This Scientist Is Searching For Secrets Of Life – Mark Roth examines those who have come perilously close to death in order to help them live.
People who have been stranded in the frozen wilderness of Mount Rainier or stowed away in the wheel well of a trans-Pacific jet. People who have had massive heart attacks or been in car accidents that have crushed their bodies.
Roth sees a link between these disasters and something seemingly unrelated: immortality. According to him, both conditions “press pause” on life. It’s acting dead without actually being dead. [This Scientist Is Searching For Secrets Of Life]
“A simple link can be drawn between near-death experiences and immortality. “They’re both dormant — they’re in’suspended animation,'” Roth explained. “There is something about a near-death experience that is not so much near death as it is what I call a far-death experience.”
To equate being almost dead with living forever is admittedly strange. However, Roth, a biochemist and cell biologist at Seattle’s Fred Hutchinson Cancer Research Center, as well as an entrepreneur and past MacArthur “Genius Grant” recipient, has built a career on making unlikely, unconventional scientific connections.
His work could lead to significant medical advances, with clinical trials beginning this year. The work is supported by top national granting organisations and the United States Army, with the goal of assisting soldiers in combat. Colleagues laud his distinct approach, with one calling his work “seminal.”
“I want to make miracles happen more often,” Roth says of his motivation for medical research. [This Scientist Is Searching For Secrets Of Life]
Many years ago, Roth became intrigued by reports of people who went into suspended animation as a result of extreme conditions and were later revived despite appearing to be dead. However, the occurrence of frozen misadventures and stowaways is too rare to warrant a research investigation. As a result, he took a different approach. He began studying people who had experienced extreme stress: heart attacks, trauma, sepsis (a deadly condition caused by massive infections), and now COVID-19 cases.
“We study people who have, if you will, near-death experiences, and then we try to understand what they’re doing and how that relates to whether they survive or not,” Roth explained.
He was on the hunt for the biological elixir that kept people alive in the most dire of circumstances.
A necessary component for reanimation [This Scientist Is Searching For Secrets Of Life]
Roth began with animal studies in which he attempted to mimic these states of animation. He discovered that by reducing their oxygen demand, he could de-animate and re-animate creatures ranging from worms and zebrafish to mice. He accomplished this by increasing their sulphide and selenide levels, which are naturally occurring substances that we eat or breathe and are essential to life at low levels.
“You buy time for repair” when you induce suspended animation in an injured person or animal, according to Peter Radermacher, professor of Anesthesiology and Intensive Care Medicine at University Medical School in Ulm, Germany.
Radermacher remembered seeing Roth’s research on mice and sulphide, which he used in the form of hydrogen sulphide, back in 2005. “It was a seminal paper,” he said of the paper. “It used hydrogen sulphide to launch thousands of papers.” [This Scientist Is Searching For Secrets Of Life]
Roth founded Ikaria the same year to develop hydrogen sulfide-based treatments for humans. Mallinckrodt Pharmaceuticals of the United Kingdom purchased the company for $2.3 billion, but the biotech company stopped researching Roth’s sulfur-based de-animating therapeutics a few years later.
At higher concentrations, sulphide is lethal, and some researchers questioned whether hydrogen sulphide treatment would work in larger mammals.
So Roth turned to bromide and iodide, elements on the periodic table that are close cousins to sulphide and selenide. Bromide had already been used in medicine as a sedative, inducing de-animation, since the 1800s. He wondered if our bodies could use these elements differently in traumatic situations than they do in normal conditions to help us survive.
“When you have a severe event, you either redistribute them properly, in which case you can get into your sleeping bag and survive that near-death moment, in other words, de-animate properly and then you can be reanimated,” Roth explained. [This Scientist Is Searching For Secrets Of Life]
“So, what exactly are those redistribution events? “Can you define them for me?” he inquired. “And can you augment them to make it so that people who would have been dead are now not dead? That is the intention.”
He discovered a significant increase in iodide levels in blood collected from trauma or sepsis patients. But the presence of iodide in the blood did not reveal what it was doing — was it helping or harming?
So Roth and his colleagues turned to animal models, where they discovered that increasing iodide levels in mice, pigs, and rats resulted in better outcomes when subjected to traumatic events when compared to those who did not receive the treatment. [This Scientist Is Searching For Secrets Of Life]
The advantages are due to some basic chemistry. In the case of a heart attack, for example, blood flow is disrupted, depriving the heart muscle of oxygen. It turns off or de-animates. When oxygen returns, however, there is an excess of it, and hydrogen peroxide is produced. In turn, the hydrogen peroxide wreaks havoc on healthy tissue, killing it. Iodide can act as a shield by chemically converting hydrogen peroxide into oxygen and water, thereby reducing inflammation. Damage has been avoided. A successful reanimation.
Dr. Sam Tisherman, a professor of surgery at the University of Maryland School of Medicine, studies “therapeutic hypothermia” as a treatment for trauma and cardiac patients. The cold temperature slows metabolism, giving surgeons more time to perform surgery.
“At some point, you have to give oxygen back, but how can you avoid the oxidative burst damage?” Tisherman explained. Roth’s approach could be beneficial. “If it could work,” he said, “that would be complementary.” [This Scientist Is Searching For Secrets Of Life]
The iodide relationship
It all added up for Roth. Iodide was not only a cellular superhero in humans, but it also played a stress response role in a variety of organisms.
“The phenomenon of redistribution of these elements during stressful situations is not unique to people,” he explained. “It is widespread in biology.”
Take, for example, Arctic ground squirrels in Alaska. Researchers working with Roth were able to simulate the squirrels’ normal winter hibernation in a lab setting. They took blood samples from sleeping versus frolicking rodents. Iodide levels in hibernating squirrels’ blood were two to three times higher than in normally active squirrels. Roth believes that the increased iodide helps the rodents safely recover from their suspended animation state. [This Scientist Is Searching For Secrets Of Life]
Another example is a brown algae known in the Pacific Northwest as the massive bull kelp, which can be found near beaches with its rubbery ribbons. The nearshore plant has some of the highest concentrations of iodide of any organism. As the tides rise and fall, the kelp is exposed to sunlight and air, which produce harmful hydrogen peroxide. Iodide can once again limit the peroxide’s toxicity.
“What if the key to dramatic survival stories is what people were eating in the days and weeks before the trauma or accident?” Roth wondered.
Roth’s overarching goal has been to apply his research to the field of healthcare. As a result, in 2014, he founded Faraday Pharmaceuticals, a biotech spinoff from Hutch. He currently serves as a board member and consultant for the Seattle-based firm. [This Scientist Is Searching For Secrets Of Life]
Roth and colleagues published research in October showing naturally elevated iodide levels in hibernating squirrels as well as blood drawn from trauma and sepsis patients. The researchers also gave iodide or saline injections to mice that had muscle damage in their hind legs, with the mice given extra iodide showing less damage to muscle tissue.
Scientists from the Hutch, Faraday, the Department of Emergency Medicine at the University of Washington, the Department of Surgery at Seattle’s Harborview Medical Center, and the University of Alaska are among those who contributed to the paper. The study appeared in the journal Critical Care Explorations.
(Dr. Ron Maier, one of the authors, was also the surgeon-in-chief of the team that successfully treated a semi-frozen hiker who was found in November after becoming lost on Rainier.) [This Scientist Is Searching For Secrets Of Life]
Most importantly, the research suggests that iodide could be used to treat human patients as well. Faraday scientists presented findings from a study of 120 patients who had serious heart attacks in 2019. According to Phase 2 study results presented at an American Heart Association meeting, patients who received an iodide-based drug developed by Faraday had less heart damage.
Roth and colleagues will begin another Phase 2 study this year to investigate the effects of providing intravenous iodide to trauma patients.
They will also begin a more rigorous Phase 3 study of heart attack patients and iodide treatment, which will last about two years. If the results are positive, the US Food and Drug Administration will evaluate the treatment for another six months before making it part of routine care. [This Scientist Is Searching For Secrets Of Life]
Roth hopes that his insights into suspended animation will help the critically ill.
The research on squirrels, mice, and humans “suggests that rapid increases in iodide in the blood could represent an ancient stress response that is shared across animals,” according to Roth. “If we can harness this ability, it has the potential to transform emergency medicine.”
