Immortality and Life Extension: Can Science Cure Death? (1)
Achille De Tommaso
Physicist | Expert in Technologies, Artificial Intelligence, Genetics, Biology & Anthropology | Researcher on the Impact of Technology on Living Systems | Author | Advocate for Innovation, politics and Knowledge Sharing
by Achille De Tommaso
According to biology, death might be a reversible phenomenon; and if nothing lasts forever, perhaps death doesn’t either. Can we reverse it? The way we determine death is often based on a legal construct: but is it therefore a biological fact or a social determination?
In 1968, a committee of experts convened at Harvard Medical School to discuss the definition of “death.” For centuries, the criteria for determining death had been based on how people appeared to be dead: “when breathing ceased and a person had no pulse, they were no longer alive.” However, the group at this conference proposed adding a second criterion: the absence of brain activity. This made sense; the brain controls other organs and regulates breathing: if there is no breathing, there is no brain activity; and since there is apparently no way to repair a non-functioning brain, a person in such a state is defined as dead.
The timing of this decision was not coincidental. Just a year before, in 1967, doctors had performed the first heart transplant; so, the fact that a heart was no longer beating was not sufficient to declare its owner dead. Beyond alleviating the burden of prolonged and meaningless treatment, the new approach, based on brain death to define the death of an individual, also served to avert controversies over when doctors could eventually retrieve organs: if an organ donor’s brain is dead, their organs can be recovered.
Over time, brain death became the most widely accepted definition of biological death, and this view was codified by medical professionals, as exemplified in a 2019 position statement by the American Academy of Neurology.
Is everything clear?
No!
There have been, in reality, some rare cases, such as that of a certain Jahi McMath, where medical interventions successfully kept the person “alive” for years after their brain had ceased functioning. If this is true, and some endocrine functions can persist without brain activity, there is room for critics to argue that the current standards for defining “death” are incomplete.
Today, there is also some doubt as to whether brain death is irreversible.
One of the first things learned in medical school is that brain cells die after several minutes without oxygen.
Yet, a Yale neurobiologist, Nenad Sestan, who studies genes that control how neurons grow and form connections in the developing brain, discovered that this is not always the case. On several occasions, he found that someone had left a brain tissue sample out for too long before transferring it into a fluid for experiments; and Sestan was still able to recover living cells from the brain tissue. His cell revival system initially worked when a brain had “arrived late” due to a flight delay and then worked again on a second brain that his researchers cut and recovered to ensure that the previous results were not just a stroke of luck. Sestan began to wonder: if living cells can be preserved from a dead brain, why not try to revive the entire organ?
Using pumps, heaters, and assorted filters to circulate a blood substitute, Sestan and his colleagues put together a perfusion system they called BrainEx. This system was patented, and the scientists who worked on it achieved astounding results. In a 2019 article (1), the team described how BrainEx revitalized key features of pig brains retrieved from a slaughterhouse. Four hours after the pigs’ death, neurons were reactivated, blood vessels functioned, and the brain’s immune cells worked.
After the BrainEx paper was released, scientists and doctors flooded Sestan with ideas about “what to do next”; like, “Well, you should absolutely try doing this on the whole body.” And so it was: the BrainEx methodology was expanded to a whole-body version, named OrganEx.
领英推荐
Within it, OrganEx functions like Extracorporeal Membrane Oxygenation, or ECMO (the tried-and-tested system used, for example, in open-heart surgery). The system has a pump that mimics heart function and an oxygenator that mimics lung function. But in addition, OrganEx also includes a blood filtration unit, along with additional pumps, tubes, and sensors, to perform real-time measurements of metabolites, gases, electrolytes, and pressures. However, note that there are also original mixtures that the system introduces into the body: a priming solution to correct electrolyte and pH imbalances, bovine-derived hemoglobin to carry oxygen, and about a dozen drugs: anti-inflammatories, antioxidants, antihistamines, antibiotics, and various neuroprotective agents. And hormones. The originality of the system lies in this mixture, forming the basis of the patent.
Fundamentally, OrganEx adds a sort of cellular life support, based on the aforementioned drugs, to traditional ECMO. Moreover, it revives the body more slowly. When cells have been deprived of oxygen for a while, suddenly connecting them to fresh blood can start a cycle of stress and damage that kills them, a problem called ischemia-reperfusion injury. What OrganEx does instead is a kind of slow resuscitation: a gentler process of reviving cells that have already begun to die.
The experiment was conducted on pigs. It took about five hours to prepare the solutions and machines and another seven hours to conduct monitoring and measurements on 10 pigs. The scientists worked on one animal at a time, each sedated and kept fully anesthetized; they inserted a tiny electrode through a hole in each animal’s chest and touched its heart to induce cardiac arrest. Two monitors, one for the heart and one for brain activity, eventually showed flat lines. The pigs were “dead.”
After an hour, the real test began: the scientists connected five animals to the OrganEx system and the other five to a standard ECMO to check for differences in results. The experiment was supposed to last for the next six hours, but the first and most obvious changes occurred after about half an hour: heart monitors attached to four out of five pigs treated with OrganEx began to light up. Electrical activity in the heart had resumed spontaneously, without the need for chest compressions or other obvious life-saving measures. None of the five animals in the group treated with traditional ECMO showed any electrical activity or contractions: they were truly dead.
After six hours of perfusion, the researchers administered euthanasia drugs to the pigs and disconnected the machines. They then proceeded to perform careful autopsies, examining the tissue of the animals' vital organs, including the heart, lungs, liver, kidneys, and brain, under a microscope. The shape and organization of the cells appeared significantly better in samples treated with OrganEx compared to those from pigs subjected to ECMO. Other tests showed the restoration of specific cell repair gene activity after treatment with OrganEx. OrganEx was so effective that some changes were even visible to the naked eye. The treated pigs did not exhibit typical signs of death, such as muscle stiffness (rigor mortis) and purplish discoloration (livor mortis).
And now to the brain.
In preparation for brain imaging, the researchers had inserted a catheter into the pig’s neck and sprayed contrast dye into the carotid artery: a procedure that makes it easier to see blood vessels on an X-ray. Well, when the dye was shot through the tube, something surprising happened: the animal seemed to turn its head. “It was just a few moments. It wasn’t as if the animal was trying to get up, but it wasn’t just a twitch either.” Andrijevic, one of the experimenters, described it as a “complex” movement and suggested that OrganEx perfusion might restore neuromuscular junctions, where nerves and muscle fibers meet.
“What does this mean?” The scientists, cautiously, respond, “We’re not sure”; and, in practice, they are still pondering what the results of OrganEx mean. The experiments were conducted on animals, and it will take years before they can influence human medicine. However, at the cellular level, they might show that death may not proceed as quickly or definitively as once thought.
For people who collapse due to a heart attack and remain on the ground, unattended, for 10 minutes, the results raise a key question: when can we lose hope? When are they really dead? And it begs the question, for example, of whether death could be “reversible” in situations like heart attacks. One could imagine using OrganEx instead of ECMO to intervene after cardiac arrest; without the reperfusion injury that ECMO can cause, survival rates might improve.
The problem is that the idea of reversibility strikes at the heart of the debate over the medical definition of death. As Sestan says, “The way we determine death is based on a legal construct, a social determination, or a biological fact?”
For now, it often relies on a lack of brain function, but you don’t have to go far in medical history to know that nothing lasts forever. Perhaps not even death.
REFERENCES