SEATTLE, Washington (CNN) -- A wiry, slightly hunched man presses in a few numbers, the electronic lock gives way with a beep and the group presses into the crowded laboratory, plastered with ominous warnings about toxins and biohazards.
Breathing a small amount of toxic hydrogen sulfide gas put this mouse into a state that looked much like death.
Guiding the visitors at the Fred Hutchinson Cancer Research Center is Mark Roth, a 50-year-old biologist with a tall forehead, thinning red hair and a perpetual wry smile. He asks his assistant, Jennifer Blackwood, if the rat is ready. It is. She turns a dial, and the sealed enclosure starts to fill with poison gas -- hydrogen sulfide. An ounce could kill dozens of people.
The rat sniffs the air a few times, and within a minute, his naturally twitchy movements are almost still. On a monitor that shows his rate of breathing, the lines look like a steep mountain slope, going down.
At first glance, that looks bad. We need oxygen to live. If you don't get it for several minutes -- for example, if you suffer cardiac arrest or a bad gunshot wound -- you die. But something else is going on inside this rat. He isn't dead, isn't dying. The reason why, some people think, is the future of emergency medicine.
You see, Roth thinks he's figured out the puzzle. "While it's true we need oxygen to live, it's also a toxin," he explains. Scientists are starting to understand that death isn't caused by oxygen deprivation itself, but by a chain of damaging chemical reactions that are triggered by sharply dropping oxygen levels.
The thing is, those reactions require the presence of some oxygen. Hydrogen sulfide takes the place of oxygen, preventing those reactions from taking place. No chain reaction, no cell death. The patient lives.
Roth's work was inspired in part by personal tragedy. In 1995, his world was turned upside down when his new daughter, Hannah, died after a year of painful medical problems. After that, he decided to go for broke -- to try to tackle something big. "It focuses the mind, when certain things happen to people, and it certainly focused mine."
After that, and after his conceptual breakthrough, Roth was ready to experiment. First up: developing fish embryos. He found a way to drain the oxygen from their cells, and they wouldn't die -- they'd just stop growing. When he put the oxygen back, they'd pick up where they left off. If he suspended them for a day, they took a day longer to develop. No more, no less. Nothing else was different.
Next up were fruit flies. This time, he gassed them. They seemed to die; they stopped moving. Then he returned them to fresh air, and the flies came back to life.
The air we breathe is 21 percent oxygen. At 5 percent, those fish and flies -- like us -- would be dead in a few minutes. At 0.1 percent, it was another story. "You get a state of suspended animation and the creatures do not pass away, and that's the basis of what we see as an alternative way to think about critical care medicine," Roth says. "What you want to do is to have the patient's time slowed down, while everyone around them [like doctors] move at what we would call real time."
If the patient's time -- the process of your death -- were slowed down, doctors would have more time to fix you. In medicine, time is key. An analogy is the history of open heart surgery. For years, surgeons had the technical tools to make simple repairs on the heart, but they couldn't help patients until the development of the heart-lung machine made it possible to preserve the body for more than a few minutes without a heartbeat.
In rolled-up sleeves and blue Converse sneakers, Roth doesn't look the Army type, but by 2001, he had caught the attention of the U.S. military, through the lens of the Defense Advanced Research Projects Agency. DARPA was looking for a way to protect soldiers on the battlefield from death by catastrophic blood loss.
With more than a quarter-million dollars of DARPA money, Roth tried hydrogen sulfide on mice, and it worked. It wasn't quite the same experiment -- he didn't give the mice enough gas to shut down their metabolism entirely, or to kill them, but enough to drop their breathing rate to less than 10 percent of normal. When he reversed the process six hours later, the mice were fine.
That success landed Roth in the pages of Ripley's Believe it or Not, got him a MacArthur Genius Grant and helped him win more than $600 million worth of venture capital funding for Ikaria, the company he co-founded.
But after that, the ride hit a bump. It's been harder than expected to get large animals, like swine, into anything close to suspended animation. Ikaria had to develop an injectable form; the current drug in development is based on sodium sulfide, which dissolves to become hydrogen sulfide in the blood. Trials to test its safety in humans are under way in Canada and Australia.
"[Using hydrogen sulfide] is so simple, it's genius," says David Lefer, a researcher and cardiothoracic surgeon at Emory University, who is now experimenting with hydrogen sulfide in his own lab. "But the failures with larger animals have been a big disappointment. To make this effective for humans may take a combination of sodium sulfide and additional agents. We're just not sure what form it will take."
Animal trials that test sodium sulfide have produced some striking results. Lefer found that it protects mice's hearts during simulated heart attacks. He gave each mouse a dose so small that it was gone from the body 15 minutes later. A full day later, he would induce a heart attack. Subsequent examination found that in the mice that were given sodium sulfide, cells suffered 72 percent less damage than in unprotected mice.
Other researchers are exploring different approaches to tweak metabolism in a critical care setting. A group in Minnesota is developing a drug based on chemicals found in hibernating squirrels. Dr. Philip Bickler, an anesthesiologist at the University of California, San Francisco Medical Center is also studying animals, including whales and dolphins -- mammals like us, except that they can hold their breath for two hours underwater even during vigorous activity. Bickler says, "There's a lot of potential there. It hasn't been studied in extreme detail, but there may be new ways to protect human tissue from injury.The white rat on display in Roth's lab isn't being suspended -- by his description, it's more like a slow-forward button, or a dimmer switch on a light. About 50 minutes after giving the animal a dose of hydrogen sulfide, Roth tells Blackwood to turn off the gas. Normal air flows back into the glass case. The zigzag lines on the monitors shoot upward. In a few minutes, the rat is scurrying around as if nothing had happened.
Roth says he'd be happy to simply develop a drug that can be used in a conventional medical setting. But with a hint of mischief, he admits he doesn't really know how far this could go. Would it work on people? "There are almost certainly reasons it would not, but I don't know what they are yet," he said.
In the meantime, he's having fun trying to change the way we look at life itself. "With those fish, I turn off the heartbeat so they are clinically dead. But I can bring them back. So they must not have been dead, after all."
October 15, 2009
By Caleb Hellerman
CNN Senior Medical Producer