Figure 3: Gas exchange at the alveolar level.

      We are attuned so closely to this process of inhalation and exhalation in our slumbering loved ones because we have an instinctive understanding of its urgency: while we can skip meals, breathing must be continuous. The system must be finely coordinated as gas levels need to be kept within a very narrow range in our blood. Receptors in our aorta and carotid artery continuously monitor levels of oxygen and carbon dioxide and send feedback to the respiratory center in our brainstem. Even the slightest change in the levels of gas will trigger more signals or fewer to go out to our muscles of inspiration. The activity in the respiratory center of our brainstem also feeds back to our cerebral cortex, or higher brain, making us aware of any impending danger. This creates the alarming sensation we are all familiar with if our brain senses something wrong with our oxygen or carbon dioxide levels, as when we hold our breath.

      Carbon dioxide is what causes most of the initial problems when we hold our breath, because as it builds up in our blood during a breath hold, it begins to break down into acid. This acid is toxic to our cells, especially as it begins binding with proteins and other molecules it shouldn’t, impeding the normal function of cells. As the breath hold continues, lack of oxygen also becomes a problem, and as cellular respiration in our mitochondria ceases with the dearth of oxygen, cellular death ensues. The cells of the heart muscles are especially sensitive to this, and cardiac arrhythmias can ensue in extreme cases of too much carbon dioxide or too little oxygen. Breathing is the most important thing we are aware of doing, and the body regulates it tightly.

The foundation of our understanding of these pulmonary processes, and indeed of all Western medicine, was laid in ancient Greece. After the mythical Apollo and his mystical son Asclepius, whose rod is the symbol of medicine today, the first legendary but real figure in the history of medicine was Hippocrates, born in 460 BCE on the Greek island of Kos. He is forever known for creating the oath that all physicians still recite when they receive their diploma, and is deservedly known as the Father of Medicine for his insight that disease was the consequence of natural processes and not the work of magic or the gods.27

In addition to contemplating many other anatomical systems, Hippocrates studied breathing. He recognized that the inhalation of air was fundamental to life. For this reason, Hippocrates and the Greeks viewed air as something vital and transcendent. They called it pneuma, which literally means air or breath but for the ancient Greeks also meant life force. This pneuma was inhaled and then passed through the lungs, into the blood, and on to the heart, where it became the pneuma zoticon, or vital spirit. This vital spirit was then carried to the organs, including the liver and brain, where it was transformed into pneuma psychicon, or animal spirit, which was considered the driving force, created by the body from air. From spirit (air or pneuma) to vital spirit to animal spirit, the Greeks and Hippocrates insightfully saw the essence of our existence as a continuum from the atmosphere.28

      Some five hundred years after Hippocrates, Claudius Galenus was the next great figure to change how we think about breathing and circulation. Better known simply as Galen, he was born in September 129 CE, in the Aegean Sea town of Pergamon, part of modern-day Turkey. His father, a wealthy patrician, originally had plans for his son to become a philosopher and statesman. These plans changed when the father dreamed that the mythical physician Asclepius visited him with a decree that his son study medicine. Galen’s father spared no expense, and Galen was educated at the best institutions throughout the Roman Empire.

      When he finished his studies, Galen settled into practice in Pergamon. He became the personal physician to the gladiators of the high priest of Asia by performing an act of daring. According to his own report, he eviscerated a monkey and then challenged the other physicians to repair the damage. When none stepped forward, he did the surgery himself, successfully restoring the monkey and winning over the high priest. He later moved to Rome and became the personal physician to several emperors, most notably Commodus, who reigned from 161 to 192 CE.

Galen contributed to many areas of medicine, and added to our understanding of the lungs and circulatory system. He noted that “blood passing through the lungs absorbed from the inhaled air the quality of heat, which it then carried into the left heart.”29 Human dissection was prohibited by Roman law, but Galen dissected both primates and pigs. He was the first to describe the two separate systems of circulation, the arteries and the veins. He believed that the liver, with its dark purplish interior, was where blood originated. From the liver, he postulated, half of the blood went out to the veins and was delivered to the tissues and consumed. The other half went to the lungs via a vein, where it picked up pneuma, then on to the heart, the arteries, and then the tissues.

      Although Galen’s theories on blood flow would be proven to be partially wrong, he was important, like Hippocrates, because of his methodology. Galen cemented the notion that medicine and disease were not the products of divine intervention from the gods but could be discerned from empirical evidence and deduction based on observation and cause and effect. Nonetheless, more than a thousand years passed before his ideas on the movement of oxygen within the blood’s circulation were corrected.

In somewhat ironic contrast to his philosophy, Galen’s ideas were accepted as gospel over the centuries, particularly his ideas on the flow of blood into both arteries and veins, and on the liver as the epicenter of blood production. Fortunately, the idea that the breath was important also did not change, as can be seen when the Renaissance scientist Alessandro Benedetti poetically wrote in 1497: “The lung changes the breath, as the liver changes the chyle, into food for the vital spirit.”30

The man who changed our understanding of blood flow was William Harvey, an English physician trained in Padua, Italy. He, like Galen, had a big personality, and he frequently walked around with a dagger on his belt, as was the fashion in rough-and-tumble Renaissance Italy. His opinion of his fellow man was not high, and a biographer who lived at the same time claimed, “He was wont to say that man was but a great mischievous baboon.”31

      Upon establishing himself in England after his Italian internship, Harvey published De Motu Cordis et Sanguinis (On the Motion of the Heart and Blood) in 1628, cementing his reputation as a giant in the history of medicine. This work was seminal in our understanding of the basic physiological principles of how blood travels in the body. Harvey had two breakthrough insights. He noted that he had learned from his Italian mentor that the veins all had one-way valves, pointed away from the tissues and organs and toward the heart. Why the venous system, which was postulated by Galen to bring blood to the organs as the arteries did, had back valves to keep blood away from those parts of the body was not easily explained.

      Harvey’s second important observation was made through painstaking dissections of humans and animals. He calculated that the output of the heart was a lot greater than previously thought, about five liters per minute. He correctly reasoned that the tissues could not consume that volume of blood each minute, as proposed by Galen. He needed a more reasonable explanation, a system that was simple yet elegant—and that went against fifteen hundred years of dogma. So he proposed something often found in nature: a system of reuse and recycle,