by Rob Dunn
A next major transition in life was the evolution of eaters, species that ate other species. These new life-forms had enzymes—basically chemical knives—that allowed them to digest other cells. Although each was just a single cell in size, they were predators. Suddenly the world had become rougher. Human bodies still use the same genes for many enzymes that these creatures evolved, including those that break down some carbohydrates. Our ability to eat other species, in other words, is a direct consequence of the ability of those ancient single-celled organisms to do the same. Then came the change that set the stage for the origin of hearts.
Three and a half billion years ago, some cells evolved the ability to eat the sun: they photosynthesized.10 The chemistry of the big bang had hamstrung Earth’s denizens, creating a situation in which they had to live off what was left over, the detritus of the universe, but now that species could derive energy from the sun, life itself could add to what was on Earth. Life could even change the atmosphere, albeit without intention or plan. By 2.8 billion years ago, photosynthesizing cells had divided and divided and filled the sea and shallow swamps. They had become so abundant—a green slime of success—that the atmosphere fundamentally changed. It was now full of oxygen, the oxygen that all photosynthetic organisms, be they trees or bacteria, produce as waste when they make sugars out of light’s energy, water, and carbon dioxide. Oxygen was toxic to many species, but microbes can make do, and they did. Some lineages of bacteria evolved the ability to use oxygen in their metabolisms; they did so through a process called respiration. These oxygen-dependent species were the most efficient species that had yet lived (though they could still be damaged by oxygen, just as our modern cells can). They thrived, as did the predators that evolved to eat them. Then something really very unusual happened, a one-of-a-kind event.
For the earliest predators, predation occurred as it does now. Predators found, ate, and digested their prey. But at least once, it did not happen quite that way. A predator consumed an oxygen-loving organism, a single individual of a single species, and that individual, like Jonah inside the belly of the whale, survived. More than that, when the predator reproduced (by dividing), the cell inside it reproduced too, so effectively that each of the descendants of the predator had an oxygen-eater inside it. The predators with the oxygen-eaters inside them, one might imagine, would do worse than those without. But they did not; they did better. They were able to produce more energy from the food they digested because they could use oxygen. As a result, these unusual hybrids thrived.
The success of these hybrids has continued for billions of years. There is one of these oxygen-eaters, in fact, inside every human cell. We now call these oxygen-eaters mitochondria; they are the powerhouses inside cells. All eukaryotes on Earth—including plants, fungi, protists, animals, and many more basic kinds—descend from these chimeras; it was a chimerism that begat success in no small part because it allowed organisms to be more active, to get more energy from one piece of food.
As single-celled organisms evolved into multicellular organisms and, eventually, into all of the multicellular organisms we know today, many things changed. Plants evolved all of the particularities that make them plants (they gained their ability to eat the sun from another ancient coming-together of two lineages, one in which a small photosynthetic bacterium was engulfed but not digested by another organism). Sharks evolved to be sharks, and humans, humans. But through all of this, a mitochondrion—that ancient oxygen-eater—stayed in each cell. New challenges arose as organisms got bigger. In single-celled organisms, oxygen diffuses into the cell from the environment. There is no need for more elaborate contrivances to get oxygen. But as organisms got bigger, oxygen did not diffuse well into those cells farthest from the surface. Branching vessels called tracheae evolved to allow oxygen into the depths of newly evolving bodies. Initially, these organisms had no hearts or contractions of any kind, and they were not filled with blood or even its primitive antecedent. It was enough for the tracheae to make a space through which oxygen could arrive and carbon dioxide could leave.
But there were limits related to the levels of oxygen in the environment. For reasons not yet fully understood, eventually the levels of oxygen in the atmosphere declined. When there was less oxygen, organisms needed to go to greater lengths to find it, and some body types were simply no longer possible. When dragonflies first evolved, for example, the concentration of oxygen in the air was as high as it has ever been. Breathing was easy. The dragonflies, which lack a way of pumping oxygen to their mitochondria, could evolve to enormous sizes—some over two feet wing to wing. But when oxygen levels declined, this type of dragonfly disappeared, never to be seen again. It needed, it would turn out, a heart.
Vessels filled not with air but a liquid—like blood—would be a key first step to getting oxygen around a body. For a body much larger than, say, a roach, blood vessels alone are insufficient to get oxygen to each and every mitochondrion. It was in this context that the heart evolved, first as a sleeve of squeezing cells, then as a small pump, then as a pump with two chambers, and eventually with all of the variety we see among animals. The pump worked to squeeze the oxygen in the blood to each place it needed to go. The lungs evolved to provide greater surface area across which oxygen could be absorbed. And then, when even that was not enough, the body evolved the ability to muscularly inhale and exhale, pulling the universe in with each breath. Once the lungs evolved, blood could carry things other than oxygen and carbon dioxide. It could carry compounds, called hormones, that could signal from one part of the body to another. Blood also came to help stabilize the conditions of cells. A bacterium floating in the ocean is at the mercy of the environment, buffeted about by the universe. When it is cold in the ocean, bacteria are cold. The blood of the body buffers its cells (each of which, remember, is in essence a bacterium), making sure oxygen is constant and regulating, at least in birds and mammals, body temperature.
It is amazing that from a chimera of two kinds of microbes the complexity of our bodies evolved, but it is also a challenge. It is a challenge because every one of our cells needs oxygen. It is a challenge because anything that interrupts the cycling of blood interrupts everything. If blood stops cycling, oxygen stops reaching the cells. Because the brain requires the most oxygen—it has the most mitochondria—it is the first to feel the effects. It grows starved. The cells die. Da Vinci did not know the history of microbes or oxygen. He just understood that if the body was starved of blood, it would die. Blood is moved to each cell by the push of the heart until the heart stops, be it sweetly, as da Vinci would wish, or otherwise.
The mitochondria and their history and role were not really discovered until the 1970s. Their discovery meant that the human body was really multitudes held together by the glue between cells and by the heart and its circulatory system, a system whose real goal is to keep alive the great community of cells that each of us represents. This multitude includes our cells, the mitochondria inside them, our partner bacteria inside our guts, the bacteria on our skin, and much more. Death is always the result, in one way or another, when the circulatory system fails to provide oxygen, food, and messages to this diversity of cells. Death is the body’s falling apart, its failure to stay connected. We see this most obviously in hemorrhagic strokes. Hemorrhagic strokes are caused when blood vessels in the brain are blocked or rupture. A rupture occurs when a blood clot travels into the narrow vessels of the brain and causes a dam, on one side of which pressure builds up. The pressure leads the vessel to rupture. The rupture, in turn, causes blood to flow directly over the neurons of the brain. This, in and of itself, can cause some damage, but the real damage is that anything downstream of where the vessel ruptures fails to get oxygen and dies. Whatever is contained in those cells—whatever mix of memory and function—dies too. With a big stroke, whole parts of the brain are lost (and with a microstroke, just pieces). This, in the end, is what happened to da Vinci. It is also what happened to Harvey. I suppose one could fin
d some poetry in the fact that Harvey’s demise related to the failure of his circulation to reach every part of his body. But what one more obviously sees is the sadness we all face when the heart fails to reach every cell. While Harvey lived an extraordinary life of discovery, he died an ordinary death.
At the time of Harvey’s death, no one could do anything to treat problems of the circulatory system or problems related to the heart. Problems happened, and an individual died. Ultimately, there were many reasons for this. But the first one was that no one could detect a problem in the heart or elsewhere in the arteries or veins until it was too late. Strokes destroyed great minds. Heart attacks struck men and women dead where they stood, sat, ran, or danced. Only then did anyone know anything was wrong. Progress in dealing with the heart would have to wait for technology to catch up; it would have to wait for a way of seeing inside a living body and for someone wild enough to try.
5
Seeing the Thing That Eats the Heart
A man sees in the world what he carries in his heart.1
—JOHANN WOLFGANG VON GOETHE, FAUST
The tragedies of life are largely arterial.
—WILLIAM OSLER
One evening in 1929, Werner Forssmann sat at his favorite bar staring into the distance. From all appearances, he was more forearm than frontal lobe. He was a big man, a football lineman of a fellow. But he had an idea, and as the bubbles of alcohol removed his inhibitions, he decided to announce it. As his friends leaned in, he told them plainly: I am Werner Forssmann. I am twenty-five years old and I am going to insert a tube into the arm of a man and run it all the way to his heart. When I do it, I’m going to fix what is broken in him. “It will,” he roared, “change the future of the heart; I will change the future of the heart.”
He went on to explain what he would do. His friends were both enthralled and disconcerted. What they were hearing was unbelievable. Forssmann told his rapt and inebriated compatriots he had seen drawings in which veterinarians had run a catheter through the jugular of a horse, winding it all the way to its heart to detect the horse’s heartbeats.2 He found the drawings in an old textbook he had happened upon in one of his cupboards.3 When Forssmann saw the drawings of the horse experiment, he imagined a whole new science and medicine of the human heart in which the heart could be studied and treated while still beating without anyone having to open the patient’s chest. He clung to the sketch. Like a toddler with a favorite doll, he took it everywhere.
At the time Forssmann was contemplating this procedure, there were great barriers to its success. The heart was still viewed as both fragile and inviolable; it was the sacred and untouchable chalice of the body, much as it had been four hundred years prior in Italy. The horse heart could be studied, but it was enormous and sturdy (and, in any case, no one had dared to follow up on the earlier horse work). Not so the human heart. Also, Forssmann was a physician but not really a surgeon. He had obtained his medical degree just a year before. He applied to be a surgical resident at the Moabit Hospital in Berlin but had failed to get the position. He was then hired as a house officer in the Department of Gynecology at the much less prestigious Auguste-Viktoria Hospital in Eberswalde, Germany (his getting even that job appears to have taken a favor called in by his mother, who was friends with the chief surgeon). There, he slowly worked his way into the surgery department, more as an assistant than as a surgeon. At best, he would have been considered an unofficial resident. At worst, he was an assistant with a medical degree who was occasionally humored with a chance to use a knife. He did not have a lab or an office. He did not even have keys to the building. What he had, though, he had in spades: determination. He was ready to be the bull in the china shop of the heart. Horns down, he charged.
Werner Forssmann, while doing research as part of his doctoral dissertation in 1928, pauses to look out the window, cigar protruding proudly from his mouth. (Courtesy of The Werner Forssmann Family Archives)
Early in his career Forssmann spent many hours around corpses, part of being the low man on the totem pole. He performed rudimentary autopsies. He cleaned up the mess of dying. At first, the bodies disgusted him. It was a natural reaction. But with time, the disgust wore off, replaced by a tingling awe. So recently alive, the bodies were often intact in every way except for the beat of their hearts. In looking at dead bodies, Forssmann saw what others were beginning to highlight: that the hearts of many of the bodies were in bad shape. He could push his fingers into their valves. When he did, the valves felt hard. Often, the coronary arteries—those medusoid snakes on top of the heart—were nearly blocked by a hard white substance that had accumulated inside the walls of the vessels. Whether or not their hearts killed them, the bodies had been ready to go, each one sustained by only a narrow passage through which blood was forced to pass.4 Without knowing it, they had been walking tightropes with their eyes closed. At the time, and as would be the case for another thirty years, heart problems were viewed as fatal, a fall from the highest rope with no net. One could only watch. The heart stopped. The woman fell. The audience of doctors stood by and looked on. But it was worse than the tightrope. One could detect heart problems only in the dead. In the living, they were both invisible and untreatable. The fall from the tightrope went unnoticed until the body smacked the ground.
But Forssmann, as he pushed his fingers into the cadavers, began to think that some of the problems of the bodies were simply due to bad plumbing that might be fixed. The trouble was how to do the fix, how even to find what was wrong in the first place. Heart diseases were for the coroner to note rather than for the doctor to cure. Forssmann wanted to change that. The same procedure used on the horses might allow him to see some of what was going wrong in living humans, and, just maybe, mend it by releasing medicine into the heart or manipulating the heart muscle itself. How different could the hearts of horses and men be from each other?
Forssmann wanted to make progress, to push ahead. But he was also a conflicted man, a man caught repeatedly between dreams and bosses. As his daughter would later write of him, he was “a daring man who struggled with his passions, an adventurer who searched for pure reason, a tragic man who believed it was his duty to do what he thought was right to do regardless of the consequences.”
Forssmann imagined sending a device up through the arm vein of a patient, over the shoulder, and into the heart (the neck vein was also a possibility for entry, but Forssmann thought patients would object to the potential of scarring on their necks, where he would have to cut, vampire-like, into their veins). He would use the veins rather than the arteries because he could move the catheter in the direction of the blood; the catheter would pass with the blood through the valves that Vesalius had observed in the veins on its way to the heart. It would, he blindly hoped, pass without being stopped by the body’s ancient security doors.
Few thought that the proposal was worthwhile or safe. Across history, most radical thinkers confronted with a moment like this, when everyone doubted them, have backed off. Forssmann knew only to charge; it was belligerence more than bravery, a knuckleheaded leap. In 1929, after much arguing, Forssmann finally convinced his boss, Dr. Richard Schneider, of the value of his ideas. He showed him the drawing of the horse. His boss agreed to let Forssmann carry out the experiment, but only on animals—rabbits.5 In response to Forssmann’s pleas to try it first on a human, on himself, Schneider replied, “Drop this suicidal idea. What could I tell your mother if one day we should find you dead?”6 A scandal would ruin Forssmann’s family. Schneider was friends with Forssmann’s mother, and even if Forssmann did not worry about himself, Schneider was worried about her fate, as though Forssmann were a rambunctious teenager acting out.
Forssmann did not want to carry out the experiment on animals; he wanted to do it on human patients. He could have just waited, but he was not that kind of man, and so it was that he decided to do the first experiment on himself. He just wanted to see if he could successfully get a catheter to his heart, like the
veterinarians had done in the horse. The rest would follow. The idea was to insert the catheter and then take an x-ray to see how far the catheter had gone. As far as anyone knew, such a procedure stood a high chance of proving fatal. The heart was fragile, its caves delicate and easily disturbed—the glass palace at which one should not throw stones. Forssmann seems not to have cared much for his own safety, but he could not do the procedure entirely on his own. He had to enlist at least one other person, since Forssmann did not have access to the keys to the cabinets in which the catheters were stored.
At the time that Forssmann was working, very little innovation in the understanding of the heart and cardiovascular system had occurred since da Vinci or Harvey, all those hundreds of years prior, although there had been a little progress in medicine. Perhaps the greatest leap was that scientists now had the ability to see the heart and blood vessels in living bodies. The discovery of x-rays allowed the shape of the heart to be seen in living patients. In long exposures of x-rays on film, the heart showed up as a white body in outline behind the striped cage of the ribs. But that was not all. Dyes of different sorts, if allowed to course through the blood vessels, blocked x-rays. In doing so, and when the images were shown in positive instead of negative mode, they produced black shapes every place blood or other substances could course. The more blood, the darker the image. This method allowed beautiful and haunting images to be created of the brain and its main arteries, of the hands, and of the legs and their twisted rivers.7 But these methods work best in the dead, among whom diagnosis is often, well, a little late. They were too dangerous in the living.