Posted on Apr 18, 2019, 4 p.m.
Four hours after being killed in a slaughterhouse, Yale University scientists have partially revived function of dead pig brains; none of the brain functions regained were the kind of organized electrical activity associated with awareness of consciousness, as published in the journal Nature.
News of a surprising amount of cellular function being either preserved or restored in the dead animal brains has brought forth implications that have ethicists debating as to how far this research should be allowed to more forward, and to how it fits into current understandings of what separates the living from the dead. Despite the controversy findings could lead to major medical advances such as better therapies for stroke and disorders that cause brain cells to die.
Nita Farahany of Duke Law School says, "It was mind blowing. My initial reaction was pretty shocked. It's a groundbreaking discovery, but it also really fundamentally changes a lot of what the existing beliefs are in neuroscience about the irreversible loss of brain function once there is deprivation of oxygen to the brain."
Even though the brain is highly sensitive to lack of oxygen and it will shut down quickly, researchers know that viable cells can be removed post mortem hours after death to be studied in lab dishes, says Nenad Sestan, "but the problem is, once you do that, you are losing the 3D organization of the brain."
The team has spent the past 6 years developing a technique to study brains cells while leaving the organ intact, testing methods on around 300 pig heads obtained from a local pork processing center, having no preconceived notions of whether it would work or not; their goal was not to restore consciousness, rather some function.
After deciding on the final version of BrainEx technology a detailed study was conducted using 32 pig heads that were flushed out at the slaughterhouse to clear residual blood and cool down tissues. Once at the lab the brains were removed from the heads to be placed in an experimental chamber then key blood vessels were hooked up to a device that pumps a specially formulated chemicals into the isolated brain for 6 hours, which began around 4 hours after the animals had been slaughtered.
These brain looked dramatically different than brains that were left alone to deteriorate Sestan explains, "We found that tissue and cellular structure is preserved and cell death is reduced. In addition, some molecular and cellular functions were restored. This is not a living brain, but it is a cellularly active brain."
This could lead to new ways to study brain disease or injuries and to explore basic biology of the brain to possibly answer some important questions that have yet to be answered. Andrea Beckel-Mitchener of the National Institute of Mental Health agrees, "This is a real breakthrough for brain research. It's a new tool that bridges the gap between basic neuroscience and clinical research."
The chemical cocktails pumped into the brains includes the drug lamotrigine known to block or dampen neuronal activity, and brain electrical activity was constantly monitored for evidence or signals associated with consciousness, had any emerged they brains would have been anesthetized and cooled to shut it down immediately.
Stephen Latham, Yale bioethicist explains, “... the reason is that they didn't want to do an experiment that raises the ethical questions that would be raised if consciousness were being evoked in this brain, without first getting some kind of serious ethical guidance..."
Testing on single cells that involved washing off the chemical cocktail shows the individual cells were capable of electrochemical responses, however it is unclear if global activity linked to consciousness in the brains would have been seen if the neuronal activity blocker had been left out or had been removed after the cells had partly revived. According to Stefano Daniele, "We cannot speak with any scientific certainty to that point since we did not run those experiments."
This study raises several ethical questions such as how to protect animal welfare, and how this may affect organ donation from humans that have been declared brain dead. "The science is so new that we all need to work together to think proactively about its ethical implications so that we can responsibly shape how this science moves forward," says Khara Ramos of the National Institute of Neurological Disorders and Stroke.
The team consulted with neuroethics working group convened by the National Institute of Health’s BRAIN Initiative, which is how they learned of the work, results need to be replicated in other labs to see if they hold up, should they hold up this will challenge many assumptions that underlie legal and ethical controls on experimentation.
According to Nita Farahany, “If it's a dead animal, it's not subject to any research protections because you wouldn't expect that it would suffer from any pain or distress or need to be thought about in terms of humane care. But if that animal's brain can be even partially revived, what do we need to do immediately, today, in order to ensure that there's adequate protections in place for animal research subjects? Immediately people are going to recognize the potential of this research. If, in fact, it is possible to restore cellular activity to brain tissue that we thought was irreversibly lost in the past, of course people are going to want to apply this eventually in humans."
There are protections in place for human research subjects, but that’s not so much the case for dead human tissues, says Christine Grady of the NIH Clinical Center who goes on to add,” Once a human dies and their tissue is in a laboratory, there are many fewer restrictions on what can be done. It is interesting to think about this issue in light of this experiment."
According to bioethicists Stuart Younger and Insoo Hyun such research may complicate efforts to secure organs for transplant from patients that have been declared brain dead; if these patients could become candidates for attempts at brain resuscitation it may become harder for physicians and/or family members to be convinced that additional medical intervention is not warranted or is futile.
What is clear is that if the world suddenly becomes bombarded with a zombie pig apocalypse we now know who to look towards to lay blame.
"There's a big difference between mostly dead and all dead. Mostly dead is slightly alive." ~ The Princess Bride 1987
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