Fact Check: Scientists revive pig-brains and other organs after death.
Dr Frankenstein would be pleased.
This will be next.
When is it All Hallow’s Eve?
This is kind of a Halloween fact check: but it is completely true, it’s not fiction or some sort of ghost story. Now, right now in Western Australia where I live, it is not Halloween any longer but about 10:03 am on All Saint’s Day, however, in Yale University from whence this information originates it is currently 10:03 pm on October 31st 2022, so it’s still Halloween there…
Dead Pig Organs Revived by scientists from Yale.
A team of scientists from Yale University have revived dead pig organs, that had been dead for one hour. They connected pigs to a system called OrganEx that pumped a blood substitute containing the animals’ blood together with anticoagulants and other compounds throughout the animals’ bodies.
It slowed decomposition quickly restored some organ function in the heart, liver and kidneys. OrganEx apparently helped to preserve the integrity of some of the brain tissue as well, but the researchers did not observe any activity that would indicate the animals had regained consciousness or sentience – this was probably because they intentionally gave the animals sedatives just in case they regained consciousness!
The lead researchers were David Andrijevic, Zvonimir Vrselja, Taras Lysyy and Shupei Zhang, together with a large team of scientists from the Department of Neuroscience at the Yale School of Medicine. Doctor Frankenstein does not seem to have been present (joke.)
Their research continues Zvonimir Vrselja’s research with Stefano G. Daniele et al at the Neuroscience departments of Yale three years ago, reviving pig brains for four hours after death.
Ethical Concerns? Noooo, surely not….
This research has raised ethical concerns. Nita A. Farahany, Henry T. Greely and Charles M. Giattino wrote an article in Nature magazine expressing the need for new guidelines.
In our view, new guidelines are needed for studies involving the preservation or restoration of whole brains, because animals used for such research could end up in a grey area — not alive, but not completely dead.
There are five areas they believe should be addressed.
First, how should researchers try to detect signs of consciousness or sentience?
EEG activity, which is actually detectable in those under amnesia, is not sufficient. They suggest using transcranial magnetic stimulation (TMS) - holding a magnetic coil near the head - and/ or magnetic resonance imaging, which can show particular patterns of neuronal activity that can indicate consciousness.
Second, which species make appropriate models for this type of research on brain perfusion? And what kinds of research and results would be needed to justify the use of other models?
They specifically say researchers should proceed cautiously with testing in higher mammals, pigs, dogs and primates.
Third, until more is known, is the use of neuronal activity blockers sufficient to safeguard against the emergence of capabilities associated with sentience, such as the capacity to feel pain? It might be necessary to apply BrainEx or similar systems to mice or rats, both with and without neuronal activity blockers, to better understand the blockers’ role.
Fourth, under which scenarios should anaesthetics be used in follow-on studies, to safeguard against the possibility of inducing any experience similar to pain or distress? And under what scenarios might it be permissible not to use them? (We think that the use of anaesthetics in follow-on studies should be mandatory at this time, given all of the unknowns.)
Finally, for how long should BrainEx or similar artificial circulatory systems be run? Such systems might be effective for only a certain period of time, or there could be a limit as to how much recovery can be achieved. This knowledge will inform analyses of risks and benefits.
The Abstracts
2022 study - reviving pig organs
After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.
2019 study - reviving pig brains
The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.
https://www.nature.com/articles/d41586-022-02112-0
tps://www.nature.com/articles/s41586-022-05016-1
Vrselja, Z., Daniele, S.G., Silbereis, J. et al. Restoration of brain circulation and cellular functions hours post-mortem. Nature 568, 336–343 (2019). https://doi.org/10.1038/s41586-019-1099-1
Andrijevic, D., Vrselja, Z., Lysyy, T. et al. Cellular recovery after prolonged warm ischaemia of the whole body. Nature 608, 405–412 (2022). https://doi.org/10.1038/s41586-022-05016-1