Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (27 page)

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An Unexpected Phenomenon

It's Electric!

As in the great age of exploration, when the coastal contours of a continent were first outlined and thereafter its rivers, mountains, and valleys penetrated, so was the terra incognita of the heart and the circulatory system explored. Long considered a “sacred organ,” the heart was conventionally viewed as the body's spiritual center. Simply to consider the emotions attributed to the organ reveals its profound importance in man's mind: heartache, heartbroken, heartfelt, heartless, heartsick, heartwarming. Researchers were traditionally fearful of the potential dire consequences of undertaking investigations directed to unveil the heart's mysteries.

The first to ponder them was Galen, the second-century Greek physician. Forbidden to dissect human cadavers by Church authorities, he could only guess at how the blood and the heart work in tandem. He theorized that the blood passes through invisible pores in the heart's septum (the tissue that divides the heart's ventricles), with the heart acting as a massive pump. Central to his beliefs was that the heart impressed the blood with vital spirits. It was not until 1628 that William Harvey in England discovered that the heart repeatedly pumps the blood through a closed system of arteries and veins. Because blood coursed in a circle in the body, it was referred to as circulation or the
circulatory system. But for hundreds of years thereafter, that was all doctors knew. Even three centuries after Harvey's discovery, most doctors could not accurately diagnose a heart condition.

In 1856 two German scientists, Albert von Kölliker and Heinrich Müller, accidentally discovered electrical activity in cardiac muscle.
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Working with frog preparations, they had excised a leg nerve with its attached muscle and had just opened the chest wall of a second frog when they were called out of the laboratory. Upon returning, they encountered an astonishing and wholly unexpected phenomenon. The muscle of the excised preparation from the first frog was contracting along with the heartbeat of the second frog. The cause was evident: they had inadvertently dropped the first frog's excised nerve end on the exposed surface of the heart of the second frog. They accidentally discovered that the heart produces an electrical current with each beat.
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It was Augustus D. Waller, a British physiologist working at London's University College and at St. Mary's Hospital Medical School, who first recorded the heart's electrical deflections. Waller was an unconventional and somewhat flamboyant figure, “endowed with out-spoken friends and enemies.” In contrast to other physicians of the time, who always dressed somberly in morning coats and silk hats, he sported a double-breasted blue jacket and a gray beard that made him look exactly like a skipper in the merchant navy. Photographs show him habitually smoking a cigar and invariably accompanied by his bulldog, Jimmy, who not only was his constant companion but also served in Waller's initial animal experiments.

Waller showed that the currents of the heart could be studied without opening the thorax (the upper part of the torso) simply by putting electrodes, to which a capillary electrometer was attached, on the animal's body. In 1887 he was able to record a human heart: “I dipped my right hand and left foot into a couple of basins of salt solution which were connected with the two poles of the electrometer and at once had the pleasure of seeing the mercury column pulsate with the pulsation of the heart.”
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The instrument Waller used, the Lippman capillary electrometer devised fifteen years earlier in Berlin, consisted of a column of mercury within a very thin glass tube (capillary), one end of which was
immersed in a solution of dilute sulfuric acid. The electrical discharges from the heart caused a fluctuation of the mercury level due to the change in surface tension, and its changing level was recorded on sensitized paper. Inexplicably, however, Waller never recognized the enormous potential of his observations for clinical use. Several years later he would admit, with more than a touch of remorse, “I certainly had no idea that the electrical signals of the heart's actions could ever be utilized for clinical investigation.”
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“T
HE
S
ECRETS OF THE
H
EART
”

This lost opportunity was seized by Willem Einthoven, a recent medical school graduate of the University of Utrecht in the Netherlands. Einthoven (pronounced Aynt-ho-fen) was born in 1860 in Java, one of the major Indonesian islands, then part of the Dutch East Indies. The name was Dutch, but the family traced its ancestry to Jews who had migrated to the Netherlands from Spain during the Inquisition. After the death of his father, a military physician, Willem's mother brought the family back to Utrecht.

Appointed chairman of the physiology department at the University of Leiden in 1886 at the age of twenty-six, Einthoven noted the disadvantages of the recording system that made measurements erratic and inaccurate: the friction and inertia of the mercury column, its insensitivity, and the arduous task of making long and detailed mathematical analysis and reconstruction into a curve that he called an electrocardiogram. Most notably, the unit was extremely sensitive to vibration. Large horse-drawn carts clattering over the cobblestones in the street outside his laboratory would shake the wood-framed building and jostle the mercury level in the capillary electrometer, resulting in multiple inaccuracies.

Einthoven removed floorboards and had a hole dug ten to fifteen feet deep and filled with large rocks in an attempt to build a stable base for the unit. These efforts, however, were to no avail. He would have to invent his own reliable instrument that could accurately record the tiny electrical charges that accompany each heartbeat. His challenge was to pick up the faintest electrical signals from the body
and use them to produce a permanent recording of the beating heart. After six years of work, he successfully developed the string galvanometer, a delicate thread conducting the heart's minuscule electrical current through a magnetic field.
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In our electronic age, we can only look back with admiration at the investigation of bioelectricity with self-assembled crude equipment.

Critical to its success was the development of an extremely thin string sensitive enough to detect the subtle changes in the magnetic field brought about by a heartbeat—and these changes had to be recorded accurately. Einthoven devised the right string in an ingenious way, using a bow and arrow and some quartz. First he attached a piece of quartz to the tail end of an arrow. He heated the quartz, and, as it melted, he shot the arrow across the room, creating a fine string of quartz.
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A mere 0.0001 inches wide, the microscopically thin wire could not be seen with the naked eye. Einthoven solved this problem with yet another clever design. When he illuminated the quartz string against a light background, the difference in light intensity occasioned by its faint shadow could be perceived by the eye. Coated with nebulized silver for purposes of conduction, the string was suspended between the two poles of a large electromagnet. Oscillations of the wire, responding to cardiac electrical deflections, were recorded by an optical system that focused the shadow of the string on a uniformly moving photographic glass plate. Time lines were projected onto the photographic plate by means of large spokes of a bicycle wheel that rotated and interrupted the beam of light at regular time intervals. Linear deflections of the string were then converted to voltage.

Einthoven's galvanometer was a huge construction. Its complexity may have looked like a Rube Goldberg cartoon as invented by his wacky character Professor Lucifer Gorgonzola Butts. It weighed about 600 pounds, occupied two rooms, and required five people to operate it. Nevertheless, its most delicate part, the string galvanometer, was the most sensitive electrical measuring instrument yet devised.
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A subject would immerse his hands or feet in large bowls or buckets of saline used as electrodes. This forerunner of the minuscule portable
ECG instruments of today yielded three waveforms, called P, QRS, and T. The first human electrocardiogram was recorded by the instrument on November 18, 1902. The quality of the records was superb, and it became the standard method until the 1950s, when direct-writing instruments became available.

The Bow and Arrow behind Glass

The seminal importance of Einthoven's quartz string is memorialized in the Boerhaave Museum in Leiden, the Netherlands’ National Museum of the History of Science and Medicine. Wandering through it, passing microscopes and globes, surgical instruments and pistons, one is struck by a four-foot-high glass exhibit displaying Einthoven's original bow and arrow, whose inscription emphasizes that “the recording of the first electrocardiogram was a typical do-it-yourself job.”

To demonstrate the clinical usefulness of his electrocardiogram, Einthoven arranged for it to be linked to the university hospital one mile away by underground telephone lines to transmit the signals from the bedside so that he could undertake a systematic study of cardiac abnormalities.
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Professional jealousy, however, abrogated the arrangement between Einthoven and the hospital after a few years. The physician in charge of the hospital's department of medicine was embarrassed by Einthoven's ability to diagnose a heart irregularity before doctors could discern it at bedside and felt further that Einthoven was unfairly getting all the credit for this innovative technique.

Eventually Einthoven was able to put together a deal with the Cambridge Scientific Instrument Company of England, headed by Horace Darwin, the youngest son of Charles Darwin. Einthoven's model was redesigned by the company and reduced considerably in size to a table model in 1911. An early prototype was loaned to London physican Thomas Lewis in 1909 and installed under a staircase in the basement of the University College Hospital in London.
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(In 1913, at the age of only thirty-two, Lewis published the first definitive
textbook on clinical electrocardiography.) By 1925, a total of 450 of these machines had been installed in the United States.

Knowledge of coronary artery disease and myocardial injury had evolved very slowly. The chest pain that occurs when the heart muscle is deprived of oxygen is called angina pectoris, or simply angina. This is brought about by occlusion or spasm of a coronary artery. If the heart muscle actually dies — “infarcts” — the condition is sometimes fatal. Once known in medical terminology as coronary thrombosis, such “heart attacks” are now simply referred to as “MIs,” short for myocardial infarctions.

The classic signs and symptoms of angina were described as early as 1772 by the English physician William Heberden, who stressed the temporary “sense of strangling and anxiety with a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or continue.” Nitroglycerin for its relief was initiated more than one hundred years later.
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It was not until 1912, however, that someone made the first bedside diagnosis of a heart attack. James Herrick, a Chicago internist, was called to the bedside of a banker in severe distress with extreme chest pain, cold skin, nausea, and a racing pulse. After consulting with other physicians, he was not even sure what organ was causing the problem. He and his colleagues pondered many possibilities, including acute pancreatitis and pneumothorax (punctured lung). Herrick finally guessed that there was a clot in the coronary artery. The patient subsequently died, and, much to the pathologist's surprise, Herrick was proved correct at autopsy. Herrick reported the case in the
Journal of the American Medical Association.
His paper “Certain Clinical Features of Sudden Obstruction of the Coronary Arteries” was a giant step in the medical understanding of heart disease, but it stirred little interest. Writing a quarter of a century later, Herrick explained:

The fate of the early paper was a surprise to me and a keen disappointment. I did not realize, as I do now, that in medical history, as in the history of the growth of ideas in general, while some new facts are accepted as soon as announced, or at least attract enough attention to be subjects for discussion, very often others are passed unnoticed or unapproved until again brought forward in a more striking form or with more convincing proof and at a time when the medical world is more ready to listen.
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Doctors began diagnosing heart attacks at their patients’ bedside, but they couldn't always be sure that the symptoms they saw were not due to causes other than myocardial infarction. It was several more years before cardiologists began using Einthoven's ECG to more specifically diagnose heart attacks.

Even as late as 1924, Einthoven himself was not fully aware of the diagnostic importance of his instrument. Samuel Levine, a Harvard cardiologist, related an incident that occurred during a visit from Einthoven:

He [Einthoven] and I were seated in the electrocardiographic room chatting about one thing or another, when Miss Bertha Barker, our devoted and efficient technician, brought in a wet electrocardiographic tracing that she had just taken and developed. She interrupted our conversation and asked me whether she should telephone the medical house officer on the wards and tell him that the patient had an acute coronary thrombosis. The understanding in the laboratory was that if a tracing were taken and showed certain changes with which Miss Barker was quite familiar, she was to telephone the intern directly and not wait until the following morning at 9 o'clock, when I usually read all the tracings of the previous day. When I looked at the electrocardiogram she had just taken, I confirmed her diagnosis of acute coronary thrombosis and she left. On overhearing this conversation, Professor Einthoven was amazed. He remarked, “Do I understand correctly that this lady who is not a physician can make a diagnosis of acute coronary thrombosis from the electrocardiogram, without seeing the patient?”
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