Connectome: How the Brain’s Wiring Makes Us Who We Are

A Review

Connectome: How the Brain’s Wiring Makes Us Who We Are by Sebastian Seung, Houghton Mifflin Harcourt Trade, 384 pages, 2012.

The scientific perspective that informs Sebastian Seung’s bestselling popular neuroscience book Connectome is so familiar to cryonicists that the bulk of this book could be mistaken for an extensive introduction to the philosophy of mind embodied in cryonics. His book offers a rigorous exposition of the view that our identity is encoded in the connections between neurons, the “connectome,” which itself is shaped by our genes and life experience. The strength of this book is not only its review of the empirical evidence that supports this outlook but its encouraging the reader to think about its implications. Readers who are intimately familiar with the argument in favor of cryonics should not assume that there is little to learn from this book. As imaging and storage technologies evolve, cryonicists can do more now than in the past to learn about their individual connectome, strengthening the likelihood of successful resuscitation.

One important element of the connectionist premise that structures Seung’s book is that it does not completely resolve competing theories about how the brain works. For example, the recognition that long-term memory (and identity) does not depend on transient electrical activity but has a more robust long-term physical basis that persists during cessation of brain activity (examples are hypothermic circulatory arrest and short periods of cardiac arrest) does not imply a single perspective on how the genome provides the neurological bases for memory formation, retention, recollection, and re-prioritization. One interesting perspective, “neural Darwinism,” which was anticipated by the economist Friedrich Hayek, proposes a theory of brain function in which a genetically determined wiring of the brain is subject to competing experiences that strengthen or weaken populations of synapses throughout life. One of the interesting implications of this theory is that consciousness can be treated as an emergent outcome of micro-events in the brain, instead of a mysterious, autonomous property of the brain (think of the curious concept of “free will”).

Seung devotes two chapters to the nature-nurture debate through a connectionist perspective. One of the unfortunate effects of the nature-nurture distinction is that it masks the obvious point that what we call “nurture” (upbringing, environment, etc.) is not exempt from biology but simply concerns the relationship between biological systems and between a biological system and its physical environment. Social scientists who have a strong “nurture”-bias should therefore not be exempted from describing “nurture” in verifiable physical terms, something that many of them do not feel the slightest obligation to do. Another unattractive feature of this debate is that it is routinely portrayed as one between genetic determinists and “environmentalists.” In reality, the debate is mostly between serious scholars who acknowledge that behavior and learning are shaped by both genetics and the environment and those who basically consider the mind a blank slate—a position that is clearly contradicted by existing science but remains popular as a premise in contemporary public policy and certain political ideologies. One of the interesting topics that Seung discusses in these chapters is whether the plasticity of the brain changes over time.

From the perspective of cryonics, the relationship between the genome and the connectome is of great importance. If some of the basic wiring of the brain that encodes personality and temperament is determined by genes and is fixed (or mostly fixed) at an early age, then some parts of the connectome might be inferred from a person’s genome, which opens up an exciting research program for cryonics. A systematic study of the field where genetics meets neurodevelopment might help in understanding the relationship between the genome and brain ultrastructure. This in turn could assist in future resuscitation attempts. To date, the assumption in cryonics has been that the complete ultrastructure of the patient must be preserved (or at least preserved in such a manner that it can be inferred), but if some of it can be inferred from the genome the repair requirements for resuscitation of cryonics patients may be relaxed. Looking for such invariable features in variable brains is an important element of a credible cryonics resuscitation research program.

The power of comparing connectomes is also recognized by Seung in a separate chapter (“Comparing”). There he reviews technologies and approaches to compare connectomes with the goal of understanding personality differences and understanding neuropathologies or “connectopathies.” This chapter is one of several in which the author reviews the existing and emerging technologies that are enabling us to produce a complete connectome, including the innovative equipment of brain preservation advocate member Kenneth Hayworth to perform serial electron microscopy. Also discussed are technologies such as diffusion MRI (dMRI), which allows for non-invasive mapping of the connectome at the macro scale using water as a probe. This technology may not be adequate to map the connectome at the cellular level but its contribution to comparative connectomics has already been recognized. It may also hold promise as a means to collect identity-critical information about an individual while alive, which again may lessen the computational challenges involved in cryonics resuscitation. One of the exciting prospects of the field of connectomics is that it can contribute to a further narrowing of the challenges involved in restoring cryonics patients to good health.

Seung closes his chapters on emerging technologies with a review of the prospects of connectomics for the treatment of neurological diseases. One of the potential treatments involves the re-programming of a person’s own (skin) cells to neurons, which can then be introduced in the brain to treat a disease or enhance brain function. Such an approach may also be used to fill the “missing gaps” in the brain of a cryonics patient (alternative technologies include molecular construction of neurons by advanced molecular nanotech­nology).

At this point, I think we can foresee a rather optimistic future for cryonics research and the prospect of resuscitation. Instead of conceptualizing cryonics as the preservation of clinically dead people in the hope that future medicine can restore these people to good health, we can envision a more complex, but more encouraging, path. The work of resuscitation and restoring identity is not something that is expected to occur exclusively in the future but rather will be an ongoing process that starts as soon as the patient is cryopreserved. And with the rise of advanced genomics and non-destructive imaging technologies, some of the initial work can be done while the person is still alive. One of the exciting aspects of being a cryonicist today is that you can take proactive steps to learn about your own connectome and other identity-relevant information.

Seung devotes no less than a whole chapter to human cryopreservation (and the associated idea of chemopreservation). The author recognizes that his own views about the connectome are so similar to the philosophy of mind that underpins cryonics that he needs to do some justice to the rationale of cryonics. One unfortunate aspect is that he situates his discussion of cryonics in the context of religion and immortality. It is undeniable that some cryonicists are motivated by visions of personal immortality but this idea is not intrinsic to cryonics (neither is mind uploading or transhumanism.) Properly conceived, cryonics is an experimental medical procedure that aims to stabilize patients at cryogenic temperatures in anticipation of future treatment. What really distinguishes cryonics from mainstream medicine is not uncertainty (which is a fact of life), but the temporal separation of stabilization and treatment. One regrettable implication of attributing religious motives to people who make cryonics arrangements is that it cheapens the use of the word ‘religious.’ Instead of referring to worship of a higher being, it is here used as a strong belief in something in the absence of conclusive evidence. But by putting the bar so low, Seung (unintentionally) classifies many aspects of life, including choosing novel experimental treatments in mainstream medicine, as “religious.”

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What really distinguishes cryonics from mainstream medicine is not uncertainty (which is a fact of life), but the temporal separation of stabilization and treatment

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At one point Seung writes that research aimed at demonstrating that contemporary vitrification technologies can preserve the connectome will “finally bring some science to Ettinger’s wager.” This is a remarkable statement because even the earliest arguments in favor of cryonics were never presented in the form of a pure wager. In his book The Prospect of Immortality, Robert Ettinger reviews existing evidence from cryobiology and neuroscience and argues that, combined with the expectation that medicine will continue to evolve, the choice to be cryopreserved is a rational decision. Since Ettinger’s book cryonics organizations and wealthy donors have expended a lot of money and time in perfecting preservation techniques and looking at the effects of new technologies on the structure and viability of the brain. Compared to the state of, let’s say, interventive biogerontology, the scientific progress that has been made in cryonics is not trivial. For example, it is doubtful whether the widespread adoption of vitrification in mainstream cryobiology would have been possible without sustained research into using this approach for complex organs by cryonics supporters. To my knowledge, cryonicists have always been quite eager to generate experimental knowledge to inform their decision making. Now that more advanced technologies to map the human brain are becoming available, cryonics organizations are eager to use them instead of just passively maintaining their “faith.”

Ultimately, Seung still fails to recognize that cryonics inherently involves an element of uncertainty that cannot be eliminated without it not being cryonics anymore (i.e., elimination of uncertainty makes it suspended animation). To his credit, the author recognizes that it is not necessary for a preservation technology to perfectly preserve the connectome as long as it remains possible to infer the original state (or missing information) from what has been preserved. We can speculate what the limits of such “neural archeology” will be, but I do not think anyone can make conclusive arguments. In this sense, cryonics cannot be completely moved from the realm of informed decision making into the realm of indisputable fact. An element of uncertainty will always be associated with it, even if the experimental evidence in favor of this medical procedure keeps mounting.

The author also discusses alternative preservation approaches such as chemical fixation and plastination. One drawback of existing chemical preservation technologies is that they are irreversible by contemporary techniques (literally a “dead end”) and do not permit whole organism functional recovery.

There is one formidable challenge that will inevitably arise if chemical preservation is offered as a means of personal survival. It is how to deal with the fact that if chemical fixation is delayed, perfusion impairment in the brain will prevent complete cross-linking of biomolecules. Chemopreservation requires that the procedure be started prior to, or immediately following, circulatory arrest. In absence of this, the fate of a person’s connectome is uncertain, and may even worsen during storage—a problem cryonics is exempt from. This can be mitigated by complementary immersion fixation and/or ultra-low temperature storage but this introduces all the kinds of complexities and trade-offs that have traditionally been associated with cryonics. Clinical chemopreservation also requires traditional Standby, Stabilization, and Transport (SST) procedures to bring most cases in the realm of good preservation.

One interesting consequence of thinking about preservation and evidence from a connectomics perspective is that it provides a powerful framework how to think about evidence. Obtaining a few good electron micrographs from the brain can co-exist with poor preservation in other areas. Good viability (even whole-brain tests like EEG) can co-exist with regional compromise of viability. It is not possible to present a complete connectome for each experimental or clinical case at this point in time. In that sense research aimed at complete long-term functional survival (like the CryoDAO CryoRat project) still remains an important benchmark.

The book ends with a chapter about mind uploading. One misconception about cryonics is that people seek it as a means to mind uploading, or that reviving the person in a computer is the aim of cryonics. In fact, the late Robert Ettinger became a vocal critic of mind uploading in his final years. He offered a lot of arguments for his skepticism but his main concern was that questions about the feasibility of mind uploading are ultimately empirical questions which cannot be settled by deductive reasoning and dogmatic claims about the nature of the mind or consciousness. One of the amusing aspects of the debate about mind uploading is that proponents and skeptics both accuse the other of not being consistent materialists. Interestingly enough, Seung makes an observation relevant to this debate when he writes how the idea that “information is the new soul” is implied in the mind uploading project.

Despite some misgivings about how Seung presents and conceptualizes cryonics, I am unaware of another book that offers such a clear exposition of the relationship between brain and identity that informs human cryopreservation (and chemopreservation). The most rewarding thing for me was a stronger recognition that the idea of the connectome is not just a premise but opens the door to multiple fruitful research programs aimed at personal survival.

About the Author: Sebastian Seung is Professor of Computational Neuroscience and Physics at MIT and Investigator at the Howard Hughes Medical Institute. He has made important advances in artificial intelligence and neuroscience. His research has been published in leading scientific journals and also featured in the New York Times, Technology Review, and the Economist. (From the dust jacket.)

Dr. Seung was also a speaker at the Alcor-40 conference in October 2012

[This slightly revised and expanded review originally appeared in Venturist News and Views, June-July 2012, 6-7 and Cryonics, September-October 2012]