Hundreds of genes seen sparking to life two days after death

The discovery that many genes are still working up to 48 hours after death has implications for organ transplants, forensics and our very definition of death

When a doctor declares a person dead, some of their body may still be alive and kicking – at least for a day or two. New evidence in animals suggests that many genes go on working for up to 48 hours after the lights have gone out.

This hustle and bustle has been seen in mice and zebrafish, but there are hints that genes are also active for some time in deceased humans. This discovery could have implications for the safety of organ transplants as well as help pathologists pinpoint a time of death more precisely, perhaps to within minutes of the event.

Scientists at the University of Washington, Seattle, and their colleagues investigated the activity of genes in the organs of mice and zebrafish immediately after death. They did this by measuring the amount of messenger RNA present. An increase in this mRNA – which genes use to tell cells to make products such as proteins – indicates that genes are more active.

Noble’s team measured mRNA levels in zebrafish, and in brain and liver samples from mice at regular intervals for up to four days after death. They then compared these with mRNA levels measured at the time of death.

“Hundreds of genes with different functions woke up after death, including fetal development genes”

As you might expect, overall mRNA levels decreased over time. However, mRNA associated with 548 zebrafish genes and 515 mouse genes saw one or more peaks of activity after death. This meant there was sufficient energy and cellular function for some genes to be switched on and stay active long after the animal died.

These genes cycled through peaks and dips in activity in a “non-winding down” manner, unlike the chaotic behaviour of the rest of the decaying DNA, says Noble.

Hundreds of genes with different functions “woke up” immediately after death. These included fetal development genes that usually turn off after birth, as well as genes that have previously been associated with cancer. Their activity peaked about 24 hours after death.

A similar process might occur in humans. Previous studies have shown that various genes, including those involved in contracting heart muscle and wound healing, were active more than 12 hours after death in humans who had died from multiple trauma, heart attack or suffocation (Forensic Science International, doi.org/bj63).

The fact that some genes associated with cancer are activated after death in animals, might be relevant for reducing the incidence of cancer in people who receive organ transplants, says Noble. People who get a new liver, for example, have more cancers after the treatment than you would expect if they hadn’t had a transplant. The regime of drugs they need to take for life to suppress their immune system so it doesn’t attack the new organ may contribute to this, but Noble says it is worth investigating if activated cancer genes in the donor liver could play a part.

So why do so many genes wake up after death? It is possible that many of the genes become active as part of physiological processes that aid healing or resuscitation after severe injury. For example, after death, some cells might have enough energy to kick-start genes involved in the inflammation process to protect against damage – just as they would if the body were alive.

Alternatively, a rapid decay of genes that normally suppress other genes – such as those involved in embryological development – might allow the usually quiet genes to become active for a short period of time.

For forensic scientists, knowing how gene activity rises and falls at different time points after death is useful for working out when someone died. Measuring mRNA would allow us to nail down the time since death to hours and possibly even minutes, rather than days, helping to reconstruct events surrounding the death.

It is good to see such progress being made in this area, says Graham Williams, consultant forensic geneticist at the University of Huddersfield, UK. “But substantial work is required before this could be applied to case work.”

The research also raises important questions about our definition of death – normally accepted as the cessation of a heartbeat, brain activity and breathing. If genes can be active up to 48 hours after death, is the person technically still alive at that point? “Clearly, studying death will provide new information on the biology of life,” says Noble.