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28 June 2016
BEC CREW 23 JUN 2016
When a person's heart and brain have stopped ticking, and their respiratory and circulatory systems grind to a halt, it’s time to declare death. The body has shut down, there is no more life. Or is there?
A pair of papers published this week discuss evidence that certain parts of the body are still firing even days the rest have stopped functioning, and it could change the way we think about organ transplants and time of death.
Led by microbiologist Peter Noble, a team from the University of Washington has been investigating the gene activity in deceased mice and zebrafish, prompted by previous research that identified a handful of genes in human cadavers that were active more than 12 hours after death.
The researchers ended up identifying more than 1,000 genes that were still functioning even days after death, but it wasn't like they were taking a bit longer to sputter out than the rest of the body - they actually increased their activity.
In mice, 515 genes were seen kicking into gear, and were functioning at full capacity up to 24 hours after death. In the zebrafish, 548 genes retained their function for four whole days after the animals had died before showing any signs of winding down.
The team figured this out by measuring the fluctuating levels of messenger RNA (mRNA) present in the mice and zebrafish as they died, and up to 96 hours afterwards. MRNA is kind of like a blueprint - it tells our genes which proteins need to be produced by which cells, so if there's more mRNA in a cell, that means more genes are currently active.
What’s maybe even stranger than that is the fact that these 'postmortem' genes weren’t just any genes, they were the kind of genes that ramp up during emergencies.
As Mitch Leslie reports for Science Magazine, we’re talking about tasks like stimulating inflammation, firing up the immune system, and counteracting stress. Some of the genes they identified usually switch on to help form an embryo, and then are never heard of again... except after death, apparently.
"What’s jaw-dropping is that developmental genes are turned on after death," Noble told Leslie.
It’s not all beneficial genes, though, the team also found that certain genes that promote cancer growth also sparked after death in these animals, prompting the researchers to suggest that in a newly deceased corpse, the body reverts to the cellular conditions of a rapidly developing embryo.
Maybe building a new body and trying desperately to reanimate a dead body are pretty much the same thing to the hundreds of 'zombie' genes.
Though these hard-working genes will never be strong enough to actually get the job done and bring a dead mouse, zebrafish, or human back to life, understanding what they’re doing and why could have a massive impact on patients living with transplants.
Studies have found that organ transplant recipients have much higher risk of developing 32 different types of cancer, including non-Hodgkin lymphoma, and kidney cancer, and liver cancer, and doctors have been struggling to mitigate this.
"While transplantation is a life-saving therapy for patients with end-stage organ disease, it also puts recipients at an increased risk for developing cancer, in part because of medications administered to suppress the immune system and prevent rejection of the organ," says Eric A. Engels of the US National Institutes of Health's (NIH) National Cancer Institute.
"The cancer risk among transplant recipients resembles that of people with HIV infection, whose risk is elevated for infection-related cancers due to immunosuppression."
The crazy amounts of immune-suppressing drugs transplant recipients have to take to make sure their body doesn’t reject the organ could partly explain the heightened risk of cancer, but active postmortem genes in the organ could also be at play, Noble told Science Magazine.
The papers have been published on pre-print website bioRxiv here and here, and we need to stress that they have not yet been peer-reviewed.
By publishing them online, Noble and his team are inviting researchers to get in early and critique their work before it’s submitted to a journal, which is awesome, but it means until these results are independently verified, we need to remain skeptical. This is especially pertinent, seeing as similar findings still need to be achieved in humans - not just lab animals.
But none of us would argue that we've got death even remotely figured out, so this could be the beginning of a whole new way of defining what it means for us to be alive, dead, and not-quite-done. "[We can probably get a lot of information about life by studying death," says Noble.
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