THE WISDOM OF THE BODY
The living being is stable. It must be so in order not to be destroyed, dissolved, or disintegrated by the colossal forces, often adverse, which surround it.
–CHARLES RICHET, NOBEL LAUREATE (1913)
The snapping of tree limbs jolted me out of a deep sleep. Peering through the front screen of our large tent, perched on a wooded bluff over the Tarangire River in northern Tanzania, I could not see anything outside in the pitch-black, moonless night. Maybe the wind had toppled a tree? I checked the clock — 4 a.m. — and rolled over, hoping to get a couple of more hours of rest.
Then I heard heavy footsteps, crunching at first in front of the tent, then on all sides of us, accompanied by occasional low rumbling, almost purring noises. They were really close. My wife Jamie was now awake.
A family of elephants had hiked up the slope from the riverbed to browse on the trees and shrubs on top. With no natural predators, the animals walked wherever they desired, and at 8,000 pounds or more with strong, forklift-like tusks, they simply bulldozed their way through any thicket. As we heard branches and trunks splinter, I wondered about the thin canvas that separated us. With utter disregard for the resting humans nearby and, thankfully, no interest in our rectangular refuges, they munched past dawn before heading back down the hill to drink.
As daylight came, we stepped carefully outside to photograph one straggler. Boy, elephants look even bigger when there is nothing between you and them. This bull was huge, more than ten feet tall at his shoulders, with giant ears. Stripping branches and leaves off of small trees, while ignoring the paparazzi peering around the corners of several tents, he seemed content. [Figure 1.1]
Until some noise from a tent spooked him. He trumpeted, pivoted to his left and took some quick steps in our direction.
There is more than one account of what happened next.
In my version, we dashed for the nearest tent, barreled inside, and instantly closed the zipper behind us (because four-ton elephants can't open zippers). We then just stood inside trembling and muttering, trying to regain our composure.
In the biological version of those few seconds, a remarkable number of things happened in my brain and body. Before my mind could even form the thought "Mad elephant! Run!" a primitive part of my brain, the amygdala, was signaling danger to my hypothalamus. This almond-sized command center just above the amygdala promptly sent out electrical and chemical signals to key organs. Through nerves, it signaled the adrenal glands that sit on top of my kidneys to release norepinephrine and epinephrine, also known as adrenaline. These hormones then circulated quickly through the bloodstream to many organs including: my heart, causing it to beat faster; my lungs, to open up airways and increase breathing rate; my skeletal muscles, to increase their contraction; my liver, to release stored sugar for a quick supply of energy; and smooth muscle cells throughout my body, causing blood vessels to constrict, skin hairs to stand on end, and blood to shunt away from the skin, intestine, and kidneys. The hypothalamus also sent a chemical signal, corticotropic releasing factor (CRF), to the nearby pituitary gland that triggered it to release a chemical called adrenocorticotropic hormone (ACTH) that traveled to another part of the adrenal gland and triggered the release of another chemical — cortisol, which increased blood pressure and blood flow to my muscles.
All these physiological changes are part of what is known as the "fight-or-flight" response. Coined and described a century ago by Harvard physiologist Walter Cannon, these responses are aroused by both fear and rage, and quickly prepare the body for conflict or escape. We opted for escape.
Cannon first became interested in the body's response to fear while conducting pioneering studies on digestion. X-rays had just been discovered when Cannon was a medical student; a professor suggested that he try to use the new gadget to watch the mechanics of the process. In December 1896, Cannon and a fellow student successfully obtained their first images — of a dog swallowing a pearl button. They soon experimented with other animals including a chicken, a goose, a frog, and cats.
One challenge to observing digestion was that soft tissues, such as the stomach and intestines, did not show up well on X-rays. Cannon found that feeding animals food mixed with bismuth salts made their digestive tracts visible, because the element was opaque to the rays. He also explored the use of barium; it was too expensive at the time for research work but was later adopted by radiologists (and still is used in gastroenterology today). In a classic series of studies, Cannon was able to observe for the first time in living, healthy, nonanesthetized animals, as well as in people, how peristaltic contractions move food through the esophagus, stomach, and intestines.
During the course of his experiments, Cannon noticed that when a cat became agitated, the contractions promptly stopped. He jotted in his notebook:
Noticed sev times very distinctly (so absol no doubt) that when cat passed from quiet breathing into a rage w struggling, the movements stopped entirely. ... After about ½ minute the movements started again.
Cannon repeated the experiment again and again. Every time, the movements resumed once the animal calmed down. The second-year medical student now had another finding to his credit. In what would become the second classic paper of his budding career he wrote, "It has long been common knowledge that violent emotions interfere with the digestive process, but that the gastric motor activities should manifest such extreme sensitiveness to nervous conditions is surprising."
Cannon's knack for experiments soon derailed his plans to become a practicing physician. His talent, rigor, and work ethic so impressed the distinguished faculty of the Department of Physiology at Harvard that he was offered an instructorship on graduation.
THE NERVOUS STOMACH
In his own laboratory, Cannon aimed to figure out how emotions affected digestion. He observed that emotional distress also ceased digestion in rabbits, dogs, and guinea pigs, and from the medical literature that also seemed to be true of humans. The connection between emotions and digestion suggested some direct role of the nervous system in controlling the digestive organs.
Cannon knew that all the outward signs of emotional stress — the pallor caused by the contraction of blood vessels, "cold" sweat, dry mouth, dilation of pupils, skin hair standing on end — occurred in structures that are supplied by smooth muscle and innervated by the so-called sympathetic nervous system. The sympathetic system comprises a series of neurons that originate from the thoracic-lumbar region of the spinal cord and travel out to clusters of nerve cells (called ganglia). From there, a second set of generally much longer neurons extend to and innervate target organs. Most of the body's organs and glands receive sympathetic input, including the skin, arteries, and arterioles, the iris of the eyes, the heart, and the digestive organs. These same organs also receive input from nerves originating in the cranial or sacral parts of the spinal cord. [Figure 1.2]
To figure out what stopped the activity of the stomach and intestines under emotional stress, Cannon and his students conducted a series of simple but fundamental studies. One approach was to sever the nerves leading to the digestive organs. Cannon found that when the vagus nerve (originating in the cranial system) was severed but the splanchnic nerve (part of the sympathetic system) was left intact, the inhibition of peristalsis could still be induced by fear. In contrast, when the splanchnic nerves were cut and vagus remained intact, there was no response to fear. These results showed that the inhibition of peristalsis induced by emotion required the sympathetic splanchnic nerves.
Cannon had noticed that the inhibition of gastric activity often long outlasted the presence of whatever provoked the response. This suggested to him that there might be a second mechanism beyond direct nervous impulses that might prolong the agitated state. It had been reported that adrenalin, a substance extracted from the central portion of the adrenal glands, when injected into the bloodstream could produce some of the effects produced by stimulation of the sympathetic nervous system. Cannon wondered whether the adrenal glands might be involved in the body's response to fear and anger.
To test this possibility, Cannon "made use of the natural enmity" between dogs and cats. He and a young physician, Daniel de la Paz, compared blood samples of cats taken before and after they had been exposed to the stress of barking dogs. They discovered that the blood of frightened cats contained a substance that when applied to a small strip of isolated intestinal muscle stopped it from contracting. This was the same effect observed when adrenalin was applied to the muscle strip.
Epinephrine was one of the components of "adrenalin" produced by the adrenal glands. Cannon and his colleagues also found that epinephrine sped up heart rate, the release of sugar from the liver, and even blood clotting. These same effects were triggered by pain, as well as by fear or anger. None of these effects occurred when the adrenal glands were removed, or when the nerves leading to the adrenal glands were cut. Thus, the sympathetic nervous system and adrenal glands worked in concert to modulate other body organs in stressful conditions.
Cannon suggested that the responses induced by epinephrine reflected the "emergency" function of the adrenal glands in preparation for fight or flight, or in response to pain. A firm adherent to Darwin's principle of natural selection, Cannon interpreted the roles of the adrenal system through that lens:
The organism which ... can best muster its energies, can best call forth sugar to supply the laboring muscles, can best lessen fatigue, and best send blood to the parts essential in the run or fight of its life, is most likely to survive.
Cannon's student Philip Bard subsequently demonstrated that the hypothalamus is the critical part of the brain for control of the so-called involuntary (autonomic) functions of the nervous system, including digestion, heart rate, respiration, and the fight-or-flight response. Both this part of the brain and these emergency responses are ancient. This same set of responses helped our ancestors avoid lions and hyenas on the savannah, just as they help pedestrians to dodge taxis in New York today, or tourists to run from elephants.
Cannon was an Ivy League but not an Ivory Tower scientist. In 1916, three years into World War I, as the battlefield in Europe turned into a horrific stalemate that produced enormous casualties, it seemed increasingly likely that the United States might be drawn into the conflict. Cannon was asked to chair a special committee of physiologists to advise the government on ways to protect the lives of soldiers and civilians. He learned that one of the most serious problems in battlefield medicine was the development of shock in wounded soldiers. Cannon recognized some of the shock symptoms — rapid pulse, dilated pupils, heavy sweating — from those he had observed in his experimental studies of animals under stress. Wounded soldiers who exhibited these symptoms often went downhill quickly and died. "Are there not untried ways of treating it?" he asked a fellow physiologist.
Cannon was so taken with the problem of shock that he began some animal experiments to see whether he could figure out ways to mitigate the syndrome. When the United States did finally enter World War I in April 1917, Cannon was forty-five years old and the father of five, and could have easily been excused from service. Instead, he volunteered as a member of a Harvard Hospital Unit that was one of the first American medical teams to go to Europe. Cannon requested to serve in a shock ward near the front lines in northern France.
Cannon said goodbye to his family in Boston, took a train to New York, and boarded the troopship Saxonia bound for England. The voyage overseas would take eleven days. To avoid detection by German submarines, the ship was blacked out at night, with all of its portholes closed. While ships usually have lights at both ends so as to avoid collisions, the Saxonia lit only its stern, to help draw any torpedo off target. Eight days into the voyage, as the ship drew nearer to the English coast, the orders came to sleep in one's clothes; if hit, it was better to jump into the lifeboats fully dressed. As the ship hit choppy seas in rain and fog, Cannon was relieved, "not a favorable condition, I should say, for good hunting," he wrote to his wife Cornelia. The appearance of a British destroyer escort further eased anxieties.
After arriving safely in England, Cannon continued on to the first of several field hospitals. A wave of casualties soon arrived from a major British offensive. Although Cannon had not practiced any medicine since his graduation from medical school seventeen years earlier, he asked to assist in the operating room, dressed wounds, and worked in the wards.
Cannon then moved to a hospital nearer to the front. He watched helplessly the heartbreaking, rapid decline of scores of soldiers. Why the soldiers died was a mystery that Cannon and several other American and British physiologists were hell-bent to solve.
One important clue to shock came from the then-novel approach of measuring soldiers' blood pressures, not just their pulses. Healthy soldiers had pressures of about 120–140 (mmHg; the abbreviation stands for millimeters of mercury), while shock patients had pressures below 90. It was learned that if this fell to 50–60, the patient did not recover.
A low blood pressure meant that vital organs would have difficulty obtaining sufficient fuel and disposing of waste. Early in his time in France, Cannon decided to measure the concentration of bicarbonate ions in the bloodstream of shock patients, a critical component of the blood's buffering system. He discovered that the patients had lower levels of bicarbonate, which meant that the normally slightly alkaline blood had become more acidic. And he found that the more acidic the blood was, the lower the blood pressure and the more severe the shock were. Cannon proposed a simple possible therapy: administer sodium bicarbonate to shock victims.
Cannon reported the first results in a letter to his wife Cornelia in late July 1917, just two months after his arrival in Europe:
Well, on Monday there was a patient with a blood pressure of 64 (the normal is about 120) millimetres of mercury and in a bad state. We gave him soda [sodium bicarbonate], a teaspoonful every two hours and the next morning the pressure was 130. And on Wednesday a fellow came in with his whole upper arm in a pulp ... such cases usually die. At the end of the operation he had the incredibly low pressure of 50; soda was started at once and the next morning the pressure was 112.
Cannon described three other soldiers who had been treated that same week and also had been "snatched from death," including one who was given the sodium bicarbonate intravenously and whose rapid respiration and pulse eased quickly.
Cannon and the Allied medical command were thrilled by this innovation. Since shock was often brought on by surgery, the use of bicarbonate was adopted as a standard preventative measure in all critical cases. Cannon and his colleagues also advocated other procedures for warding off the development of shock, including protecting wounded soldiers from exposure by wrapping them in warm blankets, giving warm fluids, transporting on dry stretchers, and using lighter forms of anesthesia during surgery.
To promote these methods, Cannon organized the training and deployment of "shock teams" to treat shocked soldiers on or near the battlefield. To see how the teams performed in battle, he went on an inspection tour close to the front.
In mid-July 1918, he was visiting a hospital near Chalons-sur-Marne, in eastern France. After spending an evening socializing with other doctors, Cannon retired to bed. He could hear guns firing in the distance, but that was typical. Just before midnight, Cannon was jolted awake by "the most stupendous, the most terrific, the most inconceivably awful roar ... like thousands of huge motor trucks rushing over cobblestones." He jumped to his window and saw entire horizon lit up with gunflashes and shellbursts. He heard the zip-sish sound of a shell passing nearby, which exploded near the hospital. Shells continue to hit within a mile of the building, one about every three minutes for four straight hours.