The Science of Life and Death

If we freeze our brains, could future technology bring us back to life? The study of neural connections may answer that question. 

By Sebastian Seung|Saturday, September 01, 2012
Tom Wang/Shutterstock

The headquarters of the Alcor Life Extension Foundation are in a strange industrial building in Scottsdale, Arizona. If you were to enter a restricted area of the building, you would see rows of metallic containers, each about 10 feet tall. The containers are called dewars, and like giant thermos bottles, they insulate their contents, using liquid nitrogen instead of ice cubes. Each contains either four human corpses together with 10 human heads, or up to 45 human heads only.

The foundation has about 975 living members and 114 dead ones. You can join the club by guaranteeing a $200,000 payment, to be handed over when you are pronounced legally dead. In return, the foundation promises to preserve your body indefinitely at 320 degrees below zero Fahrenheit. You can opt to preserve only your head, in which case the price drops to $80,000. The foundation has its own language. The people inside the dewars are not dead; they are “deanimated.” The frozen heads are neuropreservations, and the practice is called cryonics.

Alcor members are optimists. They hope that in the long run, advances in science and technology will eventually enable humans to reanimate dead bodies. Not only will the frozen corpses in the Alcor warehouse be brought back to life, but their diseases and old age will be reversed. The reanimated will be restored to their youthful vigor.

The physicist Robert Ettinger was the first to bring the idea of cryonics before the attention of the public with his best-selling 1967 book, The Prospect of Immortality. All the same, it took several false starts before cryonics became a reality. In the early years there were some embarrassing episodes in which frozen bodies accidentally thawed and had to be buried just like the corpses of other dead people. Finally, in 1993, the Alcor Life Extension Foundation created the facility in Scottsdale, which seems secure enough to keep bodies frozen for many years.

It’s tempting to dismiss Alcor members as suckers who have been fleeced of large sums of money. But this reaction would be too hasty. Can anyone really prove that reanimation will always be impossible? It seems more reasonable to say that the probability of reanimation is small but nonzero.

If the body is a machine, why can’t it be repaired? That possibility doesn’t seem to violate the laws of logic or physics, assuming that you accept the concept of mechanism. That’s the philosophical doctrine that the body—and therefore the brain—is nothing more than a machine. Granted, our bodies are much more sophisticated than the machines we make, but in the end, mechanism says, there is no fundamental difference.

Optimistic though we may be about future advances, there’s a fundamental limitation: The brain is an organ that cannot be replaced, unlike any other body part. That is not a statement about the technical difficulty of a brain transplant. What I am talking about is the issue of personal identity, illustrated nicely by the true story of Sonny and Terry.

In 1995 Sonny Graham received a heart donated by Terry Cottle, who had committed suicide. In a surprising turn of events, Terry’s widow, Cheryl, married Sonny nine years later. Four years into their marriage, Sonny, too, committed suicide, shooting himself in the throat. Newspapers went crazy with headlines like “Suicide Claims Two Men Who Shared One Heart.” Did the transplanted heart contain memories that made Sonny fall in love with Cheryl? No. Clearly, after receiving Terry’s heart, Sonny was still Sonny. His personal identity remained intact. It’s doubtful that it was the transplanted heart that made him fall in love with Cheryl.

In contrast, let’s consider a hypothetical brain transplant. Suppose Terry’s brain had been transplanted into Sonny’s body. It would not make sense to say that Sonny had received Terry’s brain, since the postsurgical Sonny would not be the Sonny his friends knew. In other words, we could call it a body transplant rather than a brain transplant. Then Cheryl’s second encounter with a suicidal
husband might have a different explanation.

The bizarre story of Sonny and Terry introduces an important point for cryonics: Preservation of the brain is the pivotal issue. Will a future civilization be able to revive frozen brains? I think this question is profoundly interesting even for those who don’t care a whit about Alcor. Reanimation is the ultimate challenge for the doctrine of mechanism. Philosophers can argue until they’re blue in the face, and scientists can uncover all the evidence they want, but they can never completely convince us that the body and the brain are machines. The final proof will come only when engineers manage to construct machines that are just as complex and miraculous as bodies—or when they can bring dead bodies and brains back to life by repairing them.

What are the fundamental limits of restoring life to damaged brains? We cannot properly address this question without considering the connectome.

A nervous system is an assembly of neurons, wired together by the slender branches called neurites, which include both axons and dendrites. We say that two neurons are connected if there is a small junction, called a synapse, at a point where the neurons touch. A connectome is the totality of connections between the neurons in a nervous system. The term, like genome, implies completeness. A connectome is not one connection, or even many. It is all of them. In principle, your brain could be summarized by a diagram that mapped these connections. What would your connectome reveal about you? First, it would reveal that you are unique. You know this, of course, but it has been surprisingly difficult to pinpoint where your uniqueness resides. Your connectome and mine are very different.

I propose a simple theory: Minds differ because connectomes differ. Personality and IQ might also be explained by connectomes. Perhaps even your memories, the most idiosyncratic aspect of your personal identity, could be encoded in your connectome. In short, you are your connectome.

The Slow Freeze

Alcor’s procedures are based on a field of science known as cryobiology, the techniques used to freeze sperm, eggs, and embryos for later use. The classic method is to lower the temperature slowly, say one degree per minute, after immersing cells in glycerol or other cryoprotective agents.

Slow freezing was discovered mainly by trial and error. To improve on the method, cryobiologists have tried to understand why it works. It’s not easy to sort out the complex phenomena happening inside cells during cooling, but one thing is certain: The formation of ice inside cells is lethal. It’s not known why intracellular ice kills, but cryobiologists know to avoid it at all costs.

Slow freezing is intended to cool cells so that the water outside freezes to ice while the water inside does not. How is that possible? The higher the concentration of salt, the lower the freezing point. When cells are cooled slowly, water is gradually sucked out of them owing to a force known as osmotic pressure. The water remaining in the cell becomes saltier and saltier, and hence resists icing.

This freezing is not completely benign, because it prevents ice with saltiness, and additives like glycerol can protect only so much. The method is far from perfect. Sperm survive the best; eggs and embryos do less well. Some researchers have therefore given up on slow freezing. Instead, they cool cells under special conditions that turn liquid water into an exotic state of matter that is said to be glassy or “vitrified,” from the Latin word for glass. The vitrified state is solid but not crystalline. Its water molecules remain disorganized; they’re not arranged into the orderly lattice you see in ice crystals.

Under normal circumstances, vitrification requires extremely rapid cooling, which is feasible for cells but not entire organs. Alternatively, you can get water to vitrify even at slow cooling rates if you add extremely high concentrations of cryoprotectants. Fertility researchers are already applying this method to oocytes (immature eggs) and embryos, with some success. Over the years, vitrified organs failed the acid test repeatedly: They didn’t survive and function after rewarming and transplantation. In a remarkable advance, one team has at last succeeded, demonstrating recently that a previously vitrified kidney functioned for weeks after transplantation into a rabbit. Inspired by this research, Alcor now uses vitrification to preserve the corpses of its members.

There’s a more fundamental problem than freezing, though. The Alcor members were all dead before they were vitrified, for hours or sometimes even days. Isn’t death irreversible? If so, how could reanimation ever succeed?

But “irreversible” depends on currently available technology. For most of human history, a person was dead when respiration and heartbeat stopped. Now such changes are sometimes reversible. It is now possible to restore breathing, restart the heartbeat, or even transplant a healthy heart to replace a defective one. What is irreversible today might become reversible in the future.

These thought experiments should motivate us to find a definition of death that is more fundamental. Ideally, the definition should remain valid no matter how far medicine progresses in the future. If my hypothesis that “you are your connectome” is true, a fundamental definition of death follows: Death is the destruction of the connectome.

Of course, we don’t know yet whether a connectome contains a person’s memories, personality, or intellect. It might not contain all the information. Some of the information in a person’s memories might be lost even if the connectome is perfectly preserved.

Reversing the Damage

Could the damage done to the brains of Alcor members be reversed in the future? To find out, I propose that we attempt to find the connectome of a vitrified brain, using connectomics to critically examine the claims of cryonics.

We can only speculate about what this test might find. It’s well known that the brain is extremely sensitive to oxygen deprivation. Loss of consciousness follows in seconds, permanent brain damage after a few minutes. At first glance, this seems like bad news for Alcor members. By the time Alcor receives the corpse, the brain has been deprived of oxygen for hours at least, and no living cells may remain. (Of course, it can be as difficult to define life and death for a cell as for the whole body.)

Whether dead or alive, the cells have been badly damaged. Electron microscope studies have characterized the types of damage present in brain tissue a few hours after respiratory/circulatory death. Among other changes, mitochondria look damaged, and the DNA in the nucleus is abnormally clumped.

But these and other cellular abnormalities are irrelevant for connectome death. What matters is the integrity of synapses and “wires.” Synapses are still intact in the electron microscope images, so they appear to be stable even in a dead brain. The status of axons and dendrites is harder to judge. Their cross sections look largely intact in the published two-dimensional images, but there are some damaged locations.

The big question is whether the damage has actually broken the wires of the brain. This can be answered by attempting to trace the neurites in three-dimensional images. If there are few breaks, tracing might still be possible. One could deal with an isolated break by bridging the gap between two free ends that were obviously once joined. But if there are clusters of many adjacent breaks, it might be impossible to figure out which free ends were once joined together. This would be true connectome death, a loss of information about connectivity that can never be recovered, no matter how advanced the technology.

If the information in the connectome turns out to be erased, then we can declare connectome death. Resurrection by an advanced civilization of the future might be still possible, but only for the body, not for the mind. If, however, the information is intact, then we cannot rule out the possibility of resurrecting memories and restoring personal identity.

I suppose we should not conduct this experiment on a vitrified human brain. But Alcor has also vitrified the brains of some dogs and cats, at the request of pet-loving members. Perhaps some of these members would be willing to sacrifice their pets’ brains in the name of science.

It could turn out that the Alcor members stored in liquid nitrogen are already connectome-dead. If so, that would not be the end of Alcor. They could always use connectomics as a means to improve their methods of preparing and vitrifying brains. Short of actually resurrecting their members, this is the only way I can imagine assessing the quality of their procedures. Even if their current method does not prevent connectome death, they could ultimately find one that does.

[This article originally appeared in print as "The Science of Life and Death."]

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