Zombie Genes Awaken After Death in the Human Brain

Some neuronal genes experience a surge of activity after the brain has stopped functioning, continuing to grow cells as if they believe in a possible resurrection. This raises questions about the very definition of death.

Brain

An update to the definition of death may be needed

The World Health Organization (WHO) defines death as “the irreversible disappearance of brain activity.” It’s a definition that probably needs to be revised in light of a new study published in the journal Scientific Reports. The study showed that some genes remain remarkably active in the human brain for up to 24 hours after death.

When the heart stops beating, blood flow to the brain stops, causing neurons to die. After a few minutes, the brain shows no electrical activity. However, animal studies have shown that some genes remain active after death. In mice and zebrafish, more than a thousand genes continue to transcribe molecules for up to four days after death. But until now, this phenomenon has not been observed in humans.

For their new study, Jeffrey Loeb and his colleagues at the University of Illinois in Chicago had exceptional access to freshly removed human brain tissue from epileptic patients who had recently undergone surgery to help control their seizures. They then simulated a controlled death and examined gene expression during the first 24 hours after death.

‘Zombie’ genes that wake up when others go to sleep

The activity of most of the genes studied remained relatively stable over 24 hours. These are all genes that perform basic cellular functions. Another group of genes known to be present in neurons and shown to be intimately involved in human brain activities such as memory, thinking, and seizure activity deteriorated rapidly in the hours after death. Finally, for the third group of genes, activity increased sharply as that of the others declined, peaking 12 hours after death. These “zombie genes,” as Jeffrey Loeb calls them, are specific to inflammatory cells called glial cells. As the zombie genes wake up and continue to transcribe proteins and regulate vital functions, they grow and form long, arm-like appendages for up to several hours after death, the authors describe.

What mechanism might drive genes to form cells when the body is permanently dead? “It’s not surprising that glial cells continue to grow after death, because they play an inflammatory role and their function is to repair damage after brain injury, such as oxygen deprivation or stroke,” explains Jeffrey Loeb. Thus, the body would be “fooled” into thinking it could reverse the course of events by waking up the inflammatory cells.

In the study of mice and zebrafish, other zombie genes that are normally attributed to embryonic development and remain silent after birth suddenly awoke after death, as did other genes involved in cancer development. Another study published in 2018 had shown that some neurons become more active during sleep, causing many “mini-tunings” during the night.

Could we then imagine the recovery of brain function after death? In 2019, researchers had succeeded in reviving decapitated pig brains and restoring certain neuronal functions. Not enough to create a global level of consciousness, but a partial challenge to the definition of death.