expert reaction to paper suggesting that cellular and tissue function can be restored in pigs after death – Science Media Centre

August 3, 2022

A paper published in Nature suggests cellular recovery can occur in pigs after death.

Prof Martin Monti, Professor of Cognitive Psychology, University of California Los Angeles (UCLA), said:

Biological death is more like a cascade of dominoes, with one event triggering the next, than an instantaneous transition. What is ground-breaking about this technology is that this cascade can be halted in some organs if only the right cellular environment and metabolic parameters can be restored. The potential implications, if this will ever be successfully translated to humans, are huge: how many more lives could be saved through transplantation each year thanks to greater organ viability?

What this technology did not do, however, was restore any form of brain network activity and any associated function. Whether this is due to brain tissues having a faster death cascade than other organs or other factors remains unclear.

What is clear, however, is that this technology is not about magically reviving dead tissue. It is about expanding the window for restoring organ function by interrupting the death cascade.

Dr Anders Sandberg, Senior Research Fellow at the Future of Humanity Institute, University of Oxford, said:

When blood circulation stops, cells begin to die due to lack of oxygen, and chemical changes begin that harm tissues and organ function. At normal temperature, irreversible changes set in after a few minutes. What this paper shows is that significant improvements are possible in how long after death preservation methods to keep organs alive can be started (up to an hour), and that some of the cellular damage can be partially reversed.

While the experiment was done on pigs, helping humans is an obvious goal, and the most obvious impact is on organ donation. Currently, most organ donation happens after brain death: the brainstem has permanently ceased functioning, but the body is otherwise functional. These cases are rarer than circulatory death where the heart has irreversibly ceased functioning. However, in these cases, there will be a period of no circulation before artificial circulation can be instituted and organs are likely to be damaged. The system in the paper may help overcome this problem, making more transplants possible.

Ethically, this seems to beunproblematic good news. However, further in the future this kind of method may also make treatment directly after a stroke or major trauma more effective: by saving patients that would otherwise have died, it might reduce the number of available transplants. This may still be good news, but there is a risk that it mainly preventspeople from dying rather than making them recover. There is a challenging ethical issue in determiningwhen radical life support is just futile, and as technology advances we may find more ways of keeping bodies alive despite being unable to revive the person we actually careabout. Much work remainsto find criteria for when further treatment is futile, and alsoin how to get people back from the brink.

Right now, the ethically important aspect of this paper is that it shows that the changes happening after stopped circulation can be slowed or reversed with the right treatment: there is more hope for patients in this state. Death is not an instantaneous event but rather agradual process, and we have gained a further tool to nudge it. Once, lack of breathing was regarded as a sign of permanent death, until artificial breathing merely made it a dangerous state to be in. Later, other technologies have pushed back the point of no return, first to cardiac arrest, and later to brain death. OrganExshows that there is more medical wiggle room in cases with no circulation to fix things than previously looked possible: related methods may make new forms of surgery possible. Paradoxically, this makes the futility debate harder since there is a bit more hope. However, it is better to have more options to save lives than fewer, even if hard moral choices have tobe made.

Doubtless some readers will bring up cryonics, the practice of cooling down bodies to extremely low temperatures after death hasbeen declared in the hope that future medicine will be able to revive them and repair the damage from both the terminal cause and the suspension process. This is not what OrganExis about, but the technology will doubtless be of great interest to cryonics organisations as a way of reducing the damage while temperature is lowered. One of the largest practical hurdles is the often excessivetime between circulation stopping and damage-reducing suspension procedures starting: this technique may buy valuable time. The big question about whether future revival is going to be possible remains, but at least one can improve the present practice to boost the chances.

Dr Sam Parnia MD PhD, Associate Professor of Critical Care Medicine and Director of Critical Care and Resuscitation Research, New York University Grossman School of Medicine, said:

The press release is accurate but if anything underestimates the significance of these discoveries.

This is a truly remarkable and incredibly significant study. It demonstrates that after death, cells in mammalian organs (including humans) such as the brain do not die for many hours. This is well into the post-mortem period.

Consequently, by developing this system of organ preservation (using organ Ex in humans, which is entirely feasible), in the near future doctors will be able to provide novel treatments to preserve the organs post-mortem. This will enable access to many more organs for transplantation, which will lead to 1000s of lives saved every year.

Perhaps, as important is the fact that the OrganEx method can be used to preserve organs in people who have died, but in whom the underlying cause of death remains treatable. Today, this would include athletes who die suddenly from a heart defect, people who die from drowning, heart attacks or massive bleeding after trauma (such as car accidents). The OrganEx system can preserve such peoples organs and prevent brain damage for hours in people after death. This will provide time for doctors to fix the underlying condition (such as a blocked blood vessel in the heart that had led to a massive heart attack and death, or repair a torn blood vessel that had led to death from massive bleeding after trauma), restore organ function and bring such people back to life many hours after death. As such otherwise healthy people, including athletes who die, but in whom the cause of death is treatable at any given time can potentially be brought back to life, and if the cause of death is not treatable, then their organs can be preserved to give life to thousands of people every year.

Finally, this study demonstrates that our social convention regarding death, ie. as an absolute black and white end is not scientifically valid. By contrast, scientifically, death is a biological process that remains treatable and reversible for hours after it has occurred.

For decades millions of people have reported lucid consciousness and a detailed reevaluation of all their own actions, thoughts and intentions throughout life, when on the brink of death, or after crossing the threshold of death. These recalled experiences surrounding death or so called near death experiences were often been dismissed. However, this study and others suggest consciousness may not be annihilated at the time of death. This further reinforces the need to study consciousness and recalled experiences surrounding death in an unbiased scientific manner. Scientists can study what happens to the human mind and consciousness after death and provide answers to the age old question of what happens to us all after we die through the prism of science.

Cellular recovery after prolonged warm ischaemia of the whole body by David Andrijevic et al. was published in Nature at 16:00 UK time on Wednesday 3rd August 2022.

DOI: 10.1038/s41586-022-05016-1

Declared interests

Prof Martin Monti: No conflict of interest.

Dr Sam Parnia: I donthave any conflicts. However, I do conduct other research into methods to preserve the brain after cardiac arrest.

For all other experts, no reply to our request for DOIswas received.

Read more:

expert reaction to paper suggesting that cellular and tissue function can be restored in pigs after death - Science Media Centre