Great leap towards resuscitation after death as the mammalian brain is preserved

An entire mammalian brain has been preserved using a technique that will now be offered to terminally ill people. The purpose is to preserve all the neural information deemed necessary to one day reconstruct the mind of the person it once belonged to.

“They would need to donate their brains and bodies for scientific research,” says Borys Wróbel of Nectome in San Francisco, California, a research company focused on memory preservation. “But what we’re offering, as a company, is for their body and their brain to be kept, essentially indefinitely, in the hope that at some point in the future it would be possible to read out the information from the brain and reconstruct the person … to allow them to go on, in fact, with life.”

When it comes to preserving the brain’s smallest architecture, timing is essential. Within minutes of the blood no longer circulating, enzymes break down neurons and cells begin to digest themselves.

Cryonics usually involves preserving people’s bodies at freezing temperatures in the hope that they may one day be revived if a treatment or cure for their medical condition becomes available. Traditionally, this aims to preserve the brain quickly after natural death by cooling it and adding fixatives, but unless the cryonics team is at a person’s bedside, deterioration will have already begun before this happens.

To circumvent this problem, Wróbel and his team have developed a protocol compatible with physician-assisted death, in which a terminally ill person chooses the time of death. The idea is that by intervening immediately, researchers may have the best chance of preserving the brain in a state that closely mirrors a living condition.

Wróbel’s team tested the protocol on pigs, which have brain and cardiovascular anatomy comparable to humans. First, they inserted a cannula into the heart about 1 minute after cardiac arrest, before flushing out the blood and introducing preservation solutions into the brain. These fluids contain aldehyde chemicals, which create molecular bridges between cells, essentially locking cellular activity in place.

They then introduce cryoprotectants, which replace water in tissues and prevent the formation of ice crystals during cooling, which would otherwise damage the cells. The brain was then cooled to around -32 °C, at which temperature cryoprotectants form a glass-like state. The structure of the brain can then be preserved indefinitely.

To assess how well this worked, the team took samples from the outermost layers of the brain and examined them using microscopy. Early experiments, in which perfusion began about 18 minutes after death, showed clear signs of cellular damage. After reducing this delay to just under 14 minutes, the tissue showed excellent preservation of the small structures, including neurons, synapses and the molecules that make them up.

Wróbel says that in theory they could use this protocol “to reconstruct the three-dimensional structure of the neurons and the connections between them”. This is known as the connectome, and it is hoped that by mapping it, it can help us understand how the brain produces our thoughts, feelings and perceptions. So far, researchers have managed to map only a small part of the mouse brain in this way, which took seven years to complete.

Despite advances in both cryopreservation and computing, “resuscitation” is not yet an option. “The approach is essentially a form of fixation using toxic chemicals that preserve the structure of the brain and neurons, but without the expectation of biological viability,” says Joao Pedro de Magalhaes of the University of Birmingham, UK. “There is currently no way to revive an organ preserved in this way, as it is a form of embalming.”

De Magalhaes is also not convinced that a person can “live on” by reconstructing their connection. “Even a perfect replica of my mind would still be another entity, although I appreciate that some people see this as a potential path to some sort of ‘virtual immortality,'” he says.

Nevertheless, Wróbel’s team believes that the human mind can one day be recreated, digitally or biologically. “Although we are agnostic about those kinds of revival methods, we believe we may be able to preserve all the information needed for revival,” says Wróbel.

He says the team at Nectome is preparing to invite people with a terminal illness to Oregon, where they can spend a few days with their families, before taking part in the new protocol. “They would come to us, take the medicine – which had to be prescribed by an independent doctor, not us – and then, after it is legal to do so, we would start the operation,” says Wróbel.

Regardless of the hypothetical future, the work raises profound philosophical questions about our definition of death. “It has long been known that death by circulatory arrest is a formalized prognosis of futility, not a metaphysical event,” says Brian Wowk of the biotechnology company 21st Century Medicine in Fontana, California.

“The ability to preserve the detailed structural and molecular makeup of a brain, perhaps even preserving what makes a person who they are at the most basic level—even after significant periods of stopped blood circulation, as this study does—underscores that the difference between life and death is more complicated than just the cessation of vital functions,” he says.