'I have an obligation to swing for the fences'

Philanthropic funds at just the right time helped Mark Roth plumb the secrets of immortality
Dr. Mark Roth and other Hutch scientists explain why fearless science matters. StraightEIGHT Films

Tiptoeing toward immortality will only get you so far. Eventually, you need to leap.

Seventeen years ago, Dr. Mark Roth, a basic scientist at Fred Hutchinson Cancer Research Center, knew he’d tiptoed as far as possible in his search for the biological key to immortality. He had discovered what he could about suspended animation, a dormant state that can extend life under harsh conditions, by studying oxygen deprivation in flies and worms.

Now, he needed to leap: Instead of removing oxygen, Roth wanted to try removing the need for oxygen itself by using a toxic gas. Roth needed the gas, but above all, he needed funds. Standard government granting agencies like the National Institutes of Health wouldn’t bet on such a far-fetched scientific aim.

“I had no grant support, I was on interim funding,” Roth recalled. “There was healthy skepticism that this wouldn’t be anything more than dangerous.”

Roth turned to Dr. Lee Hartwell, who in 2003 was the Hutch’s president and director and had received the 2001 Nobel Prize in physiology or medicine for his work on nucleated cells’ cycle of growth and division.

Hartwell didn’t hesitate.

“His discovery was so unique and had such tremendous long-term potential that there was no question in my mind that we should support it,” said Hartwell.

He drew on generous philanthropic donations to give Roth the boost he needed.

With $20,000 provided by Hartwell and Dr. Mark Groudine, who directed the Hutch’s Basic Sciences Division at the time, Roth showed that the toxic gas, hydrogen sulfide, could be used to induce reversible suspended animation in mice. He then parlayed this success to secure further funding from the Defense Advanced Research Projects Agency, and in 2007 received a MacArthur Genius Award that continued to support his studies of suspended animation.

Now, Roth’s work is paying off. He found that iodide, a much safer compound with similar properties to hydrogen sulfide, may be nature’s secret to help animals successfully reanimate after naturally dropping their metabolic rate in hibernation.

Iodide’s unique ability to act as a continually renewable antioxidant allows it to protect damaged tissue, a phenomenon that Roth is capitalizing on to improve human health. With Faraday Pharmaceuticals, the biotech company Roth spun out of the Hutch, he conducted clinical trials that showed that iodide can protect patients from trauma damage by safely reanimating dying tissue.

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“Philanthropic dollars, because they're handled so well, and judiciously given out by the senior leadership, can be used to take long shots,” Roth said.

The sea monkeys’ secret

While Roth started his scientific career asking more conventional questions about genes and chromosomes, he harbored an interest in something bigger.

“What I was really interested in was immortality,” he said. “What are you doing when you’re doing nothing?”

When you look for immortality, you find stasis, Roth said. Examples include seeds and fungal spores. Humans’ egg cells are held in a years-long suspended state until called upon to complete the last stage of development and become a fertilizable egg that’s released from the ovary.

When he bought bags of sea monkeys for his children, Roth was only somewhat interested in the moment of their reanimation.

“I wanted to know what was going on in the bag while they were sitting in the shop for, I don't know, years?” he said.

Roth was also inspired by stories of people who ought to have died but didn’t: A fisherman who appeared to die from extreme cold only to wake up hours later, or a boy who crossed the Pacific Ocean in the wheel well of a jet and lived to tell about it. He became a collector of near-death-experience stories, and finally decided to chuck genetics and study the phenomenon.

Though Roth started out studying oxygen deprivation, his experiments soon showed him that it likely wasn’t the oxygen deprivation itself that helped people survive extreme environments, but a reduction in their need for oxygen. A decrease in the basal metabolic rate, akin to that seen in hibernating animals.

But how could such a state be induced?

Caves bring an epiphany

A NOVA documentary on New Mexico’s Lechuguilla cave gave Roth the epiphany he needed.

At one point, Roth recalled, experienced spelunkers warned the filmmakers against going too deep into the caves without a respirator, due to the deadly levels of hydrogen sulfide gas. Roth awoke that night with a realization: toxic gases like hydrogen sulfide could be the key to reducing the body’s oxygen consumption and basal metabolic rate.

Hartwell provided Roth with the seed funding, which came from philanthropic donations to the Hutch, to test his then-outlandish theory. 

In a recent In-Focus Friday video, Hutch President Dr. Tom Lynch speaks with the Hutch's head of philanthropy, Kelly O'Brien, about how philanthropic donations drive scientific advances. Video by Robert Hood / Fred Hutch News Service

“Up until the work that I did, it was believed that you can't get below basal metabolic rate [of oxygen consumption],” Roth said. “That's simply false.”

Instead, he found that by using agents previously thought of as toxins, such as hydrogen sulfide, he could depress an organism’s basal metabolic rate, thereby depressing its demand for oxygen.

“What I'm actually trying to do in the lab is extend survival limits,” Roth explained. "I'm trying to make it so that cells, tissues, or humans do not die when they are subject to certain vicissitudes of life,” he said.

For example: When tissues are undergoing trauma, such as heart tissue during a heart attack.

When oxygen can’t reach an area of heart tissue, that area “enters into suspended animation. It's having a near-death experience,” Roth said. “The rest of your body remains animated, the heart continues to beat, except this chunk. … You enter into suspended animation quite easily when the blockage occurs, but you don't reanimate right.”

It’s that poor reanimation, caused by the rush of oxygen radicals that flood the previously blocked heart tissue as blood flows again, that causes lasting damage. Iodide — quite safe compared to hydrogen sulfide — buffers the body against this damage.

“It basically means the heart attack isn't doing as much damage to you,” Roth said.

In addition to testing iodine against heart attack and trauma, he is working with the U.S. Army to test whether iodine may help improve outcomes in soldiers injured on the battlefield.

“I'm not very fearful of failure as a whole,” Roth said. “I've been embarrassingly lucky to work at a place like the Hutch, to be supported as I have been … I have an obligation to swing for the fences.”

Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

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