Cheating Death

by Sanjay Gupta

  Kellum says that when he first started telling people about his results, he was met with stark disbelief. At one point, he flew to Kansas City to give a presentation about CCR to a medical group. Afterward, Kellum says, “The top three people went out to dinner and said, ‘That guy is certifiably insane.’ And then they began to look at the data, and you just can’t argue with it.”

  By tripling the survival rate from cardiac arrest in Arizona, Bobrow estimates his paramedics saved several hundred lives during the three-year study period alone. A medicine that did the same would be a best seller. “It’s a phenomenal thing,” Bobrow told me. “Here you have a situation where not one nickel has been spent teaching this, and it turns out to be just as good—or in my view, better—than something on which millions of dollars and man-hours have been spent.”

  In the world of medicine, paradoxically, it can be much harder to convince people to try a simple and inexpensive solution than one that is complex and unproven. Here’s my own theory: There are thousands of medical journals churning out new articles every week. Sorting the useful from the useless is a herculean task. Meanwhile, there are approximately 800,000 physicians in the United States, most of whom aren’t leafing through medical journals in their spare time. In that sea of information, a new idea or therapy, even one that’s a proven success, has to struggle to capture attention. A company with a new wonder drug is often willing to spend millions or even billions of dollars to tell physicians about its benefits. On the other hand, something as basic as a new kind of CPR—well, who’s got a stake in that? 22

  ON A FEBRUARY day in 2008, in the mellow afternoon glow of the Arizona winter, Mike Mertz grinned from ear to ear as he walked into Glendale Fire Station 154. He wanted to shake hands with Ruben Florez and the rest of the crew that saved his life. Bentley Bobrow was there, too, shaking his head: “He truly was dead, and here he is, fine.”

  In medicine, there’s often a choice between pursuing the known course, the comfortable course, the well-worn path—and trying something new. Innovation might save lives and yet at the same time cost lives. Medicine in general is geared toward caution. First, do no harm. And yet, our greatest learning comes not from never failing, but in learning from our mistakes, rising up every time we do fail.

  The smiles lasted a few minutes, until a call came in and Florez and the engine had to pull out. Afterward, in the quiet outside the station, Mertz wondered aloud at the other path he might have taken. When he came in to the hospital, doctors had told his daughter that he most likely wasn’t going to make it. “I was completely out. Gone,” he said. “If that UPS guy hadn’t come around the corner, I wouldn’t be here today. It was that close.”

  Even more than that, if it weren’t for the persistent efforts of brave physicians like Gordon Ewy, Mike Mertz probably wouldn’t be standing there outside the fire station. He wouldn’t have a newly implanted defibrillator, and he wouldn’t be looking forward to getting back on the golf course. Just six weeks after he died, the only lingering effect is a set of sore ribs.

  Mertz probably owes his life to a handful of physicians who were willing to challenge the rules, if not quite break them. And when the doctors say there was nothing to lose, they have a point. Basic artificial respiration has been around since the 1700s, and the modern technique has been in use for half a century. But a dirty little secret remains: most of the time, it doesn’t work. In most cities, “survival to good outcome” for cardiac arrest outside the hospital is still around 2 percent, and in some places, it’s even worse. In Detroit during a six-month period in 2002, paramedics responded to more than four hundred cardiac arrest cases and emerged with just a single success story—one patient who survived long enough to make it out of the hospital. 23

  Yet other places seem to have cracked the code. Arizona tripled the survival rate of cardiac arrests. Seattle, with its high percentage of trained bystanders and tradition of innovation in emergency medicine, reports a survival rate of close to 20 percent—and nearly 40 percent in cases where paramedics find a patient whose heart is in ventricular fibrillation, the most “survivable” rhythm. 24 Like Arizona, Seattle now uses a resuscitation method that emphasizes chest compressions. Seattle does something else that’s interesting; officials take care not to hire too many EMTs. They’ve found that when they hired too many people, each EMT got less practice and survival rates dropped. 25

  None of this is rocket science or brain surgery. The closer you look, the more you see that it doesn’t always require a fancy breakthrough to save tens of thousands of lives. When it comes to cheating death, it sometimes happens that simple measures are more important than the hoops and frills of high-tech medicine. Sometimes a sea change in the world of medicine can be accomplished by lucky accident and the efforts of a few individuals who refuse to accept the conventional wisdom.

  CHAPTER THREE

  Suspend Disbelief

  When does death really take place? I would argue that we don’t really know the answer.

  —Dr. Lance Becker

  ASOLDIER FALLS IN a gully, off a long mountain pass near Khost, Afghanistan, after being hit by sniper fire. His comrades scatter for cover, scanning the hillsides for the sniper. Seeing no target, they let loose with a heavy machine gun to provide cover while a medic tries to reach the fallen man. There’s no panic, but there is urgency. The medic tears through his pack, fingers pulling apart the edges of a small syringe. With heavy breaths, he counts off, “One, two, three…” then races across the open ground while his friends lay a withering burst of fire in the general direction of the sniper’s position.

  When the corporal reaches the fallen man, he feels for a pulse, but the one he finds is so weak that he knows it won’t last more than a few minutes. The platoon is dozens of miles from help, and even a helicopter couldn’t arrive in time to save the injured soldier. Gritting his teeth, the medic saws open the unconscious man’s field jacket and cuts away his trousers. There’s the sound of more gunfire not far off. It looks like the soldiers might be stuck here for a while.

  With a grunt, the medic jabs his syringe into the thigh of his fallen comrade. The effect is immediate. The soldier’s skin, already pale, turns gray and then white within seconds. His skin grows cold and dry. Breathing goes silent, and the pulse goes still. But the medic isn’t alarmed. He knows his friend will probably be fine. He isn’t dead; he’s merely preserved in a safe cocoon. Call it suspended animation, slow motion, a pause button—whatever. As long as the patrol can hold off the bands of Taliban for a few more hours, there will be plenty of time to wait for the lifesaving helicopter from Bagram Air Base.

  This scenario has never actually happened, but it may be closer than you think. The picture was painted for us by officials from the Defense Advanced Research Projects Agency (DARPA), a military office devoted to exploring technological breakthroughs. DARPA funds some of the most cutting-edge medical research on the planet. If you want to think of ways to truly snatch life from the jaws of death, this is a good place to start.

  WHEN I ASKED DARPA officials about cheating death, I ended up in a spot that’s about as far from Afghanistan as you can get, walking past luxury speedboats docked along Fairview Avenue, collar turned up against the unseasonably cold Seattle day. The city was bracing for a rare snowstorm. The Space Needle rising up behind us seemed to touch the low gray clouds, and next to it, the wild red and silver curves of the Science Fiction Museum. Turning in from the waterfront, we were on the campus of the Fred Hutchinson Cancer Research Center, five brick-and-glass buildings sitting at the base of a steep hill, tucked between the water and a concrete overpass.

  On a wall of the narrow, tastefully decorated lobby sat three plaques framed in glass. These are the Nobel Prizes awarded to researchers at “the Hutch.” I thought it was pretty cool, but most of the people in the lobby walked by without a glimpse. I realized this was a place where breakthroughs are expected.

  I was here at the Hutch because I wanted a glimpse of what
could be the biggest medical breakthrough ever—-a way to stop death in its tracks. As we crowded around a glass hood in a lab room upstairs, we looked at the unwitting subject of the day’s experiment: a furry white rat, all quick movements, trapped in a glass enclosure, his bright red eyes staring back at us with a hint of curiosity.

  A scientist named Mark Roth also peered at the rat, his eyes squinting under a tall forehead and an unruly patch of thinning red hair. A younger colleague, Jennifer Blackwood, casual in the running clothes she wore to work, checked the gear for the experiment. Roth gave her a nod, Blackwood turned a dial, and the rat’s enclosure began to fill with deadly hydrogen sulfide gas. “He has no clue,” she said. The gas is invisible, but we know it’s there because the rat is suddenly at attention, nose upturned and furiously sniffing at the air.

  Hydrogen sulfide is the chemical that gives rotting eggs such a strong smell. An ounce could kill dozens of people. 1 At a concentration of five hundred parts per million, it’s about four times as toxic as carbon monoxide, 2 but the rat doesn’t seem too alarmed. For several seconds, he just keeps sniffing. On a monitor next to the enclosure, though, we can see things changing. The monitor measures the rat’s output of carbon dioxide—his breathing, his metabolism. And the line is going down. Basically, Dr. Roth is turning off the rat. Not all the way, mind you—but pretty far down, like turning down the lights with a dimmer switch. Two minutes in and the rat is barely moving, just staring straight ahead. He’s not quite frozen, but everything about him is going in extreme slow motion.

  When Roth does this experiment for real, he can keep the rat in this state for six hours. He could probably do it even longer, but that’s when he turned the experiment off. “We proved our point” is how he put it to me. We won’t be around six hours later, so after about ten minutes, Blackwood turns the dial the other way, flushing the hydrogen sulfide from the rat’s enclosure and replacing it with oxygen. The dimmer switch comes back up. The rat starts to move. Five minutes later, the rat is wiggling around like nothing ever happened.

  Dr. Roth makes an unlikely mad scientist, with his easy smile, blue Converse sneakers, and a pullover shirt left over from his daily commute—a four-mile jog. His idea of a fun night is to sit home watching movies with his wife, teenage daughter, and ten-year-old son. 3 When the first lab mouse came back from a dose of hydrogen sulfide, Roth’s first move wasn’t to call DARPA or the NIH—it was rounding up everyone in the lab and going across the street for a beer. A Xeroxed picture of “the beer mouse” is still on the wall, along with oddball stickers and articles, like one about a guy who kept his wife in a freezer for six years after she died of cancer. But make no mistake: There is big stuff going on here. Maybe Nobel Prize–type stuff. It has already gotten Roth a so-called genius fellowship from the MacArthur Foundation. 4

  You see, the amazing thing isn’t that you can fiddle with the dimmer switch on these lab rats and mice, it’s what you can do while the lights are almost out. To come up with a pause button for death—something that would really help those soldiers in Afghanistan—you need to do some gruesome stuff. You need to mimic the wounds that a soldier might suffer from a bullet or explosion, and you have to drain the blood from your lab animals, let them die—or come close—and then find a way to put them back together. When you drain the blood from lab mice and leave them for six hours, there’s no way to bring them back. When Roth did the same thing after knocking them out with hydrogen sulfide, well, it was another story. The mice were all brought back, and they all woke up. There was nothing wrong with them.

  As you might imagine, the team at DARPA is pretty excited about this. 5 And so are a lot of other people. After the first experiments, Roth founded a private company, Ikaria, to turn the poison gas into medical therapies. By the time it merged with a larger company in 2007, the business was valued at $670 million. 6

  Asked what drives him, Roth chuckles. Then he says it’s simple: people die, and they don’t want to. “We’re trying to extend survival. If you go to most physicians, they say, ‘Time of death is whatever,’ and you ask, ‘Why did he die?’ A lot of physicians will say it’s because of a failure to perfuse tissues with enough oxygen. Whether it’s cardiac arrest or cancer, it’s the inability of blood to get to some essential organ,” said Roth. “Is it true? Well, I don’t know. I don’t know why anyone ever dies. I think about it a lot.”

  Roth raises an essential question, the essential question: whether it’s a gunshot wound or cancer, drowning or a heart attack, what do the endgames have in common? In theory, the damage from almost any injury or illness could be repaired given enough time. Massive wounds can be pieced together, and even hearts can be replaced.

  It’s all about time. When the heart misses a beat, an hourglass starts running. Up to now, we’ve been measuring time in seconds and minutes, an hour or two at most. CPR might stop the falling sand for a few minutes. Zeyad Barazanji and Mike Mertz are alive because someone used those precious minutes to pump on their chests, keeping blood and oxygen going to their vital organs. Anna Bagenholm got an extra three hours. She’s alive because she was doused in a freezing stream, and her metabolism slowed enough that there was time to get her to a hospital before too many cells inside her brain and heart could die.

  Seconds, minutes, hours. Sure, these are great achievements in a crisis where every second counts, but let’s use our imagination to take a step further, to see if we could stop the sands of the hourglass entirely—or at least slow them to an imperceptible trickle. There are a handful of tantalizing examples, which suggest there might be a way to do just that.

  One especially dramatic story of survival belongs to a thirty-five-year-old man named Mitsutaka Uchikoshi from Nishinomiya, Japan. One afternoon in October 2006, he joined colleagues from the city office for an afternoon of hiking and grilling out on Rokko mountain, part of a park near the city of Kobe. After the meal, Uchikoshi decided to walk down alone; unfortunately, he fell, struck his head on a rock, and lay undiscovered on the side of the mountain for twenty-four days. By the time he was found, he was unconscious, with an extremely faint pulse. Most of his organs weren’t functioning, and his body temperature was just 71 degrees.

  But within just a few hours of being taken to Kobe City General Hospital, he woke up, and a few weeks after that, Uchikoshi went home. At a press conference at the hospital, before checking out, Uchikoshi told reporters he had stayed calm throughout the whole ordeal. “On the second day, the sun was out, I was in a field, and I felt very comfortable. That’s my last memory.” 7 He’d been unconscious, lying in a field with no food or water, for more than three weeks. He’d survived a serious head injury, presumably from landing on a rock when he stumbled over the embankment. He’d survived massive blood loss and severe hypothermia. And in the end, he was just fine.

  People like Uchikoshi teach us that the human body can survive far more and far longer than we usually bargain for. The question is, can we harness this remarkable resilience? Can we find a way to manipulate that survival mode, to use it to our advantage, in the ER?

  In the first chapters, I talked about death as a process, an ongoing chain of events that might be reversed with the right intervention. It turns out death is generally caused not directly by lack of oxygen, but by a punishing cascade of chemical reactions triggered by its absence and ultimately by its return. Lance Becker, the director of the Center for Resuscitation Science, told me, “We used to think that once the heart is restarted, our work is done. Once you’re out of cardiac arrest, it’s back to business as usual. But now we know that it kicks off a whole bunch of general mischief, both in the individual cells of the body and in the system as a whole.”

  The mischief creeps in as the minutes pass without oxygen. Cells switch to an ancient backup system: anaerobic metabolism. Chemistry buffs know it as a form of fermentation. And then something dangerous begins to happen in the mitochondria, the part of the cell that produces its energy. Becker’s colleague, Dr. Ben Abella, say
s, “You can make an analogy to nuclear power plants. In a nuke plant, stopping production altogether is a dangerous process. So there are control rods that keep it firing at a low, controlled burn. For some reason not well understood, when we stop blood flow and deprive the mitochondria of oxygen, we start to lose the control rods.”

  You might be surprised to learn that it gets even worse when oxygen is returned to the mix—for example, after a successful resuscitation. “It’s a time bomb,” says Abella. “When oxygen comes rushing back, the control rods are missing. It goes nuts.” The resulting damage, from the addition of oxygen to the mix, is known as reperfusion injury. The reintroduction of oxygen leads to the production of a variety of toxic compounds, including free radicals and a variety of proteins, such as cytochrome c, which triggers a type of preprogrammed cell death known as apoptosis. 8

  Every cell in our body is coded with instructions for apoptosis. While it may seem counterintuitive, not to mention counterproductive, under most circumstances cell death is a beneficial, even necessary process. As we constantly grow new cells, the old ones have to go. When apoptosis malfunctions, the result is disastrous, uncontrolled growth: cancer.

  Unfortunately, in the oxygen-generated chaos of reperfusion injury, apoptosis is a killer. This chain reaction—hard to stop once it gets going—has caused much frustration over the years for doctors and paramedics. They could revive patients who had been clinically dead for as long as an hour, but just getting back the heartbeat wasn’t enough. The vast majority of these patients came back without meaningful brain function. They might as well have stayed dead.