October 4, 2005
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Round-Trip Journeys to the Afterworld
A patient is delivered by helicopter to Berlin’s Accident Hospital: More seriously wounded patients might survive if they were put into a state of suspended animation before they got transported
Medicine
Round-Trip Journeys to the Afterworld
By Jörg Blech
Researchers allow pigs and dogs to bleed to death, fill their bodies with cold saline solution, and then bring the dead animals back to life a few hours later. The ability to switch living beings off and then on again could revolutionize medicine — especially treatment of bleeding victims or heart-attack patients.
First the heart begins to beat, and then the pig starts breathing. Finally, it stands up and looks curiously at the man in the lab coat standing outside its cage.
“This animal was dead for several hours,” says Hasan Alam, 39, a surgeon at Boston’s Massachusetts General Hospital. “But we brought it back. And now it’s here again.”
The same magic forces seem to be at work in the animal research facility of the General Hospital of the City of Vienna. Pigs are suddenly opening their eyes after their hearts were stopped with electric shocks and they lay dead for half an hour. “The miracle,” says Wilhelm Behringer, 39, a physician specializing in emergency medicine, “is that the animals return to life without neurological damage.”
In the last few years, the two research groups have sent a hundred pigs on round-trip journeys into the afterworld, using variations on the same trick in each case. The physicians flood the animals’ bodies with several liters of a saline solution that’s been cooled to about two degrees C (36° F). This puts the animals into a mysterious state of suspended animation that prevents the cells of their lifeless bodies from dying off. None of the animals feel pain, because the experiments are done under full anesthesia.
Until now, we’ve left it to science fiction writers to describe what it might be like to take a break from life and then return at some point in the future. Only in science fiction can an astronaut sink into a Rip van Winkle-like sleep that lasts centuries, only to wake up — wrinkle-free — in some distant time or galaxy. And only in science fiction can people with incurable diseases have themselves placed into suspended animation until science catches up and discovers a cure.
Dozens of people have felt such a tremendous yearning for a second life that they spent a lot of money to have their bodies frozen in liquid nitrogen after death. Awaiting resurrection, their heads and bodies float in tanks in Arizona and California operated by companies that specialize in this practice.
The spectacular animal experiments performed in Boston and Vienna make these utopias seem not quite so bizarre. The researchers don’t talk in terms of years, but they’re convinced — for the first time — that sending humans into an hours-long deathly sleep will be possible.
“It may sound futuristic, but we now have the ability to deliberately bring the body to a standstill,” explains Hasan Alam, who recently moved his laboratory from Maryland to Massachusetts so that he could take advantage of fresh research funding to move ahead with his project.
Alam hasn’t even unpacked his moving boxes yet. Instead, he prefers to sit in his corner office, wearing a dark blue suit, interviewing the kinds of ambitious doctors and scientists he needs to work on his project.
“We are preparing initial clinical trials with human beings,” explains Alam. He isn’t the only one conducting this kind of research. In hospitals in Pittsburgh, Baltimore, Los Angeles and Houston, other doctors are pursuing similar plans to essentially switch off the human body and then switch it on again. The data from these experiments will then be included in a joint analysis.
The candidates Professor Alam envisions for these trips to death and back are people who are admitted to emergency rooms with the most serious of gunshot wounds or injuries from accidents. Although their wounds may be relatively easy to suture, “surgeons need time,” says Alam. He says that 19 of such patients out of 20 bleed to death before emergency doctors can finish their work.
But, as Alam and his associates hope, deliberately placing the dying bodies into a state of suspended animation can provide precious time needed to bring the victims to the hospital and perform surgery.
This is the scenario they envision: Instead of following the usual procedure of pumping banked blood into a trauma patient, emergency physicians allow the patient to bleed to death within minutes while recapturing the patient’s blood. At the same time, the patient is quickly filled up with a cold saline solution. Only when his wounds have been sutured is the patient revived by returning his own warm blood to his veins and arteries.
The Boston group plans to try this procedure in human subjects within the next 12 to 18 months. Hasan Alam believes the relevant ethics commission will approve his request, because the first of these experiments would be performed on injured patients who normally couldn’t be saved with conventional emergency medicine.
The idea that in certain situations it can be a good idea to refrigerate a human being goes back to Peter Safar, a doctor who was born in Vienna and died in 2003, at the age of 79. Safar was interested in developing a new method of emergency medical care for the US military. In the Vietnam War, many GIs suffered serious wounds in battle and lost so much blood that they went into cardiac arrest. But with a little more time, many could have been taken to field hospitals and stitched back together.
At the University of Pittsburgh, Safar sent dogs into a state he called “suspended animation.” To do this, he allowed the dogs to bleed to death and then flushed ice-cold saline solution into their aortas through a tube (at a rate of one to two liters a minute). Within a few minutes, the dogs’ body temperatures plunged to 10° C (50° F). The pallid canines were dead, at least according to the laws of medicine: no heartbeat, no breathing, no brain activity.
The dogs’ blood was collected, kept warm, enriched with oxygen and later pumped back into their bodies. Then the white-haired professor used mild electric shocks to bring the lifeless creatures back to life. After Safar’s death, his colleagues fine-tuned the process by adding tiny amounts of sugar to the cold saline solution. This, the Pittsburgh researchers announced in June, enables them to revive the dogs after as long as three hours.
In other experiments, scientists have already shown that the principle of suspended animation could revolutionize emergency medicine. Professor Behringer’s research team in Vienna, for example, has focused its research efforts on saving people who collapse after a heart attack and then often die of cardiac failure. The Vienna researchers have replicated this process in animal experiments. Pigs are fully anesthetized and then given an electric shock to the chest, stopping the heart and replicating a heart attack.
After 15 minutes of complete cardiac arrest and 20 minutes of resuscitation using such conventional methods as heart compression massage, electroshocks and medication, the Viennese are able to revive very few of these pigs. And those that do make it end up having severe neurological damage.
The results are vastly superior when the researchers, before attempting resuscitation, flush three liters of saline solution into the main arteries of the lifeless pigs, thereby deliberately cooling down the brain and heart (in contrast to the experiments in Boston, these animals are not allowed to bleed to death). After a 20-minute waiting period — simulating the time it might take to transport a trauma patient to a hospital emergency room — the animals are connected to a heart-lung machine, reanimated, and then, using medication and ice cubes, kept in a recuperative state of semi-narcosis at a body temperature of 33° C (91.4° F) for 24 hours. Only then, says Behringer, are they “permitted to wake up again.” Eighty-five percent of the pigs wake up, without significant consequential damage.
Hasan Alam’s group, whose research is directed at saving people who would normally bleed to death, has reported similar results. In their experiments, the scientists used scalpels to inflict potentially fatal injuries on the pigs, then waited half an hour before beginning to suture the wounds. All the animals that received no cooling fluid died. Other pigs were quickly cooled from a body temperature of 37°C (98.6° F) to 10° C (50° F) in 28 minutes. Eighty-seven percent of these animals were saved with emergency surgery and revived after more than an hour.
The surviving pigs were given behavioral tests, which they passed with flying colors. They were able to find hidden raisins and apples just as effectively as normal control animals. Analyses of their brain tissue revealed that the pigs had survived their death-excursions without neurological damage.
All of this seems incompatible with the rules of biology. Until now it was considered incontrovertible that the brain will if it’s deprived of oxygen for only a few minutes (four to five minutes in human beings). Heart cells and other tissue are also irreversibly destroyed if the oxygen supply drops below a critical level.
But it seems the shock of cold temperature can interrupt these processes. For every 10° C (18° F) drop in human body temperature, the metabolic rate drops by 50 percent. This reduction also slows down the process of dying, explains Hasan Alam. At a body temperature of 30°C (86° F), the brain can survive without oxygen for 20 minutes. Decrease the temperature to 10° C (50° F) and the brain can survive for as long as 90 to 120 minutes.
This phenomenon explains those legendary cases in which people have survived extremely long periods of oxygen deficiency. In the spring of 2000, for example, a three-year-old girl in a stroller rolled down an embankment and sank into the cold water of the Neckar River in southern Germany. The water temperature was 10° C (50° F). Even though the girl was under water for 45 minutes, emergency personnel were able to revive her. Scientists also know that heart attack patients’ chances of survival increase when their bodies are cooled.
Researchers don’t understand the details of why cold temperatures protect the body against death. They do know that metabolism continues in the body’s cells for a short period of time after a person is already dead; but the remaining oxygen in the blood is no longer sufficient to produce energy. Instead, the cellular respiratory chain produces toxic free oxygen radicals at a higher rate than normal, killing the cells. In other words, the cellular metabolism continuing in a cell after death is in fact the cell’s own downfall.
Apparently, the cool saline solution puts a stop to this process. First, the cold temperature dramatically reduces metabolic activity. Second, the solution completely flushes the blood and, along with it, the remaining oxygen out of the body tissue. There is nothing left to fuel the respiratory chain, and free radicals can no longer be produced to kill off the cells. The result? The body glides into a state of suspended animation.
Using the same logic, this sleep of death should also set in if cell respiration is interrupted by other means. This is precisely what 47-year-old cell biologist Mark Roth of the University of Washington in Seattle has demonstrated in a series of elegant experiments. To conduct the experiments, he used gases like carbon monoxide and hydrogen sulfide, which interfere in oxygen-consuming metabolic processes, binding to the same proteins and enzymes in the body and thus destroying cellular respiration.
When Roth administered a gaseous mixture of hydrogen sulfide and normal air to laboratory mice, the animals sank into an artificial hibernation. Their heart rates declined from 120 to 10 beats per minute. Their body temperatures dropped from 37° C (98.6° F) to as little as 15° C (59° F), which was slightly higher than the temperature in the room. After six hours, their metabolic rate had dropped by 90 percent. The resuscitation of these deep sleepers was remarkably simple. After being kept in fresh air and at normal room temperature, the mice woke up on their own and were as healthy as before. Roth plans to repeat his experiments with larger animals, and is ultimately aiming for human tests.
Just how long these excursions into the afterworld can be drawn out remains unknown. In any case, no one is likely to be booking trips to faraway galaxies anytime soon. It may be that the records achieved so far — three hours in dogs and six hours in mice — already represent the upper limit.
Freezing entire bodies in liquid nitrogen is not an alternative. In fact, scientists are now convinced that this approach is mistaken. Although human metabolism comes to an abrupt halt at -196° C (-320° F), ice crystals forming in the cells at this temperature destroy the tissue.
Of course, this discovery comes a bit late for those trusting souls who had their remains put to rest in nitrogen. “All those whose bodies were deliberately frozen,” says Viennese physician and scientist Behringer, “will never be thawed and brought back to life.”
Translated from the German by Christopher Sultan
