A study just published in the April 17th issue of Nature (Vol. 568, pages 336-343, Restoration of Brain Circulation and Cellular Functions Hours Post-mortem) raises a number of interesting ethical and scientific questions. In a short summary, the study used a system called BrainEx that perfused brains removed from pigs that had been killed up to four hours earlier. The solution used contained a host of nutrients and chemicals that promotes recovery from lack of oxygen. This enabled them to restore some functional activity as well as allow preservation of structural activity four hours after “death”. In other words, a dead pig’s brain began to show biochemical and electrical signs of functioning at a cellular level, but no EEG signs associated with what we consider to be “consciousness”.
Traditionally, we have considered 4-6 minutes without oxygen as being the upper limit of time before irreversible brain injury and death occurs. In this study, pigs’ brains (removed from their skulls) were “revived” after four hours. The authors conclude that “under appropriate conditions the isolated, intact large mammalian brain possess an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval”.
What are some of the questions raised? First of all, are we being too quick to assume that a brain has been irreversibly damaged after circulation has stopped? Although the pigs’ brains did not show any EEG activity, could this have recurred if they had continued with the perfusion for a much longer time than they did in their study? Although they used pig brains, we need to realize that pigs are more closely related to us, both immunologically and structurally, than we give credit for. Bear in mind, that pig valves were commonly used in human hearts, and other tissues are being considered in xenotransplantation (I suggest you read about this subject, further, since some of the work being done is fascinating). Are these findings going to be applicable to the human brain?
The implications for when to consider someone “dead” and an organ donor have already arisen as a result of these preliminary findings. This was touched upon in a “Comment” to the study, entitled “Pig experiment challenges assumptions around brain damage in people”, in the same issue.
Clearly, this study needs to be replicated and the evolution from research to clinical application is a very long way off. The input of a number of specialists ranging from medical ethicists to veterinarians for choosing which animals should be used for future studies, and what safeguards should be in place will be needed. This and other apprehensions were raised in another “Comment”, entitled “Part-revived pig brains raise slew of ethical quandaries” found in the same issue of Nature.
In the study, there was no measurable EEG, and hence the conclusion that no consciousness or pain was being produced in the animals. It is important, however, to note that the EEG is the summation of the synchronized firing of multiple neurons within certain areas of the brain, and not a few or smaller groups firing. Does the perception of pain or minute levels of consciousness require EEG findings or does the firing of certain neurons and isolated activity at certain synapses in specific sub- areas accomplish the same?
There is still so much that we don’t understand about the brain and the phenomenon of “perception” versus “awareness” and what constitutes consciousness. We are a long way from uttering the oft-quoted Dr. Frankenstein comment, “It’s alive!”, but this study starts to question some of our long-held beliefs about what constitutes death and when does irreversibility of biological function take place? Stay tuned for further studies in this area, but draw no conclusions yet!