Written by Sean Green

Edited by Andrew Neff

June 2019

A 21st Century Frankenstein

The neuroscience of reviving brains

Science fiction has blurred the line between life and death since Mary Shelley wrote Frankenstein over two centuries ago. Modern sci-fi and fantasy in television shows such as Altered Carbon, The Walking Dead, and Game of Thrones carry on that tradition. Shelley's work reflected the cutting-edge science of the day: inducing cadavers to move through electrical stimulation [See 1]. Recently, a study by Vrselja and colleagues [2] at the Yale School of Medicine showed that science continues to blur that line. These researchers preserved crucial elements of brain function in pig brains four hours after the pigs' deaths.

 

One persistent challenge for doctors and neuroscientists is that mammal brains that have lost their oxygen supply do not always react well when oxygen returns. Damage, called reperfusion injury, can occur. Typically, the brain is at risk for permanent damage after only a few minutes without oxygen. Even when patients do recover from oxygen deprivation, recovery may not be permanent. Weeks after recovery, their brain functions may still deteriorate. Clearly, bringing someone back isn't as simple as flicking an on/off switch. 

 

There are exceptions to this rule. If body temperature drops, for instance in someone who has fallen into icy water, they can sometimes recover after up to 6 hours. A recent review of these cases states in its title, “Nobody is dead until warm and dead.” This led researchers like Vrselja to look for other ways besides hypothermia to protect the brain during reperfusion. 

 

Vrselja and colleagues discovered a way to protect “warm and dead” brains, using a process called BrainEx [2]. BrainEx uses a computer-controlled pump to deliver a solution to the brain. This solution contained cytoprotective (cell-protecting) chemicals and energy sources. The researchers found that after six hours of the process, BrainEx brains did not show the signs of damage that typically would result from hypoxia. The brains did not show swelling or dry out. Support cells called glia functioned the way they were supposed to. Neurons in the hippocampus responded appropriately to signals. This last point is particularly important because the hippocampus helps the brain to learn and form memories.


Vrselja's team took pains to prevent the pig brains from achieving normal brain activity. Their aim was to keep the cells alive and restore normal circulation, not to revive the animals. This study cannot determine whether BrainEx could restore consciousness or awareness. Still, it raises the intriguing but troubling question: what happens if somebody else uses the same technology to push farther, resuscitating a human and allowing their patient to emerge from anesthesia?

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The technology could save lives. First responders would have greater latitude to treat patients, especially during mass casualty events. Patients on transplant lists might be able to take their brain “offline” until a match is available. Technicians could preserve the brain while doctors healed the body, allowing the brain to “reboot” once the body was ready for it. Consider how other technologies – antibiotics, antivirals, vaccines, heart-lung machines, and many others – turned death sentences into reprieves. Today, as in Mary Shelley's time, people often turn to faith for reassurance that death is only temporary. Techniques like BrainEx could be the first step towards a scientific fulfillment of that promise.

 

When science attempts to work miracles, the results can be imperfect, which raises questions for doctors and patients alike. What if recovery is incomplete? Game of Thrones shows in horrifying detail the consequences of reanimating a body without retaining the mind. If this technology – still in its infancy – changes the brain in ways we cannot predict, it might become a curse rather than a reprieve. Equally troubling, what if the treatment is expensive or insurance companies do not cover it? We would face a world where the poor, but not the rich, face the fear of death.

 

Like Prometheus's fire and Aldini's electricity, forces unleashed in the twenty-first century have the power to stave off death, but also to transform society in wondrous and dangerous ways.

References

[1] Parent, A. (2004). Giovanni Aldini: from animal electricity to human brain stimulation. Canadian Journal of Neurological Sciences, 31(4), 576-584. 

[2] Vrselja, Z., Daniele, S. G., Silbereis, J., Talpo, F., Morozov, Y. M., Sousa, A. M., ... & Zhuang, Z. W. (2019). Restoration of brain circulation and cellular functions hours post-mortem. Nature, 568(7752), 336.  

[3] Hilmo, J., Naesheim, T., & Gilbert, M. (2014). “Nobody is dead until warm and dead”: Prolonged resuscitation is warranted in arrested hypothermic victims also in remote areas–A retrospective study from northern Norway. Resuscitation, 85(9), 1204-1211. 

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