals Most of the brain preservation chemicals, such as glutaraldehyde, which fixes (crosslinks) proteins are relatively inexpensive and only mildly toxic. But the chemical currently most favored for fixing fats, osmium tetroxide, is both strongly toxic and expensive. Unless a substitute to osmium can be found, its cost alone may end up being the majority cost of the procedure. Several osmium substitutes currently exist, but their fat-fixing abilities are less effective, and it is not yet known what level of fat fixation will be sufficient to preserve the information of memory and identity. One new brain preservation method, CLARITY, removes fats altogether from whole small animal brains and replaces them with a hydrogel. It is not yet known whether this process can be scaled to a human brain, or whether such a brain would still contain the critical ultrastructure of memory and identity.
- Water removal and plastination Presently, the final step in chemopreservation involves water removal via organic solvent extraction, and infiltration of the brain with plastic resin. It is not yet known whether this step involves the loss of any critical molecular features of memory and identity. If so, chemopreservation followed by vacuum dehydration or by cryopreservation (a hybrid technique) may become a leading brain preservation technique.
Brain preservation cost will likely vary greatly by country and service offering. Some complex medical procedures (dental work, orthopedic surgery, transplants, fertility treatments, etc.) are available as much as ten times cheaper in specialty countries, a condition that has led to a multi-billion dollar medical tourism industry in recent years. Brain preservation services offered in elder residence or hospice centers in developing nations, for example, could be offered at far lower cost than in the US. Those using Alcor for cryopreservation today must take out (and on average, prepay over time) a life insurance policy that pays $80,000 at death for neuropreservation, or $200,000 for whole body preservation. Three-quarters of Alcor’s patients have opted for the cheaper option. Neuropreservation is also offered by KrioRus, a Russian cryonics company, for $12,000. Alcor had 118 patients, and KrioRus 25 patients in 2013. This shows the wide variation in current costs today, when brain preservation is in a Very Early Adopter phase. Costs will surely go both lower and higher in the future, as services variety, innovation, and adoption grows.
The Brain Preservation Technology Prize rules specify that the winning team must submit a brain preservation procedure that “with minor modifications, might potentially be offered for less than $20,000 by appropriately trained medical professionals.” This is an estimated cost of brain chemopreservation or cryopreservation by appropriately trained medical personnel, and includes any necessary storage costs after death. This cost is not specific to any country, and it does not include the cost of medical standby prior to death, which can be very little or very expensive, depending on each individual’s end-of-life arrangements. It also does not include any future costs of memory or identity reanimation. The prize winner must simply make a reasonable case that a service provider using their procedure might be able to do medically-supervised preservation and any necessary storage at this price, in any country in the world. This target cost has been picked as a worthy technical accomplishment, based on estimated cost of necessary specialist labor and materials. In combination with neuroscientific localization of memory in the connectome in animal models, we expect that winning the Prize as structured should help grow global demand, access and affordability of brain preservation services.
In lowering costs, cryopreservation has the present advantages of significant technical knowledge gained over fifty years of experimentation, but the disadvantage of higher storage costs, due to the need for dewars and ongoing supply of liquid nitrogen. Chemopreservation has the advantage of no necessary storage costs after death, but the disadvantage of little technical experience with whole brain preservation to date, and the toxicity of the preservation chemicals involved.
- You can sign our online petition, and leave your comments for others to see.
- You can volunteer. The BPF is run by volunteers and we could use your talents!
- Tell your friends about us via our Facebook, Twitter, and talk to them about the need for brain preservation technology.
- Be respectful of each individual’s end of life decisions, but demand, for all who might wish it around the world, the existence of a validated and affordable brain preservation option at death.
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