Major leap towards reanimation after death as mammal's brain preserved

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

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

When it comes to preserving the minute architecture of the brain, timing is critical. Within minutes of blood no longer circulating, enzymes break down neurons and cells start digesting themselves.

Cryonics usually involves preserving people’s bodies at sub-zero temperatures in the hope that they could 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 occurs.

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

Wróbel’s team tested the protocol on pigs, which have brain and cardiovascular anatomy that is comparable to people. First, they inserted a cannula into the heart roughly 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 within tissue, preventing the formation of ice crystals during cooling, which would otherwise damage cells. Next, the brain was 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 brain’s outermost layer and examined them using microscopy. Early attempts, in which perfusion began around 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 minute structures, including neurons, synapses and the molecules that compose them.

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 out, it might help us understand how the brain produces our thoughts, feelings and perceptions. So far, scientists 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, “reanimation” isn’t yet an option. “The approach is essentially a form of fixation using toxic chemicals that preserves the structure of the brain and neurons, but without expectation of biological viability,” says Joao Pedro de Magalhaes at the University of Birmingham, UK. “There is currently no way to revive an organ preserved in this way, as it is a sort of embalming.”

De Magalhaes also isn’t convinced that a person could “live on” by reconstructing their connectome. “Even a perfect copy of my mind would still be a different entity, although I appreciate that some people see this as a potential path to a sort of ‘virtual immortality,’” he says.

Nevertheless, Wróbel’s team thinks the human mind could one day be recreated, digitally or biologically. “Although we’re agnostic towards the type of revival methods, we think 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 family, before taking part in the new protocol. “They would come to us, take the medication – which would have to be prescribed by an independent doctor, not us – and then, after it is legal to do so, we would start the surgery,” says Wróbel.

Regardless of hypothetical futures, the work raises profound philosophical questions about our definition of death. “It’s long been known that declaration of death based on stopped blood circulation is a formalised prognosis of futility, not a metaphysical event,” says Brian Wowk at biotechnology company 21st Century Medicine in Fontana, California.

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