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Bringing Back the Dead

Dr. Frankenstein may have been ahead of his time. While the good doctor’s strategies for giving life to non-living matter may be far-fetched (electrical currents, combined with ornate chemistry sets), his dream of reanimating the dead is very much still with us today, both in science fiction and real science.

The latest fictional account comes with this week’s release of The Lazarus Effect, which stars Mark Duplass and Olivia Wilde as scientists who develop a special serum to revive the dead. But like Dr. Frankenstein, the two young researchers find that their scientific success comes with horrible consequences.

That’s not the case with Dr. Benjamin S. Abella, Associate Professor of Emergency Medicine at The Hospital of the University of Pennsylvania, Dr. Abella studies sudden cardiac arrest, a leading cause of death, and his pioneering work in therapeutic hypothermia has shown effective new ways of resuscitating the recently deceased. Sloan Science and Film spoke with Dr. Abella about suspended animation, CPR, and how many minutes someone can be dead and still make it back alive.

Sloan Science and Film: What’s the difference between resuscitation or rejuvenation and reanimation?

Benjamin S. Abella: Rejuvenation isn’t really a scientific term we use, presuming you’re saying it as something that relates to bringing back the dead or raising the dead. Resuscitation is a scientific term, which relates to bringing back to life the freshly dead. When someone’s heart stops beating, it’s cardiac arrest. And it’s one of the leading causes of death in the United States. It kills as many as 300,000 Americans each year and survival rates are quite poor.

It’s important to note that resuscitation relates to people who have just had their heart stopped. So technically we would call that dead, but the terminology gets a little fuzzy. Certainly if someone has been dead for a long period of time—meaning anywhere over a half-an-hour to an hour—resuscitation in its current terms is unsuccessful or impossible. In popular culture, we see rejuvenation or the “Lazarus effect” of someone who is very dead for quite some time—hours or a day—and brought back to life. We’d love that, but in the current frame of technology and medical options, that’s just not possible.

SSF: What exactly happens to the body after an hour that makes resuscitation essentially impossible?

BA: That’s a very central question, and we really don’t have good answers. One of the least understood areas of the field is what are the injury pathways that make this such a time-sensitive issue. Cardiac arrest is one of the most exquisitely time-sensitive diseases known to medicine. Every minute you’re in unsafe cardiac arrest without CPR or shocks, your survival rate drops 10%. This helps put in context why it’s so mortal. Let’s say someone collapses in your house, and you call an ambulance. Response time might be seven minutes, so already you have lost up to 50-70% of your chance of successful resuscitation. So the question is: What’s going on here? There are a number of things thought to be at play.

One of them is that in each of our cells there is a nuclear power plant called the mitochondria. They generate incredible power for the body, but on the other hand, if they’re not controlled carefully, they can cause immense damage and cell death very quickly. Mitochondria become markedly dysfunctional in the midst of a loss of blood flow, and like you need to keep the electricity at a nuclear power plant on to keep all those control rods and mechanisms in place, the minute you flip that switch off, it can be a big issue. Mitochondria might be the key to the puzzle of life after death.

We don’t have medicine that directly targets mitochondria. We have some candidates. But it’s not primetime. We don’t have medicine that we could inject into people that would restore mitochondrial health. That would be tremendous and it’s certainly an act of investigation.

Another area is injury pathways. The endothelium, which is an inner layer of blood vessels, does a lot of important things. It prevents leaks outside the blood vessels, for example. And it’s clear that endothelial layers become dysfunctional with loss of blood flow. And when blood flow is restored, the endothelium can become leaky and unstable and it’s hard to restore them back to how they were. So those are two areas of research.

SSF: So then how does something like therapeutic hypothermia suspend some of these issues?

BA: That term has become a little outdated; now we use the term targeted temperature management. It’s the idea that you can lower body temperature and control body temperature, which can modulate some of these things. It’s been born out of experiments—when when you cool animals, you can change mitochondrial and endothelial injury, and other things, as well. When you cool animals or humans, you get a lot less brain swelling, which is a very big issue in resuscitation. Some studies show you can almost double survival if you meticulously manage body temperature after cardiac arrest. This is amazing, because it’s not very high-tech, as much as some people might be disappointed to hear that. There are not wild drugs involved; it’s really just cooling blankets. Conceptually, it’s actually very simple.

SSF: How long can someone stay cooled?

BA: The typical protocol is that someone can stay cooling for 24-36 hours following resuscitation. So if you get someone into the hospital, hook the patient up to equipment, and lower their body temperature for about a day, then a number of things are done, and then at a certain point, they’re warmed. Turns out, if someone doesn’t have blood flow for five minutes or more, when blood flow is restored, it takes days to wake up. The brain injury is that profound in just five minutes. And it can be very dramatic, because several days go by with a patient lying there doing nothing, and then all of a sudden, they’ll open their eyes and start to talk. It’s stunning. Family members are blown away. I’ve been in situations where we’ve greeted patients saying, “Welcome back to the land of the living.” And it’s really true.

SSF: What about current experiments we’re seeing now with people who have suffered traumatic blood loss?

BA: Yes. Imagine if somebody bleeds to death in the field, like a soldier in combat. Instead of just resuscitating them right away, they’re cooled to even deeper temperatures, like 15 degrees Centigrade. And then they’re brought back, and then slowly restored and given blood. This is an experimental concept known as suspended animation and it’s being pioneered out of the University of Pittsburgh. This can be very practically important because if someone gets shot and dies, a local field hospital might not have the resources to do a complex resuscitative surgery, so if you can cool the patient and buy yourself an hour, maybe that person could be brought to a more sophisticated central hospital to be resuscitated.

SSF: What do you see as the major misconceptions about resuscitation?

BA: I think one of the most important things is that despite all of the interest in the high-tech stuff and fancy therapies, the fact remains that CPR makes a huge difference in survival rates. It’s an action that any layperson can take, and statistically, it can double or even triple chances of survival from cardiac arrest. So the most important thing is the simplest thing: pushing on the chest to move blood.