The Man Who Touched His Own Heart

by Rob Dunn

  The task at hand, mad or not, was difficult. Helen Taussig, who spent her entire career studying and helping children, had to figure out, essentially on her own, how to pull the feathers off birds and dissect their tiny hearts. What was more, she was going to need to study a lot of birds. If one wants to study the evolution of, say, a beak, one needs to measure just a few beaks to know what they tend to be like in a particular species. But Taussig was not interested in the average condition; she was interested in those anomalous ones, and so she had to study many, many individual animals to measure each of those anomalous conditions even once. To discover deformities, she dissected the bodies and hearts of hundreds and then thousands of birds. She told colleagues to look for dead birds. She scoured the streets herself. She made friends with someone who traveled to radio and television towers where birds often died due to collisions.

  Most of the birds she ended up with were tiny. Her hands, long used to the small bodies of children, had to grow accustomed to the even smaller forms of sparrows and starlings. While her friends enjoyed their retirements, she performed the most difficult dissections of her life. She drew what she saw. She saved interesting hearts. She took notes; she pondered. She tried, after a career among hearts, to make sense of it all. She could have gone on forever, dissecting more animals and records to see the diversity of ways that hearts can go wrong, but she felt age creeping up on her and leaping at her mind. She drafted a paper based on what she saw. Things were going well, but just to be on the safe side, she provided instructions to her friends of what they should do with her late-life work should anything happen to her.

  By the time she drafted her bird article, Taussig had already produced the most comprehensive paper written at that time (and to date) on the congenital deformities of mammals. In her focal mammal, humans, she found that the same congenital deformities were common all around the world, independent of where or how people lived. This, on its own, suggested to her that the deformities were not strongly associated with the environment, with mutagens, for example. When she looked at those nonhuman mammals that had been studied well, they too showed the same congenital deformities. Dogs and sheep, for example, suffer the same congenital deformities as humans in the same relative frequencies. The question now was whether the same would be true of birds.

  Taussig predicted that those congenital deformities that related to shared, ancient features of the heart should be the same in birds and mammals but that those deformities related to the new features of the heart, features that had evolved since the separation of birds and mammals, should be different. In both cases, she was right. In the paper she had been working on, Taussig showed that some kinds of heart deformities, particularly those that caused cyanotic (blue-baby) diseases, were common among many mammals but also among birds. These defects, shared across the mammals and birds, seemed to Taussig to reflect problems in development at least three hundred million years old (the time at which the lineage of birds and humans split). Other problems seemed unique to the birds; she never saw a bird with two hearts, but two-hearted birds seemed to have been convincingly documented by others. Then there were ventricular-septal defects in birds, in which there was a hole between the two ventricles. Superficially, these defects looked like those in mammals, but their details were consistently different.

  Taussig took these observations and came up with a big new set of ideas about congenital heart diseases. She had explanations not only for the origins of congenital heart disease but also for the origins of the complexities of the heart in the first place. Then, on May 21, 1986, while driving her friend to a polling station near her home in Kennett Square, Pennsylvania, Taussig’s car was hit by another car she failed to see coming. She died later the same day at the hospital, three days before her eighty-eighth birthday.1 Taussig’s friends honored her wishes and published her paper, despite their skepticism, two years later, in 1988, though they would preface it with caveat after caveat in doing so, even including in the introduction to the paper the line “[Taussig] had no intent to label this work a scientifically based research project.” Five thousand birds is an awful lot of birds to dissect for someone who doesn’t think she is doing science-based research. Ultimately, her friends were too quick to apologize, and they were wrong to have doubts. Taussig’s paper was brilliant, science at its most creative. But no one ever discovered Taussig’s paper. It is referenced just once by another scientist (writing in Polish), except where it is mentioned in biographies of Taussig as an example of how she kept busy in her old age.

  Fortunately, during the past ten years, the ideas that so captivated Taussig have begun to be explored independently by evolutionary biologists. Evolutionary biologists have spent the past hundred years or so trying to reconstruct the big evolutionary story of the heart, how it evolved, and how it functions under normal conditions. Now they have begun to consider, in light of this big evolutionary story, human heart problems. As they have, what they’ve found suggests that Taussig was onto something. Considering the evolution of the heart alters how we think about congenital heart disease but also how we think about that even more common plague, coronary artery disease.

  The story of the evolution of the heart is embedded in every heart and how it works or fails to work. The heart and its problems, as evolutionary biologists tell it, begin not with birds and mammals but instead at some point prior to 550 million years ago, when the first multicellular creatures appear in our fossil records of the sea. Nutrients and gases could diffuse into single-celled creatures, but as organisms grew larger, some cells were inevitably on the inside of the creatures of which they were part. Those inside cells required plumbing2 so that nutrients and gases could get to them. The first blood vessels emerged before the first heart.

  Sponges (which are animals, though just barely) have the simplest circulation systems of any living organism. A sponge does not move. But it is filled with pipes through which the sea can be moved. Thin hairs in those pipes urge seawater along. The sea itself is part of the sponge’s heart. As the water moves, the cells lining the sponge’s network of pipes and tubes extract nutrients and oxygen from the sea and release waste.3 The sponge’s system may seem crude, but it works sufficiently well that sponges continue to thrive. It is interesting for that reason alone, but also because evolutionary biologists suspect that the sponge’s humble pipes are very similar to our own cardiovascular system’s antecedent. Some of the human genes associated with veins and arteries are the same genes involved in producing the simple tubes of the sponge.

  From this beginning, the descendants of the first sponge eventually evolved bodies big enough to require a pumping heart. In tens of millions of years—which to paleontologists is a very short stretch of time—many new and larger lineages evolved. In the few sites where good fossils of early multicellular creatures have been found, such as the Burgess Shale (in today’s British Columbia), paleontologists have found a circus of strange multicellular life, a record of evolution as it explored different body plans. These early animals were more diverse in nearly every external feature than are modern animals, and one presumes the same was also true of their internal features. They may have tested out a variety of types of hearts. Many of the Burgess Shale species would disappear, extinct before they really got started, but several persisted, one generation to the next, until today, and in each one of those persistent forms—the ancestors of mollusks, worms, insects, and vertebrates—there is a primitive heart. Today, the genes for hearts in the descendants of these lineages are similar, suggesting they all derive from one ancient invention of the heart in the time of the Burgess Shale or slightly before. Your heart and the heart of a worm had the same beginnings.

  In most lineages of animals, the heart stayed simple, nothing more than a squeeze box of spongy muscle, even in the earliest members of the vertebrates, the subphylum that includes humans. The first vertebrates were fishlike but not yet what we would recognize today as fish. In these animals, the heart’s primary role
appears to have been to move nutrients around the body. Nutrients were gathered by netlike gill structures and sent through the blood. The heart squeezed blood in both directions, fore and aft. When it did, Colleen Farmer, a biologist at the University of Utah argues, it also squeezed oxygen-enriched blood from the skin into the nooks and crannies among the heart’s spongy cells. (As the heart expanded after contraction, the oxygenated blood would have entered from the skinward side.) The very first role of the heart included supplying blood to itself.

  With time, fish evolved to feed primarily with biting mouths, and when they did, the role of the gills became exclusively that of sifting oxygen from the sea and releasing carbon dioxide. Simultaneously, the skin ceased to be an important organ for obtaining oxygen. With the advent of a biting mouth, the heart of the fish became more complex. It evolved a two-chamber structure very much like what a human heart would look like if it had just a single atrium and a single ventricle. The atrium allowed more blood to collect so that when it was pumped, the pressure generated was higher. The blood then pumped around the body in one cycle: Heart-gills-body. Heart-gills-body. This means the blood returning to the early fish’s heart was always low in oxygen because the other tissues of the body got to the oxygen first. The same is true in most modern fish. As a result, fish are subject to sudden death after vigorous swims, sudden death akin to a human heart attack in that it is due to a lack of oxygen to the heart.

  Aside from making fish susceptible to sudden death from exertion (which they mostly appear to avoid through knowing their own limits), the fish heart is strikingly elegant. The human heart, like all mammal hearts, has two separate circuits—the left pumping blood out to the body, the right pumping it to the lungs for oxygen—while the fish heart gets the job done with one. In fact, fish hearts more than get the job done. By any real measure, fish have been more successful than mammals. There are many times more fish species than mammals species. That their system works begs the question of why our system became so much more complicated. The explanation for our complexity lurks just beneath the waves.

  Lungfish are strange. They have gills, like other fish, but also, as is perhaps obvious from their name, lungs. To use their lungs, they reach up to the surface of the water and gulp air with their funny lips. They seem like primitive vestiges of something, an evolutionary bobble that has survived. But they are also a clue to understanding our hearts and their fallible complexity.

  Lungfish were first discovered in 1837. A specimen was packed in clay and shipped to the British anatomist Richard Owen for study. Owen was well prepared to consider a new kind of fish. He had examined the bodies and bones of more species of fish than nearly anyone in history. He had an eye for subtle differences, a kind of visual intuition honed by thousands of hours of practice. But this damned fish confounded him. On the outside, it was clearly a fish, but as he peered inside its body, it seemed as if, in some fairy realm, the insides had been switched out and replaced with those of a snake or a frog.

  Beginning with Owen, lungfish came to be viewed as interesting but rare anomalies. Yet, eventually, scientists realized there had been hundreds, perhaps thousands, of lungfish species. They were once a dominant life-form. As we now understand it, the story goes something like this: First, fish had gills to gather food. A subset of those fish evolved lungs in addition to their gills, primarily to gather oxygen, and then those fish, the lungfish, became rare. In light of this, the new questions become why and how lungfish became so successful and then why they became rare. Answering these questions would be of purely academic interest, except that the fish from which all terrestrial vertebrates, and their hearts, descended was a lungfish.

  About 360 million years ago the first lungfish climbed onto land. Of course, there were many challenges to being on land. The lungfish had to evolve feet from its fins and deal with extra gravity, but the lungs made land and humankind possible; they allowed our first terrestrial ancestors to get enough oxygen to their hearts. Although Darwin suggested lungfish evolved lungs from swim bladders (organs used by fish to stay buoyant), the opposite is true: swim bladders evolved from lungs. Lungs allowed fish to get more oxygen to their hearts in order to be more active in fleeing and chasing. The lungs were a benefit to the activity of the heart in the sea (just why lungfish became rare in the sea after conquering the land is not clear),4 and they offered the same sort of benefit on land. That we have lungs to which our hearts pump blood is a quirk of our ancestors’ attempts to be predators or avoid becoming prey.

  Once these vertebrates were on land, an arms race began, an arms race that led to the major lineages of terrestrial vertebrates and was made possible through the evolution of the heart. Any descendant of the original lungfish that was more mobile than others could capture hard-to-catch prey or flee hard-to-escape predators. As a result, some lineages began to evolve hearts that were better at distributing oxygen, allowing more activity. It was a kind of evolutionary treadmill. Being more active—whether to catch or to flee from another animal—required more oxygen, which required a bigger and better heart, which in turn required more oxygen and food.

  Richard Owen’s drawing of the lungfish Lepidosiren annectans (now called Protopterus annectans), a species that is similar in many features, including both its lungs and its feetlike fins, to the ancestral lungfish from which all land vertebrates ultimately evolved. (Courtesy of the Proceedings of the Zoological Society of London)

  The first new (and still extant) vertebrate lineage to evolve on land from lungfish was that of the amphibians. In amphibians, the two-chambered heart is sufficient as long as they move slowly and don’t stray far from the water (where they can gather additional oxygen directly through their skin). The circulatory systems of amphibians are like those of lungfish. But this keeps amphibians bound to the water, tethered by their lunglike skin.5

  The lineage of lizards, snakes, and turtles evolved a bigger, more efficient heart with two atria (like the human heart) and a partially divided ventricle. This new heart looked much more like a modern human heart than any that had come before, especially as it now had two circuits, one that ran blood from one side of the ventricle to the lungs and another that ran blood from the other side of the ventricle to the body. This heart allowed lizards and snakes to colonize the great first continent all the way to its inner reaches. This heart introduced a new problem, though: the blood coming back from the body through the right atrium was devoid of oxygen. Lizards, snakes, and turtles dealt (and deal) with this by having a hole between the nascent chambers of the ventricles so that oxygen-rich blood from the right side sloshes to the left. This sloshing works to nourish the heart muscle but is inefficient.6

  Then, very recently, roughly around 180 million years ago for mammals and a little earlier for birds, warm-bloodedness evolved. Warm-bloodedness offers multiple advantages. It allows animals to be active all the time, even when it is relatively cold. Warm-bloodedness also helps to prevent colonization by many pathogens. The fungi that plague reptiles and amphibians, for example, mostly leave mammals and birds alone. Our bodies are too hot for mushrooms to grow in them. But these advantages come at a cost. Warm-bloodedness requires a constant supply of oxygen to cells all around the body so that they can metabolize and, in doing so, produce heat. As a result, warm-bloodedness requires the heart to be much more efficient (it also has to pump more frequently). Evolution dealt with this cost through the origin of a fully segmented ventricle. Blood no longer sloshed back and forth from side to side. There was no time for such inefficiency.7 These ventricles evolved a full division with no room for leaks (creating a new problem in terms of oxygen supply to which we will soon turn). Birds and mammals both evolved this four-chamber system, independently. What was good for the archaeosaur (the first flying reptile) was also good for the first rat-size mammal running beneath the feet of dinosaurs.

  All of this evolutionary context (with a few updates to reflect our modern understanding) that Taussig had begun to grasp led her to thin
k that, in light of evolution, congenital heart diseases might make sense. Taussig noted that those rare congenital disorders of the valves or the left atrium or ventricle, all of which are as ancient as fish, seem to be found in essentially all vertebrates. The rarer deformities of the atria are found, typically, in those land animals that have added a second atrium. But the most common deformities all seem to relate to the right ventricle and those parts of the heart that formed with it. The right ventricle is the new one. The left ventricle corresponds to the original ventricle of the fish, amphibian, or lizard. The right evolved in mammals and birds. Taussig did not fully understand what this meant in terms of these congenital problems, but it seemed important. The major deformities arose with the origin of a second ventricle, but why? We now know.

  During development, the heart, to a greater extent than any organ, recapitulates many of the changes it went through during evolution.8 It starts as a tube. It goes through some loops and hoops, and then, for a time, resembles the heart of a fish, with one ventricle and one atrium, and then that of a lizard, with a single, large ventricle. If everything goes right, that big ventricle then divides partially during fetal life and closes fully just before birth. Recent research has revealed that the activity of a single gene, Tbx5, governs many aspects of the late stages of heart development in mammals and birds. In snakes, turtles, lizards, and amphibians, this gene and the genes it controls are expressed—the first step in going from the code of the gene to the physical product of the protein—across the entirety of the ventricle during development. Not in mammals and birds. In these animals, it is expressed in the left ventricle and then stops, abruptly. This pattern in expression tells other genes where to act. The placement of the abrupt stop determines where the wall between the ventricles is located. The evolution of the extra ventricle of both mammalian and bird hearts appears to have happened through changes in how this single gene is expressed. As Taussig anticipated, adding a new chamber was not so complicated after all. It mostly required a change in the heart’s template. But this simplicity came with trade-offs.