A mechanical ventilator at Massachusetts General Hospital is
used by trauma surgeons to revive pigs from
a state of suspended animation.
Photo courtesy of Alex Stone
Alam admits to being awed by his seemingly miraculous ability to resuscitate the animals. “There have been seven different studies, and they’ve all been successful,” he says. “In injuries that would ordinarily be fatal, I can save the animals over 90 percent of the time.” Yet the science underlying this miracle is rather straightforward. In essence, suspended animation is an exercise in basic economics at the biological level. Life demands oxygen, and without enough of it the body dies. In the case of severe trauma—from massive blood loss, say—oxygen supply falls while demand remains high. When deprived of oxygen, the average person will suffer brain damage within 5 minutes, and death follows in another 15 minutes.
Cooling the body is a way to restore the balance between oxygen supply and demand by slowing metabolic activity and thus curtailing oxygen needs until the supply can return to baseline. Low temperatures have long been known to depress the body’s metabolic rate. Organs intended for transplant are stored on ice during transport—a stopped heart can be preserved this way for up to four hours—and neurosurgeons routinely cool the brains of stroke patients during surgery to minimize damage. Alam’s team and the Safar group have shown how to extend this concept to the whole organism.
The crucial next step is to test suspended animation in humans, and Alam has teamed up with the Safar group to design a clinical trial that will bring the procedure to hospitals in the United States. Informed consent is by far the thorniest issue because the procedure can be tested only on people who are mortally wounded. “When a person is bleeding to death, it is not an appropriate time to get them to sign forms,” Alam says. To have a meaningful test sample, the researchers would therefore need to obtain pro forma compliance from all (or at least a substantial fraction) of the residents of a host city. That would require an extensive public education campaign—“a challenging undertaking,” Alam admits, but not an impossible one; other researchers have cleared similar hurdles for trials of blood substitutes.
An alternate and even more outlandish approach to suspended animation involves not cooling the body but poisoning it, a tactic being pursued by molecular biologist Mark Roth and his colleagues at the Fred Hutchinson Cancer Research Center in Seattle. A tour of his lab—a space crammed with ventilated walk-in fume hoods, state-of-the-art security sensors, hoses, flasks of bubbling water, and a network of metal tubes—quickly reveals why so few scientists do this sort of research. His facility houses tanks containing some of the world’s most toxic gases—cyanide, phosphine, carbon monoxide, hydrogen sulfide—hermetically sealed inside computer-controlled glass cabinets. “These are very, very toxic to humans and would kill them immediately,” Roth warns.
Broadly speaking, Roth’s work taps into the same biological tricks that the Safar and Alam teams exploit, though in a distinctly different way. For Roth, the key is not to induce hypothermia but to provoke a state resembling hibernation. Hibernating animals drastically reduce their metabolic rates and thus their need for oxygen. Conversely, by depriving his experimental subjects of oxygen, Roth reasoned he could put them into an artificial state of hibernation. Early results in the roundworm Caenorhabditis elegans, reported by Roth in 2004, bolstered this notion. He found that placing the worms in an atmosphere with an oxygen concentration of just .001 percent or less triggers a condition in which all of their biological activity shuts down for up to two days. By contrast, the worms normally suffocate at a far less austere oxygen concentration of .1 percent; ordinary room air is 21 percent oxygen.
At the heart of this paradox is a process called oxidative phosphorylation, by which cells produce energy. Cells require oxygen to make molecules of adenosine triphosphate, or ATP, the primary fuel of life. When oxygen falls below an optimal level, energy production goes haywire, and destructive molecular fragments known as free radicals are released instead. Roth’s term for this fatal middle zone is evil oxygen tension. But in a world almost completely devoid of oxygen, oxidative phosphorylation stops, and the animal simply rests. “This is something we hadn’t expected,” he says. “If you have some oxygen, you’re dead. But if I take away that little bit of rope you’re using to hang yourself, then you’re alive again.”
Roth set out to find a means to induce oxygen deprivation while bypassing evil oxygen tension. One day he recalled a documentary he had seen about a Mexican cave system with extremely high levels of hydrogen sulfide, a toxic gas that smells like rotten eggs. Without a respirator, anyone entering the cave would fall unconscious after one breath and die within a few minutes. But during those few minutes, he hypothesized, they would enter a trance similar to that of the roundworms. To test his theory, Roth tried hydrogen sulfide on brown lab mice and was stunned by the outcome. Under the influence of the gas, the animals experienced a precipitous drop in respiration—down to four breaths per minute—and consumed only one-tenth as much oxygen as usual. The mice could linger in this Zen-like stasis for hours before the air was turned back on and were normal in every respect when they finally woke up.
