Mark Roth, Spontaneous Combustion and Hibernation

In this month’s Esquire meet Mark Roth—certified genius, a fellow Seattleite and one of the more innovative scientists on the planet.

Back when I was a fresh and new graduate student, I took a course co-chaired by him and fellow Hutch professor Dan Gottschling—on the chromosome—that propelled me forward to my thesis project. At the time, he was working on a truly funky pair of problems: Why don’t we spontaneously combust? How do some animals hibernate?

In a strange way, these unknowns are related.

Inside each of our cells are mitochondria. These are the reactors powering our bodies. At the core of mitochondria is something called the electron transport chain—in which the energy contained in electrons gleaned by breaking down fats and sugars is first used to pump hydrogen, and later these pumped hydrogen are converted into useful energy stores called ATP. High energy electrons go in, tired electrons come out at the end.

The used up electrons need to go somewhere. The mitochondria stuff them onto a passing oxygen molecule, creating carbon dioxide. Basically, it’s just like when a candle burns; in a living system, it’s called respiration. And like any combustion, it generates heat.

If left unchecked, if nothing slowed down the electron transport chain in this process, we’d probably light on fire. Something has to be putting on the breaks. In other words, if an individual was mutant for this slowing down mechanism, they might burst into flames.

Well, what could it be?

Dr. Roth has a guess: Hydrogen Sulfide. While about one in five molecules in air today—once you’ve stripped out the water—are oxygen, back when life started there was almost no free oxygen in the atmosphere. It took green living things and photosynthesis to produce all of this free oxygen gas. Before our present cycle of photosynthesis and respiring—most living things lived off of chemical sources of energy, things like volcanic vents. Chief among the fuel sources? Sulfur containing compounds.

Where we live—where most creatures live—on the planet, there isn’t much sulfide gas. Yet, our cells all make a small amount of it. What if this gas was the mystery regulator of the electron transport chain?

Mark discovered that when you add hydrogen sulfide to mitochondria, the gas reversibly slows down the electron transport chain. His prediction was right!

Next he considered, if you slow down the chain, and thus the need for oxygen, perhaps you could make an entire animal hibernate just by giving it this gas. In came the mice, and what followed was a groundbreaking paper in the Journal Science, H2S Induces a Suspended Animation”“Like State in Mice.

Clinical trials, on humans are ongoing. The implications are staggering—for space travel, for management of traumatic injury, for war and even for immortality.