The wiring diagram of a human brain revealing connections. Courtesy of the consortium of The Human Connectome Project

Essay/
Neuroscience

The wiring diagram of a human brain revealing connections. Courtesy of the consortium of The Human Connectome Project

Am I my connectome?

Each human brain possesses a unique, intricate pattern of 86 billion neurons. If science can map it, immortality beckons

Phil Jaekl

The wiring diagram of a human brain revealing connections. Courtesy of the consortium of The Human Connectome Project

Phil Jaekl

is a writer with a scientific research background in cognitive neuroscience. He completed his PhD at York University in Toronto, and went on to research positions in Barcelona, Spain and Rochester, New York. His writing appears in The Atlantic, The Guardian and Wired, among others. His debut nonfiction book, Out Cold, about the history of using cold as a therapeutic tool, is available for pre-order. He lives in Tromsø, in Norway’s Arctic region.

3,800 words

Edited by Pam Weintraub

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In the Asturias region of northwest Spain, a cave drawing of a woolly mammoth has a single, internal feature: a large red heart. This work of art, at least 14,000 years old, likely depicts a successful hunt and bloody wound. From the earliest days of our species, the detection of a pulse, the preservation of respiration and the beating of a heart have served to separate a piece of meat from a living being.

The fundamental connection between breathing, heartbeat and life itself began to change as knowledge of the brain’s role in consciousness evolved and as technology made it possible to use machines to operate the heart and lungs while a patient remained on life support. Today, we define life and death by the presence or absence of brain activity. That makes sense because, unlike other organs, the brain not only signals life, but is essential to you, the individual, to your own unique qualities of identity, memory, knowledge and subjective experience of the world.

To better understand how the brain underlies selfhood, we need to understand its complex form; its intricate structure at the level of connections between neurons. After all, understanding biological structure has revealed the nature of many diverse life forms. Plants thrive because their typically broad leaves are perfect for transducing light energy into vital chemical energy. Similarly, eyes, whether human or insect, enable the transduction of light from one’s surroundings into electrical signals within the nervous system. These impulses carry information that represents features of the surrounding environment. But when it comes to the relationship between structure and function, brains have remained an enigma. There’s a lot more to them than to other organs that have specific functions, such as eyes, hearts or even hands. These organs can now be surgically replaced. Yet, even if a brain transplant were possible, you couldn’t just switch your brain with another person’s and maintain the same mind. Such an idea of brain replacement is a logical fallacy.

What is it about a brain that creates individual experience?

Upon birth, a person’s brain structure is largely prescribed by experience in the womb and their unique genetic code. As we age, experience continues to imprint unique changes on the brain’s neural connectivity, increasing connections in some areas while decreasing them in others, accumulating reroutes upon reroutes as a person ages and learns, gaining knowledge and experience. Additionally, there are alterations in the strength of existing connections. These processes are especially evident in twins, whose brains are strikingly similar when born. However, as they grow, learn and experience the world, their brains diverge, and their essential selves become increasingly unique.

Essentially, this process creates memory, something so fundamental that it unconsciously surfaces in every aspect of our sense of self. Even our unconscious knowledge of movements needed for riding a bike, speaking a word or even walking require memory. Incredibly, hypothermia victims, who have undergone hours of clinical death signified by an absence of both heart and brain activity can achieve a state of full recovery, demonstrating that neural electrical activity alone is not essential for the storage of memory in the brain.

Although there are indeed anatomical regions that appear to serve relatively specific functions, one’s memory is not formed, stored or recalled within the activity of any single brain region. Certain structures, such as the amygdala and the hippocampus, play key roles but trying to find memory in one specific area is simply impossible. It would be like trying to listen to Beethoven’s Fifth but hearing only the strings (duh duh duh, duuuh!). Instead, memory, in its broadest sense, lies in the uniqueness of a brain’s entire connective structure, known as the connectome. The connectome consists of its complete network of neurons and all the connections between them, called synapses. It is argued that, fundamentally, ‘you are your connectome’.

Thus, a key to unlocking the correspondence between the connectome and memory is to elucidate the entire circuitry of the brain. Tracing the wiring at this scale is no easy task when considering the sheer complexity involved. A mere cubic millimetre of brain tissue contains around 50,000 neurons, with an astonishing total of around 130 million synapses, according to some estimates. An entire human brain, however, is more than 1 million cubic millimetres and contains around 86 billion neurons, nearly equivalent with estimates of the number of stars in our galaxy.

The most relevant number is the one representing the total sum of synaptic connections, which comes in at a mind-numbing c100 trillion. Once the possible paths that electrical neural signals can run on across these connections are determined, only then might it be possible to comprehensively know the patterns of activity integral to memory and to subjective experience.

Obtaining connectomes could go a long way to answering some fundamental questions about the relation between neurons and behaviour. I asked Jeff Lichtman, a neuroscientist at Harvard University and a pioneering connectomicist, what we could do with a human connectome, should we be able to reproduce it, and he said the benefit would be profound. We could, for instance, come up with far more effective therapies for neurocognitive disorders such as schizophrenia or autism – problems thought to be caused by miswiring – though we still aren’t sure how.

Lichtman’s research has been inspired by the insight that, across species, the brain’s wiring diagram changes as individuals grow and develop through life. But his greatest motivation is charting the unknown reaches of the mind imprinted in the connectome data itself. He compared the connectome, in this respect, to genomics. Having a full human connectome, he noted, would be analogous to a full genome – opening a universe of discovery we can’t even fathom right now.

But simpler models of connectomes from other species have already helped science advance. Researchers at the Allen Institute for Brain Science in the US, for instance, have traced the circuitry of an entire mouse brain, showing how different types of neurons connect various anatomical regions. A collaboration at the Janelia Research Campus, involving Google scientists and centred at the Howard Hughes Medical Institute in Ashburn, Virginia, mapped a large, central region of the fruit-fly connectome at the level of individual neurons; a feat that took more than 12 years and at least $40 million.

It’s crucial that the extracted brain is preserved accurately to maintain its complex connectome before it’s sliced up

Even before these remarkable accomplishments, pioneering researchers mapped the complete connectome of the roundworm, Caenorhabditis elegans, back in the 1980s – all of its 302 neurons and around 7,600 synapses – fuelling research for years. Complex simulations of activity on the roundworm connectome are revealing the synchronised activity patterns underlying its wriggling movements.

Across species, synchronisation and coordination of neural signals between seemingly distant brain regions within a connectome provide the scaffold for execution and memory of ordered sequences of events. For example, when young birds learn their songs, they encode, store and retrieve the sound patterns they hear from other birds, in various chains of neurons which, in turn, activate sequences of muscle movements that create the same sonic patterns. Currently there are at least 20 ongoing studies investigating relations between the human connectome and its role in memory, many coordinated by an organisation called the Connectome Coordination Facility of the US National Institutes of Health.

Mapping a connectome at the level of single neurons, however, is currently impossible in a living animal. Instead, animal brains must be extracted, perfused with a fixative such as formaldehyde and sliced up as many times as possible before being analysed structurally in order to painstakingly find individual neurons and trace their paths. To achieve this, the properties of each new slice are recorded using various microscopy techniques. Once that’s been done, patterns of electrical flow can be estimated from different neuron types and from connections that excite or inhibit other neurons. What’s crucial is that the extracted brain is preserved accurately enough to maintain its intricate, complex connectome before it’s sliced up.

Currently, it’s unlikely that any human brain has been preserved with its entire connectome perfectly intact. Our brains degrade too quickly after death. Without oxygen-rich blood flow, there’s a marked drop in metabolic activity, the set of chemical reactions that maintains an organism’s cellular life. When the brain’s cells stop metabolising, irreversible structural damage from a lack of fresh oxygen can begin within just five minutes. Slicing up a brain for connectome mapping thus requires preserving it as soon as possible to minimise this damage.

And so, to actually maintain the exact structure of the entire connectome, you need a preservation method where every single neuron and each of its synaptic connections are held in place – a requirement that must succeed about 100 trillion times over, for an individual human.

The implications surrounding a human brain-preservation technique that can keep the entire connectome intact are profound. If indeed, you are your connectome, defined by all the memories and essences of you imprinted in its structure, then it’s essentially you that’s preserved. Your connectomic self.

Theoretically, the logic suggests the prospect of escaping death.

In 2010, a group of neuroscientists came together over shared interest in this idea, actualising their motivations by creating the Brain Preservation Foundation (BPF). The president and co-founder of the BPF is Ken Hayworth, also a senior scientist at the Janelia Research Campus. Over the phone, he told me that he hoped to involve scientists in making brain preservation an option for patients with terminal illness. ‘I know someone in a hospital who is dying and there is simply no option for them now,’ he said. ‘If nobody advocates for this procedure, surely it will never happen … I will want this option when it is my time to face a terminal illness.’

Soon after forming, the BPF began offering a $100,000 cash prize, donated by the Israeli tech entrepreneur and poker player Saar Wilf, for new methods of connectome preservation. The competition was structured in two stages based on increasing brain size: a small-mammal prize and a large-mammal prize. With a set of detailed evaluation guidelines involving molecule-level electron microscopy scans, the challenge was put forth to anyone willing to undertake the enormous effort involved.

And who best to undertake the challenge than the cryonics community, devoted to cryopreserving terminally ill people (or just their brains) right after death, in hopes that they will be thawed after storage in liquid nitrogen in a future that has a cure. Hayworth wanted the prize money to prompt them to demonstrate the effectiveness of their preservation techniques. He told me: ‘The prize was meant to motivate the cryonics providers to “put up or shut up”.’

But by 2018, cryonics still hadn’t put up. Instead, scientists from a private cryobiological research company in California, 21CM (for 21st-Century Medicine), focused on preserving frozen specimens, won both stages, claiming the preservation prize after demonstrating intact connectomes in a preserved rabbit brain and subsequently in a preserved pig brain. Greg Fahy, 21CM’s founder and an experienced cryobiologist, innovated the prizewinning technique along with Robert McIntyre, a graduate of the Massachusetts Institute of Technology (MIT). The process, technically called aldehyde-stabilised cryopreservation, but now branded vitrifixation, hinges on using a fast-acting fixative called glutaraldehyde, previously used as a disinfectant, in combination with other chemicals that cause the brain to enter a vitrified physical state, hence the name, vitrifixation.

He wondered if he could somehow extract a memory from a brain – essentially a ‘living memory’

The process spelled a revolution for futurists because the connectomes were deemed intact after cryogenic freezing down to at least -135°C. At this temperature, all metabolic, biological processes cease to the point of enabling indefinite storage, potentially for hundreds, if not thousands of years, with no sign of rotting. Assuming the relevant logic regarding the connectomic self and the role of memory is correct, vitrifixation can essentially enable the preservation of you, indefinitely, in a form of suspended animation.

McIntyre has long held that there’s great value in preserving not just the physical brain structures but memory itself, held within those structures. After all, human progress depends on the transference of information over time, via great leaps of innovation. The first such leap was achieved upon the establishment of oral language and the next upon written language, which could more accurately preserve information, possibly for longer stretches of time. ‘Could you imagine going back in time and telling someone, in a time before written language, that one day it will be possible to turn anything they can speak into carvings in stone that can last aeons, for anyone in the distant future to discover? They wouldn’t have believed you,’ McIntyre told me over the phone.

He was first inspired by the prospect of using neuroscience to extract memories from brains, because they contain far more information about experiences and events than any other current form of preservation, such as writing, audio or even video. After listening to recordings of his grandmother talking about travelling by covered wagon from Oklahoma to Texas, among other historic life experiences, he wondered if it could be possible to somehow extract a memory from a brain – essentially a ‘living memory’, the first-hand perspective of actually being there – the information you’re missing after you read, for example, a history textbook, as compared with personally having lived through that same history yourself.

As a student, he visited a neuroscience lab, where researchers called the idea outlandish and impossible to achieve. Instead, he decided to approach the problem computationally, by using artificial intelligence (AI) to solve it. He completed coursework at MIT, and in 2014 accompanied his father to a cabin in the wilderness to finish the dissertation for his PhD. The two of them took a walk that changed his life. While toting handguns in case of rattlesnake attack, his father asked him, aside from AI, how he might salvage memory directly. They concluded that the best way was to leave it up to the future to create technologies that are largely unimaginable to us now, while preserving the substrate of those memories, the connectome itself.

If connectomes hold memories that can be re-experienced, their importance is unique. Take the wisdom achieved by soldiers after experiencing life-changing events during a war. It’s one thing to read about world wars in textbooks or even in personal memoirs, but those forms of information don’t directly carry the detail contained in a living memory of experiencing war firsthand. It’s a deep sort of wisdom, McIntyre believes, that could enrich humanity with the knowledge, foresight and judgment needed to divert it from an unsustainable, species-ending path.

Now, through vitrifixation, there was finally a technique for immortalising memories in the connectome that BPF scientists could advocate. Unfortunately, the fixative agent used to perfuse the vascular system in vitrifixation is entirely and directly fatal. You couldn’t immortalise memories without killing their creator.

If you were to go through the procedure, after experiencing your last thought, a general anaesthetic will be used to subdue you. Then, your chest will be opened and your arteries connected to a perfusion apparatus. After being exsanguinated and pumped with glutaraldehyde, it will diffuse into your brain’s capillaries and cease all metabolic activity, killing you nearly instantly while connecting proteins constitute your brain into a robust, lasting meshwork. Afterwards, your brain will be perfused with antifreeze to prevent damage before it’s extracted and cryogenically stored indefinitely.

To make a terrible pun, it seems like a no-brainer. The treatment (death) is worse than the problem: living memory lost. Yet both Hayworth and McIntyre believe that vitrifixation, though fatal, offers a type of immortality, if the essence of someone can be scanned for all the relevant information and then somehow transferred to an artificial medium; one that essentially replaces the brain, from a functional standpoint. Crucially, this medium, when ‘running’ would have to accurately and sufficiently conduct the patterns of neural activity that support one’s memory, identity and experience to evoke their unique consciousness.

This goal is called ‘whole-brain emulation’. After all, why do brains have to consist of only biological material? And if minds can run on a network of connections, can’t they be ‘substrate independent’ such that all the information essential to a mind is contained in the arrangement and operation of those connections, not any given substrate itself?

Although the relevant science is in its infancy, some significant achievements exist. Many approaches foresee computational mediums for emulating brain activity involving digital information spaces. Currently, brain-computer interfaces enable thought-controlled activity of prosthetic machines. Moreover, actual neural prosthetics are directly replacing brain cells. It’s form to function in the truest sense. What’s more is that multimillion-dollar tech enterprises such as Neuralink, Kernel, Building 8 and DARPA are forging even more advanced connections between mind, brain and computer that increase the possibility of such whole-brain emulation.

We must ask if we’re consigned to exist as the very molecules that presently constitute ourselves?

So how exactly would you emulate something as astronomically complex as a brain? Two approaches have gained traction. The first, and most popular, involves creating a digital simulation of the connectome and its activity, perhaps at a molecular scale, and then setting it free in cyberspace. In this grandiose scheme, the simulation is so complete and accurate that it becomes an emulation with the emergent property of a person’s identity, memory, consciousness, thoughts and feelings in the same way that we currently understand subjective experience to be an emergent property of someone’s active biological brain. As it’s been construed, this future involves the possibility of living in a virtual, simulated world where you mingle with other emulated minds. The second approach involves transplanting the emulated brain into a prosthetic self, the ultimate cyborg in which every part of you is synthetic. In this case, your mind could exist in the real world with a completely artificial body.

But perhaps you would go no further in survival than your lifeless, vitrifixed brain and whatever might remain of the rest of your corpse. In either scenario, even if the ‘new you’ were to be a complete, conscious emulation with the same memories, identity, feelings and subjective self, there remains the striking possibility that it wouldn’t actually be you. Rather, a doppelgänger: a duplicate, identical in all respects. After all, it should be just as possible to create multiple instances of a new you; then, which would be you? All? In this way, memories, identity and conscious subjective experience is like a song that can be played on any instrument that can produce its neural notes.

Alternatively, definitions of personal identity and survival could come to surround you as a continuous property, rather than as a binary, yes/no alternative. When you’re old, you’re essentially only partially the same person as you were when you were born, but at no point in the transition does the younger you die while the old you is suddenly created. Essentially, we must ask whether we are consigned to exist as the very molecules that presently constitute ourselves? As we explore consciousness and connectomes, our ways of thinking about them could evolve by great leaps. In my conversations with Lichtman, Hayworth and McIntyre, I heard a similar message: although the possibility of reanimation is the current beachhead, by the time we can achieve it, human knowledge, culture and technology are likely to alter the form it takes.

When I probed McIntyre on this, he simply said: ‘If brains can do it [eg, revive after clinical death in survivors of cardiac arrest], we can do it – and we’ll figure out how.’ Like Lichtman (who considers himself a ‘presentist’ rather than a futurist), McIntyre made an analogy with the discovery of DNA. ‘When it was discovered 70 years ago, nobody really knew what to actually do with it, and now…’ Hayworth adds: ‘This is really not happening any time soon.’ But also: ‘humanity will eventually succeed in understanding the brain, and in developing the scanning and simulation technologies that are needed … humanity will eventually figure it out.’

With such far-reaching prospects comes great responsibility. Vitrifixation’s potential for escaping death entails numerous ethical questions that remain unanswered, despite formal consideration: would there be equal opportunity to engage the process or would it be exclusive to those who can afford it, for example? How would one’s memories be safeguarded against tampering, destruction or theft? Who would have ownership? Under what circumstances could memories in a virtual connectome be accessed, and by whom?

One issue seems less fraught: the potential for making vitrifixation an option for terminally ill patients as soon as it can be achieved.

Taking on all this, McIntyre and his former roommate at MIT Michael McCanna founded a controversial venture capital startup after winning the $100,000 prize. Their company is a brain bank initiative called Nectome. Its primary goal, as stated on the company’s website, is to preserve and essentially archive human memory. So far, Nectome has raised more than $1 million in funding and has received a $960,000 federal grant from the US National Institute of Mental Health for ‘whole-brain nanoscale preservation and imaging’. The federal grant explicitly mentions the possibility of a ‘commercial opportunity in offering brain preservation’.

Undergoing vitrifixation could amount to nothing more than suicide at a considerable financial cost

Nectome already has a list of at least 30 supporters, each having given a $10,000 donation. The process, which has never actually been performed on a living human, is technically legal in five US states under current physician-assisted suicide laws for those who are terminally ill. Nectome’s only human vitrifixation, in fact, was performed on the brain of an elderly woman whose corpse was given to McIntyre by the body-donation company Aeternitas Life. The operation was performed just 2.5 hours after the woman’s death, resulting in one of the best-preserved brains in existence.

It’s no surprise that Nectome has seen some serious controversy. The donations are incorrectly construed in various media reports as ‘deposits’ for suicidal procedures, something that McIntyre denies outright. ‘Those donors wanted to become early supporters. We don’t offer any brain preservation service,’ he told me when I asked. But responding to the uproar, MIT ended an ongoing neuroscience collaboration with the company in 2018.

The sobering fact of the matter is that anyone hoping to become a Nectome client might very well have a futile wait. The claim that the self can be found in the connectome is still a long way from being proven, and there might never be any way to determine if consciousness can exist in a machine. Undergoing vitrifixation could amount to nothing more than suicide at a considerable financial cost.

No one should be rushing out to get their brains preserved when there’s no guarantee that it will work, Hayworth states. Instead, he says he just wants to further the science. ‘It might not work, obviously, but people are dying. [Vitrifixation] is already proven to reliably preserve precisely those structures and molecules that modern neuroscience says encode us. Therefore, terminal patients should have the opportunity to take that chance, if they wish.’

From the current views of Lichtman to the futurist optimism actualised by Hayworth and McIntyre, one sentiment is consistent: the connectome has the potential to immensely impact our future in unknown, but meaningful ways.

Phil Jaekl

is a writer with a scientific research background in cognitive neuroscience. He completed his PhD at York University in Toronto, and went on to research positions in Barcelona, Spain and Rochester, New York. His writing appears in The Atlantic, The Guardian and Wired, among others. His debut nonfiction book, Out Cold, about the history of using cold as a therapeutic tool, is available for pre-order. He lives in Tromsø, in Norway’s Arctic region.

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