Scientists have managed to restore cell function in the brains of pigs hours after they died, in a breakthrough on Wednesday that experts said threw into question the very notion of what makes animals — or even humans — alive.
▲ A preserved pig brain
TheExperimental Process
The team from the National Institutes of Health BRAIN Initiative, a federally funded US research program, used the brains of 32 pigs that had been slaughtered for food and discarded, without blood or glucose flow, for four hours each.
Then, using a tissue support system that pumps a liquid designed to mimic blood through organs, they rehydrated the brains for a further six hours.
Some brains received the patented life-support solution and others were given a control substance.
The results were astonishing: the brains that received the artificial blood had basic cell function restored. Their blood vessel structure was revived, and the team even observed some localized processes — including in synapses and immune responses — flickering back to life.
▲Neurons(green),astrocytes(red),andcellnuclei(blue)inthebrainsofpigs.Onleft,braintissueleftuntreatedfor10hoursafterdeath;right,braintissuesubjectedtotheexperiment.
Those that received the control solution turned within hours to what researchers described as 'something a bit like yogurt'.
Ethics of animal research
Sestan and his colleagues, led by Zvonimir Vrselja and Stefano Daniele, resolved to test a complex mammal brain's ability to recover, so they devised what they call the BrainEx system.
'Cutting-edge science needs cutting-edge ethics,' says Ramos, who serves as the Neuroethics Working Group's executive secretary.
'There is an existing, robust framework of laws and policies that our funded researchers are expected to follow, but the development and application of new neuro-technologies may require us to examine those ethical standards, and for those standards to evolve.'
For one, the technique opens up questions about the ethical use of non-human animals in experiments. As it stands, two sets of rules apply, one for live animals and another for dead animal tissues, since live animals can experience pain or distress. But which rules apply to BrainEx-treated brains from dead animals, especially if there is a chance they could be partially reawakened?
'There's this kind of gaping hole in our protections of animal research subjects, sincewe now have this part-revived, slightly-alive category with the potential — and, as of yet, not fully understood potential — for recovery of function,' says Farahany, who is also a member of the Neuroethics Working Group.
'If you're seeking to revive pig brains, or other animal brains, does that mean that that becomes an animal research subject, rather than dead tissue?'
Further research into human disease
Experts add that the ethical tradeoff here hinges on BrainEx's ability to further research into human disease — or even save people from brain death.
'We cannot willy-nilly impose, just for our curiosity, pain or agony on another creature unless there's a very good motive and the appropriate experiments,'Koch says. 'Can this be used to rescue brains? Not just gee-whiz, let's see what happens here.'
Experts also say that BrainEx's ethical implications extend to the next logical question: Would it work on humans? On a technical level, Koch says that would not be a major leap, since both pigs and humans have large, complexly folded brains. But Koch and every other outside expert urged caution in moving toward human trials.
On even broader horizons, future versions of BrainEx could complicate the process of organ donation by blurring the lines of brain death, note Case Western Reserve University bioethicists Stuart Youngner and Insoo Hyun in an accompanying commentary published in Nature.
But Kevin Cmunt, CEO of Gift of Hope, one of the United States's largest organ donation networks, doesn't see BrainEx as a major disruption. He says that in many cases, organ donors who are declared brain-dead have suffered oxygen loss well beyond the study's time window, or substantial physical trauma. (Other researchers are creating human-pig chimeras to advance organ transplant options.)
'I think that in the vast majority of brain-dead donors, this intervention would not be material,' he says. 'There may be a small subset of cases where BrainEx could impact the opportunity for donation, but I think it's relatively small.'
And if BrainEx does appear in clinics, Cmunt adds that it would be incorporated into the list of interventions before declaring someone brain-dead or deciding to end life support. The promise of brain recovery could even improve organ donations by giving medical professionals an even greater imperative to maintain circulation.
Then, if the patient is declared brain-dead even after treatment with BrainEx, their organs could be more viable for donation than they would be otherwise.
'I don't necessarily see this as a conflict,' Cmunt says. 'These treatments would certainly be a part of care, just like hypothermia protocols are a part of care, and other things that we try to do to stop damage to organs and brains.'
What Chinese experts say
It is really misleading when certain domestic media outlets use 'back to life' in their headlines because that's still far from being reality, said Tang Cheng, a doctoral candidate and research fellow at the Institute for Neuroscience, Chinese Academy of Sciences.
'The pig brains were still heading for death, which process is held a little slower because part of the cells' functions are partially resumed,' he said, 'But the whole tendency remains the same, without any hint of being reversed.'
'In the future that, the standards on defining a person brain-dead may have to be raised,' said Wang Yue, a professor at School of Health Humanities, Peking University.
'That may not be good news for those needing an organ transplant as the gap time of picking organs from the brain-dead person's body and transplanting it to a patient's body might be shortened, which in turn may result in organs being 'wasted'.'
But there is no need to overly worry about it, he added. 'There will be other technologies, such as 3D printing, cloning, as well as gene-based manufacturing that will produce the organs needed for transplantation in the future.'
Source: China Daily,National Geographic
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