Muscle and Blood

How does the body work?

This question about the general nature of the life process is as old as human thought. Both philosophers and physicians have speculated and written about the mechanism of life and the special functions of body organs. Ancient man believed that the heart was the home of the soul. Fortunetellers used the livers of animals to try to predict the future. From these crude beginnings arose the science of physiology.

Physiology appeared a gruesome and reprehensible busi­ness-‑certainly not a gentleman's pursuit. A first‑century Roman scholar, Celsus, wrote a horrifying description of the activities of Alexandrian scientists: "They laid open men whilst alive, criminals received out of prison from the kings, and whilst these were still breathing, observed parts which beforehand nature had concealed, their position, colour, shape, size, arrangement, hardness, softness, smoothness, relation, processes, and depressions of each, and whether any part is inserted into or is received into another." Celsus deplored these experiments. "I believe that medicine should be ra­tional. . . . But to open the bodies of men still alive is as cruel as it is needless." Further advances in physiology came from the dissec­tion of dead animals and live ones.

The busiest dissector and vivisector in Rome was the second‑century physician Galen. Though he never cut up ants, gnats, fleas, "and other minuscule creatures," Galen did manage to dissect the remain­der of the animal kingdom: apes, horses, asses, mules, cows, camels, sheep, Eons, wolves, dogs, lynxes, stags, bears, weasels, mice, snakes, a variety of fish and birds, and several elephants.

Galen limited dissection of live animals to pigs or goats, which he strapped to a board. Although he obtained much anatomical infor­mation from the barbary ape, he usually would not vivisect this little tailless creature, and recommended to other scientists that they "leave live apes alone." Perhaps the ape's facial expressions and cries while being cut up were human enough to be disturbing.

From his animal studies Galen managed to learn a few funda­mental facts about how the body works. In one experiment, he cut the recurrent laryngeal nerve of a live pig and found that the animal could no longer squeal, thus identifying the origin of the voice and part of its control mechanism. Even more elegant was his identifica­tion of the optic nerve as being responsible for vision:

"When you have divided the frontal bone . . . you will be met by two nerves that go to the eye. If you divide the larger of the two, then the visual sense of the animal will be impaired. . . . But that the animal can no longer see . . . you can only appraise by deduc­tion, from the fact that you find that it does not blink with its eye at anything which you bring near it, pretending to be about to stab home with it."

Galen also made the first correct observations of the functions of the spinal cord and the kidney. He noted that if the cord is cut "behind the first thoracic rib, then that damages the hand of the ape. And should the cut follow a line behind the second thoracic rib, then that does not damage the arm, except that the skin of the ax­illary cavity and upper arm become deprived of sensibility." In an­other experiment, the ureter of a living animal was tied, proving that urine is produced in the kidney.

Galen should have stopped here, but he didn't. In­stead, he tried to use what he had found and what he could contrive to explain one of the oldest of all mysteries: what the heart does, and why it is necessary to breathe, He failed, and fifteen centuries elapsed before this interaction of muscle and blood was understood-‑the first triumph of the science of healing.

Of Pumps and Valves

A single scientist, William Harvey, made the discovery of the circulation of the blood. Even today, more than three hundred years later, Harvey's finding is considered the most important ad­vance in all of physiology, on a par with Isaac Newton's discovery of uni­versal gravitation in physics. Our knowledge of the spread of infec­tions and of the cause of many diseases depends on comprehension of blood circulation; without this comprehension, most of medicine as we know it today would not exist and doctors would be little more than witch doctors.

The recognition that the heart and blood are necessary for life is a primitive one. An association between cold, pallor, bloodlessness, and death has been common knowledge since antiquity. Vampires were believed to kill a victim by sucking out his blood, and the bloodiest of all wounds, a heart wound, was known to be invariably fatal.

The first detailed anatomic study of the heart was made around 400 B.C. and is included in a collection of ancient Greek medical treatises known as the Hippocratic corpus. The author, perhaps a Greek from Sicily, dissected the mammalian heart with exceptional skill, and though he saw it as having only two chambers rather than the four we know today, he discovered within it two interesting sets of membranes. There are two great vessels, he wrote, and "at the en­trance of each are arranged three membranes, rounded at their ex­tremities, in the shape of a half circle; and when they come together, it is marvelous to see how they close their orifices. . . . And if someone . . . takes the heart after death, and the membranes are spread out and made to lean against each other, water poured in will not penetrate into the heart, nor will air blown in; and this especially on the left; for that side has been constructed more precisely, as it should be, since the intelligence of man lies in the left cavity."

The membranes this unknown anatomist describes are the aortic and pulmonary valves. He obviously interprets them as static safety devices to prevent a messy mixing of blood and intelli­gence, testing his conclusion by pouring water into the stumps of the aorta and pulmonary artery to check whether the valves close prop­erly; this is now routine in modern pathology. But he goes further by blowing into the severed vessels, a procedure not taught in pathology residencies today.

About 270 B.C., an Alexandrian physician, Erasistratos, made the next contribution to cardiac physiology. Erasistratos discov­ered that the heart is not a static reservoir. It is a pump, with the right and left portions subdivided into upper and lower chambers (atrium and ventricle) separated by the bicuspid and tricuspid valves. These valves are made respectively of two and three roughly triangular flaps, anchored to the inner surface of the heart by cords. When the heart contracts, the valve flaps are pressed together to pre­vent blood from returning to the upper chambers. Erasistratos con­cluded correctly from his observations that the heart must receive blood from the veins and pump it out through the arteries.

Where the blood came from and went remained a mys­tery. Veins and arteries were seen as sets of independent, dead‑end canals. Blood and air were supposed to seep slowly toward the pe­riphery, where they were used up. The lungs were considered to be chiefly for the purpose of cooling the blood. Galen recognized that the arteries contained blood, and not air as had been believed, but he still managed to explain the nature of the pulse beat incorrectly, and his faulty explanation was perpetuated by his writings for nearly fifteen hundred years.

Andreas Vesalius, a professor of surgery and anatomy at the University of Padua, finally published a correct description of the anatomy of the heart in 1543. In his book De Humani Corporis Fabrica, Vesalius showed that Galen had made two serious mistakes. The ascending vena cava, which Galen had originating in the liver, was demonstrated to be one of the two great veins which bring blood from the body back to the right side of the heart. Perhaps Galen had confused the vena cava with the hepatic vein, which does arise from the liver.

Galen's description of the septum dividing the right side of the heart from the left was also incorrect, for he somehow believed that it had openings connecting the two ventricles. How Galen could have arrived at this conclusion remains uncertain. Some abnormal hearts do have a septal opening, and surgeons today correct this problem by sewing a dacron patch over it. Galen might have noted such an orifice in one or two animal hearts and regarded it as the norm. Vesalius, however, was able to show conclusively that the cardiac septum contains no openings.

For rectifying these and other mistakes Galen had made, Vesalius was showered with a torrent of abuse by his contemporaries. Jacobus Sylvius, a former teacher, turned against his pupil angrily, calling Vesalius a madman. A former assistant, Realdus Colombo, sought to discredit and deride his teacher. Vesalius was sensitive to such criticism; out of rage and disappointment he was reported to have burned notes being prepared for another publication.

Within a few years the findings of Vesalius had been verified. And when combined with the work of two other men, Ser­vetus and Colombo, they formed the anatomic basis for understanding blood circulation.

Miguel Servetus was a fellow student with Vesalius in Paris. At some period during his life as a physician he began to study the lungs and realized that blood filtered through them, mixed with air, changed color, and entered the left side of the heart. Servetus turned his attention to religion and wrote a book critical of the holy Trinity. Persecuted, he fled to Geneva, hoping to find pro­tection with another fellow student from Paris, the reformer John Calvin. But Calvin was not sympathetic and had him tried and con­demned for heresy. Servetus was burned at the stake in 1553, sup­posedly with all copies of his works. Three did escape the flames, though we are uncertain as to whether his anatomical ideas were im­mediately appreciated.

Another anatomist working at the same time as Servetus, Realdus Colombo, also observed the circulation of blood through the lungs and the mixing there with air, and in addition noted the simultaneous beat of the two ventricles of the heart. Colombo published his findings in a book that appeared in the year of his death, 1559.

Now the anatomical information necessary for understanding the circulation of the blood was available, and the parallels with New­ton's accomplishment, which occurred in the same century as Wil­liam Harvey's, can be seen. Newton was able to take Johannes Kepler's laws of planetary motion, combine them with Galileo's laws of the motion of a falling body, and from these derive the notion of universal gravita­tion. Harvey was able to take the isolated facts known about the cardiovascular system and use them to explain just how this system works. In doing so, he laid the scientific basis for all of modern medi­cine.

William Harvey was born at Folkestone, in England, April 1, 1578. He was the eldest child in the large family of Thomas Harvey, a prosperous merchant and civic official. Several brothers became successful merchants, but William's scholarly nature destined him early in life for one of the professions. The scholarliness was still in evidence years later: While accompanying King Charles I and taking care of the princes during the battle of Edgehill, Harvey is described as sitting at the outskirts of the fight under a hedge reading a book.

Harvey was sent to King's School at Canterbury and then to Caius College at Cambridge, where he received the Bachelor of Arts degree in 1597. Shortly afterward, he enrolled at the medical school of the University of Padua. Here, where Vesalius had written his book, another anatomist, Fabricius of Aquapendente, was at the peak of a distinguished career, lecturing in the windowless, six-­tiered, oval amphitheater he had had specially designed for teaching anatomy. By candlelight, Harvey and several hundred other students stood and watched as the master dissected, disposing quickly of the unpreserved corpses to prevent their reek from overpowering every­one in the closed room. Years later, Harvey was to credit Fabricius with the discovery that first inspired the young anatomy student to consider the circulation of the blood. This was the identification of the venous valves.

Actually, Johannes Baptista Cannanus, a contemporary of Vesa­lius, had observed the little venous valves long before Fabricius. But the first meticulous descriptions were not made until Fabri­cius published his book devoted to the subject, De Venarum Ostiolis. In this work, the structure, position, and distribution of the little valves are carefully noted and illustrated by fairly good drawings. Fabricius also clearly recognized that the valves offer opposition to the flow of blood from the heart towards the periphery, but failed to comprehend their true function of preventing retrograde flow, believ­ing instead that they merely prevented too much blood from being heaped in one place. Harvey did not make this mistake.

After receiving the Doctor of Medicine degree from the University of Padua in 1602, Harvey returned to England, and in the same year was awarded another doctoral degree in medicine from Cambridge. He then settled in London to practice medicine, and was admitted as a candidate to the College of Physicians in 1604. In November of that year he married Elizabeth Browne, daughter of Lancelot Browne, former first physician to Queen Elizabeth.

What sort of man was this rising young doctor? Like Shakespeare, his contemporary, Harvey left us his works but not very much about himself. Most of our knowledge about his character derives from a li­brarian and biographer, John Aubrey. Harvey, wrote Aubrey, was a very short man with a "little eie, round, very black, full of spirit." He was temperamental and somewhat eccentric. As a young man he wore a dagger, in the fashion of the day, but was prone to draw it upon the slightest provocation. In his later years he liked to be in the dark because, he said, he could think better, and had underground caves constructed at his house in Surrey for meditation.

We do not know when Harvey began to form his notion of the cir­culation of the blood. His first musings on the subject appeared in a series of anatomical lectures that he delivered in 1616. His ninety-eight-page set of notes still exists, and besides his genius these dem­onstrate that Harvey was a copious scribbler. He wrote hastily and almost illegibly in a mixture of Latin and English, and was a careless speller. In one place in his notes the word "piggg" appears, with a rather large number of g's even for seventeenth‑century English.

His writings tell us that Harvey was initially quite overwhelmed by the enormous complexity of the cardiovascular system:

"When I first gave my mind to vivisections, as a means of dis­covering the motions and uses of the heart, and sought to discover these from actual inspection, and not from the writings of others, I found the task so truly arduous, so full of difficulties, that I was al­most tempted to think . . . that the motion of the heart was only to be comprehended by God. For I could neither rightly perceive at first when the systole [contraction] and when the diastole [relaxation] took place, nor when and where dilatation and contraction occurred, by reason of the rapidity of the motion, which in many animals is ac­complished in the twinkling of an eye, coming and going like a flash of lightning; so that the systole presented itself to me now from this point, now from that; the diastole the same; and then everything was reversed, the motions occurring, as it seemed, variously and con­fusedly together. My mind was therefore greatly unsettled, nor did I know what I should myself conclude, nor what to believe from others. . . ."

Harvey solved the problem with a set of ingenious experiments. Though in some his calculations were incorrect, he managed to come to the right conclusions. There can be no doubt that Harvey had realized what he was going to find before he formally began to look for it.

The first step was to prove that the amount of blood transmitted from the veins to the arteries is so copious that all the blood in the body must pass through the heart in a short time. Physicians since Galen had erroneously believed that blood was constantly being produced from food consumed. To accomplish his proof, Harvey attempted to measure the amount of blood that the heart ejects with each beat and to establish the pulse rate.

Even today, the measurement of cardiac output is a complex and difficult procedure, and there are wide variations in results obtained by various methods. It is not surprising, then, that Harvey's measure­ments were not correct; but he arrived at a ridiculous figure, far below the lowest estimate used today. No doubt he was not a skilled experimenter.

Harvey derived his results by measuring the volume of the left ventricle in one cadaver, then multi­plying this figure by the pulse rate. But, in the first place, he meas­ured the volume incorrectly, and then he made an enormous error by using a pulse rate of thirty‑three beats per minute, about half the ac­tual average rate. The final figure he obtained for cardiac output is less than one thirty‑sixth of the lowest value accepted today. None­theless, Harvey had proved his point, because even by his calcula­tions the output of the heart in thirty minutes far exceeded the total weight of blood in the body. Obviously Galen had been quite wrong in believing that the amount of food a man eats could produce blood continuously in any such volume.

The second step of Harvey's proof was to demonstrate that the amount of blood going to the extremities is much more than is needed for the nutrition of the body. Here he used no specific meas­urements and argued instead largely by inference. In doing so, he made the important point that the blood must pass from the arteries to the veins in the extremities. This was ingeniously demonstrated by employing a bandage in such a way as to stop the flow in the veins of a man's arm while leaving the arteries open. As a result, the veins swelled but not the arteries. When the pressure was increased sufficiently to cut off arterial circulation as well, the veins did not swell. From his observations, Harvey reasoned correctly that the blood entered the extremities through the arteries and passed some­how to the veins. He looked for the channels of connection but, lack­ing a microscope, failed to find them. In 1661, four years after Harvey's death, Marcello Malpighi, using a crude microscope, located these tiny channels we now call capillaries in the lung of a frog.

The third step was to prove that blood in the veins flows toward the heart and not away from it, as Galen had believed. Harvey dem­onstrated this in an elegantly simple manner: He pressed one finger on a vein in a man's arm and moved the finger along the vein from below one valve to above the next. The blood thus pushed up the vein did not return to the emptied section. This established beyond doubt that the valves were one‑way devices, thus destroying Galen's old theory that blood moved back and forth in the venous system like the ebb and flow of the tide.

In 1628 Harvey published his experiments in a little book entitled Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus­ "An Anatomical Treatise on the Movement of the Heart and Blood in Animals" or De Motu Cordis. Here are his conclusions, soon destined to change the course of all medical thought:


"Since all things, both argument and ocular demonstration, show that the blood passes through the lungs and heart by force of the ventricles, and is sent for distribution to all parts of the body, where it makes its way into the veins and pores of the flesh, and then flows by the veins from the circumference on every side to the centre from the lesser to the greater veins, and is by them finally discharged into the vena cava and right auricle of the heart, and this in such quantity or in such afflux and reflux, thither by the arteries, hither by the veins, as cannot possibly be supplied by the ingesta, and is much greater than can be required for mere purposes of nutrition; it is ab­solutely necessary to conclude that the blood in the animal body is impelled in a circle, and is in a state of ceaseless movement; that this is the act or function which the heart performs by means of its pulse, and that it is the sole and only end of the movement and contraction of the heart."


Harvey probably never had any notion of the far‑reaching conse­quences his discovery would have. Nothing else can explain the lack of care devoted to De Motu Cordis. The manuscript was sent to an obscure German printer, Wilhelm Fitzer of Frankfurt‑am‑Main, and was produced on thin, cheap paper that quickly deteriorated. The finished work teemed with typographical errors, suggesting that Harvey did not even take the trouble to read proof. Except for the title page and two plates borrowed from Fabricius, there were no illustrations. But there was no lack of controversy.

The loudest critics were Jean Riolan, an anatomist on the faculty of the University of Paris, and his English student James Primrose. Riolan managed to induce his university to prohibit the teaching of Harvey's doctrine. Primrose, who had just been certified to practice medicine in England the year before with Harvey as one of his exam­iners, locked himself in a room for two weeks and produced quite a large book that refuted De Motu Cordis by rehashing all the old ideas. Harvey began to be referred to in some circles as "Circulator" ‑-in the Latin sense of the word, which means quack. He preserved a stoic silence and in the end lived to see his work vindicated. In the meantime, his professional standing was quite unaffected because of his royal patrons.

This patronage began in 1609, when his brother John Harvey, who had obtained employment in the king's household, influenced James I to recommend William for an appointment at St. Bartholo­mew's Hospital as assistant physician. When the physician died in the summer of that year, Harvey succeeded him. The hospital at that time had about two hundred beds for patients in twelve wards, and the new physician's duties consisted of attending in the hall of the hospital for at least one day a week throughout the year and pre­scribing for treatment at any other time when specially needed. The physician was usually expected to live within the hospital grounds, but the rule was waived for Harvey since he lived not far away. He received an annual salary of twenty‑five pounds, with two pounds extra for livery and a further eight pounds since he did not use the official residence. Three surgeons and an apothecary in charge of the dispensary formed the remainder of the staff.

In his free time, Harvey developed a large private practice, attend­ing many of the most distinguished citizens, including Sir Francis Bacon and, after about 1618, King James himself as physician ex­traordinary. Though advanced in his physiologic views, Harvey was quite conservative in the remedies he prescribed for his patients; con­sidering the wealth of worthless drugs and primitive state of medical therapeutics, such conservatism was probably best.

In 1625 King James fell ill for the last time, and Harvey led the team of doctors in attendance. After the king's death, a rumor quickly spread that his favorite, the Duke of Buckingham, had has­tened the fatal outcome by applying remedies not approved by the doctors. As suspicion grew, the duke was actually accused of having poisoned the king, and in 1626 an inquiry was ordered by Parliament. Harvey was the most important witness of several who contrib­uted to saving the duke's neck.

What may be called the best years of Harvey's life began with the ascent of the new king, Charles I. The appointment as physician ex­traordinary was continued, and Harvey received a special award for the care he had given the previous monarch. The new king and his physician quickly became the closest of friends, with the king always ready to help in furthering the biologic research. Harvey, in return, delighted in showing Charles anything of scientific interest. On one occasion a courtier received a severe chest injury that exposed his heart. Harvey was called to attend and he summoned the king, who was permitted to stick his fingers into the wound to feel the beating heart. If infection subsequently developed, at least the organisms were royal.

Harvey might have lived the rest of his days as a close confidant of the king with an excellent position but for the Civil War in England. Like many scientists before and since, Harvey had little interest in politics, but he was soon to learn how a changed political climate could so sour his life as to make it barely tolerable.

Parliament had become quite restive under Elizabeth, though de­ferring to her as an aging woman and a national symbol. Neither James I nor his son Charles was to have this good fortune. Parlia­ment would not grant either of these rulers adequate revenue, be­cause it distrusted them both. Many members were Puritans, dis­satisfied with the organization and doctrine of the Church of England. And Parliament was organized so that it could make resist­ance effective.

In 1629 the king and Parliament came to a deadlock. Charles at­tempted to rule without Parliament, which could legally meet only at the royal summons. The Scots were the first to rebel, rioting in Edin­burgh in 1637 against attempts to impose the Anglican religion in Scotland. To raise funds to put down the Scottish rebellion, Charles convoked the English Parliament in 1640, for the first time in eleven years. When it proved hostile to him, he dissolved it and called for new elections. The same men were returned. The resulting body, since it sat theoretically for the next twenty years without new elections, is known historically as the Long Parliament.

The Long Parliament, far from assisting the king against the Scots used the Scottish rebellion as a means of pressing its own demands. These were revolutionary from the outset. Parliament insisted that the chief royal advisers‑-Harvey was one-‑be not merely removed but impeached and put to death. In 1642 Parliament and king came to open war.

At the start of this civil war, Harvey was with the king. When Charles later established his headquarters at Oxford, Harvey re­mained with him, and in 1645 was made warden of Merton College. Here he resumed the work on embryology that he had begun years earlier with deer embryos, which was to result in the publication of his second book, De Generatione Animalium; or, Anatomical Excitations, Concerning the Generation of Living Creatures. But while he puttered with eggs and yolks, a powerful leader was coming to the fore.

This was a hitherto unknown gentleman named Oliver Cromwell, a devout Puritan and member of the parliamentary forces called Roundheads, from the close haircuts they wore. Cromwell was able to organize a new and more effective military force, the Ironsides, in which extreme Protestant exaltation provided the basis for morale, discipline, and the will to fight. Gradually these men were able to crush the Royalist opposition.

Cromwell concluded that the defeated King Charles could not be trusted, that "ungodly" persons of all kinds put their hopes in him (what later ages would call counterrevolution), and that be must be put to death. Since Parliament resisted, Cromwell, with the support of the army, broke Parliament up.

When the defeated Charles fled from Oxford to surrender himself to the Scots, Harvey joined him for a time at Newcastle but was forced to leave the king when he was handed over to the parlia­mentary army, and was not allowed to go to him when he was im­prisoned in the Isle of Wight. Charles' execution in 1649 left Harvey a broken and unhappy man, though even before this he had begun to suffer the consequences of having supported the wrong faction.

In 1643 he had been stripped of the post at St. Bartholomew's Hospital, one he had occupied for thirty‑four years. His professional reputation was gradually eroded, and in his last years under Crom­well's Protectorate he was regarded as a political "delinquent," being forced to spend much of his time lodging in one or another of his brothers' houses outside London. During the Civil War his house was sacked and parliamentary sol­diers destroyed most of his papers. The once‑prominent physician was reduced at the end almost to incompetence in the eyes of his patients, as one, the Lady Anne Conway, describes in a letter to a friend:

"I heare that you have a great good opinion of Dr, Harvey. I thinke you do well . . .: he is a most excellent anatomist, and I conceive that to be his Masterpiece, which knowledge is many times of great use in consultations, but in the practicke parte of Physicke I conceive him to be too mutch, many times governed by his Phantasy, the excellency and strength whereof did produce his two workes to the world. . . .

"I grieve much Dearest that you are not yet out of Dr. Harvey's hands. . . .

"When once I have ended my tryalles of Dr. Harvey which I thinke will be very shortly. He is very ill himselfe of the gowte al­most continually, and that must needs indispose him to the mindings of such things as relates not to his owne perticuler (yet he pretends very much to study and lay my case to heart)."

Another colleague put the matter more succinctly: "I know sev­eral practitioners that would not have given threepence for one of his bills."

Deeply despondent, racked with pain by gout and kidney stones, Harvey at age eighty was forced to move once again, this time to his brother Eliab Harvey's house at Roehampton. There he awoke one morning, partially paralyzed and unable to speak, and shortly after, on June 3, 1657, he died.


The Flower of English Medicine

At the time of Harvey's death his discovery was still only of theoretical interest. What, after all, could a physician offer a patient whose heart was not contracting properly? This question probably never even occurred to Harvey, because no one at the time recognized the relationship between heart disease and dropsy, a condition in which the tissues and cavities of the body fill up with fluid, frequently on account of a weak heart.

The supreme discovery in the field of cardiology was the identification of digitalis, a drug so effective for treating a weakened heart muscle that doctors have found no better substitute in two hundred years. The discoverer was an English physician, William With­ering.

For centuries the common form of dropsy, now called cardiac edema, was one of the most frequent causes of death, and an un­pleasant death it was. Dr. Samuel Johnson, the eighteenth‑cen­tury lexicographer, died of dropsy after suffering intensely, his legs becoming so painfully bloated that his physicians vainly tried to let the fluid out by making large knife incisions.

Yet since antiquity a few rather bizarre and unreliable concoctions sometimes helped a patient with dropsy. The dried bulb of the squill, a plant of the lily family native to the Mediterranean area, was known as a medicine to the ancient Egyptians and is mentioned in the Ebers Papyrus, written around 1500 B.C. The Romans used squill to treat dropsy, to strengthen the heart, to induce vomiting, and—­ominously-‑to poison rats, for the effective ingredient in squill, called a cardiac glycoside, will accomplish all these functions as the dose is increased. Strophanthus, the seeds of a genus of African shrubs and woody vines used to make arrow poison, contains another cardiac glycoside and was also introduced into medicine. The Chinese have used the dried skin of the common toad for centuries as a drug. Called ch'an su, it was highly recommended for toothache and bleeding of the gums, as well as dropsy. We now know that ch'an su contains epinephrine, an arterial constrictor, combined with a cardiac glycoside. The beneficial effects of ch'an su were also known to the peasants of Western Europe, who had used powdered toad skins medicinally for centuries.

These same peasants favored one folk remedy above all others. This medicine came from a tall plant with long pointed leaves and lovely, delicate purple flowers shaped like bells. For centuries it had grown wild through most of Europe, and its dried, powdered leaves were known to bring relief to many dropsy ­sufferers. This plant was Digitalis purpurea, the purple foxglove.[1]

We know that digitalis had been used since at least the thirteenth century by Welsh physicians, for they mentioned it in their writings as menygellydon, which means "elves gloves." The word foxglove is of uncertain origin, but some etymologists believe it is derived from the name of an ancient musical instrument that consisted of bells hung from an arched support; very likely the little purple bell‑shaped flowers hanging from the foxglove stalk looked similar. Even the Norwegian word for foxglove means "fox music."

In 1542 the, first accurate scientific description of foxglove was given by a German botanist, Leonhard Fuchs. He named the plant genus Digitalis, from the Latin digitus, meaning "finger"; but why he chose this word is uncertain. Perhaps the German name for the plant, Fingerhut, meaning "thimble," was the origin. More likely, the tall, fingerlike vertical stalk from which the foxglove flowers hang suggested the word.

Fuchs did more than name Digitalis purpurea. In his 1542 history of plants, he categorized digitalis as being of value in inducing vomit­ing and "in its action to thin, to dry up, to purge, and to free of ob­structions." John Gerard confirmed one of these observations in 1597, noting that he had used foxglove to induce vomiting. More im­portant, the plant's value in treating dropsy was noted a few years after Fuchs's account by the Dutch medical biologist Rembert Dodoens, who wrote that "for those who have water in the belly . . . it draws off the watery fluid, purifies the choleric fluid, and opens the obstruction."

Digitalis had been included in the London Pharmacopoeia by 1661, though recommended for the wrong purposes, for epilepsy and sedation. And a few years later an English physician, William Salmon, became convinced that digitalis was the long‑sought treat­ment for tuberculosis.

Salmon's error was a logical one at the time, since there was still confusion between pulmonary tuberculosis, where digi­talis is of no value, and pulmonary edema or fluid in the lungs due to heart failure, which can be dramatically helped by digitalis. When an eighteenth‑century physician administered digitalis to a patient with pulmonary edema thinking the patient had tuberculosis, and the pa­tient's condition improved, no conclusion could be more obvious than that here was a remedy for tuberculosis. This mix-up between pulmonary tuberculosis and pulmonary edema persisted well into the nineteenth century.

No confusion, however, existed in Salmon's mind about the side effects and toxicity of digitalis when given in excessive amounts. For this reason he recommended that the drug be given only in very small doses. When doctors ignored this advice and subsequently killed patients with digitalis, the Dutch physician Hermann Boerhaave, one of the most respected men in eighteenth‑century Europe, de­clared that digitalis was a poison and cautioned against its use.

The most crushing indictment of digitalis came with the experi­ments of a Dr. Salerne of Orleans in 1748. Hearing that a turkey had died after eating foxglove, Salerne proceeded to stuff foxglove powder down the throats of two healthy turkeys in the vigorous man­ner that Frenchmen usually reserve for geese in the making of pâté de foie gras. The two turkeys did not survive these ministrations, and an autopsy revealed that their intestines had been squeezed as dry as grapes in a wine press.

Salerne should have concluded that digitalis was indeed a good drug for ridding the body of excess fluid, but instead be reported to the French Academy of Sciences that the compound was a powerful poison. The Academy, at that time the final authority in European medicine, condemned the use of digitalis in medical practice, and here matters stood for a quarter century until William Withering de­cided to reinvestigate the subject.

Withering was born in 1741 into a family of distinguished physi­cians. His maternal grandfather had delivered Samuel Johnson, and his father was a successful physician at Wellington in Shropshire. William was afforded the impeccable education of the English upper class, which included mathematics, the classical languages, geogra­phy, and history. He was an average student and showed no sign in school of the remarkable insight that was to result in his dis­covery.

At the age of twenty‑one Withering decided to study medicine, and entered the University of Edinburgh, a school which had appeal for English students in the eighteenth and nineteenth centuries. Ox­ford and Cambridge had degenerated into shadows of their former selves, becoming chiefly schools for the training of clergymen. The historian Edward Gibbon had left Oxford in disgust after one year because he found his tutors "plunged deep in port and preju­dice." But the Edinburgh faculty was superb, numbering among its members some of the prominent scientists of the day.

Withering made many warm friends at Edinburgh, and throughout his life continued to correspond with teachers and classmates of his student days. He learned to play golf on the Scottish greens, and also became an accomplished musician with an incredible mas­tery of the German flute, the harpsichord, and the bagpipes. He took his degree of doctor of physic on July 31, 1766, after a successful defense of an inaugural dissertation on malignant putrid sore throat, later published under the title De Angina Gangrenosa.

In the eighteenth century no fashionable young English gentleman could consider his formal education complete until he had made the de rigueur trip to the Continent. Withering made such a journey dur­ing the summer and autumn of 1766 with a companion, a Mr. Townsend, described as "a gentleman of independent fortune familiar with the manners and language of the French." Midway through the trip Mr. Townsend had a bit of bad luck, described by Withering in a note to his parents: "I have been so much taken up for some days past that it was impossible to find time to write; I have lost my Fellow traveller Mr. Townsend; an abscess formed upon his shoul­der, a Fever came on, the wound gangren'd and yesterday he died." This was the frequent result of an infection before the days of antibiotics.

After arriving home at Christmas, Withering began to consider the matter of setting himself up in a general practice. Flattering offers came from Chester and Coventry, but he finally selected the small town of Stafford, county seat of Staffordshire. This was a spot fairly near home, where the medical reputation both of his father and his un­cles was well known. He became physician to the newly built infirmary, and though he was well liked, the people of the community were slow to accept a newcomer, leaving free time for the new doctor to fill.

Withering chose to occupy this time engaged in the study of bot­any, and for a romantic reason. As a student he had detested the subject, speaking of "the disagreeable ideas I have formed of the study of botany." But one of his first Stafford patients was a charm­ing young woman, Helena Cooke, whom it was necessary to visit al­most daily. Miss Cooke passed the hours of her long convalescence by painting flowers, and Withering fell into the habit of searching the countryside for new specimens. Her style was so admired that on September 17, 1772, Miss Cooke became Mrs. Withering.

Along with a new wife, Withering had managed to acquire a first­ rate knowledge of plants, and he soon published A Botanical Ar­rangement of All the Vegetables Naturally Grown in Great Britain According to the System of the Celebrated Linnaeus, still considered a classic text. One particular section is of interest today, be­cause it contains the first cautious comments on the medicinal prop­erties of the foxglove: "A dram of it taken inwardly excites violent vomiting. It is certainly a very active medicine and merits more at­tention than modern practice bestows on it."

The study of foxglove that made Withering’s reputation was prompted by a medical consultation: "In the year 1775, my opinion was asked concerning a family receipt for the cure of the dropsy. I was told that it had long been kept a secret by an old woman in Shropshire, who had sometimes made cures after the more regular practitioners had failed. I was informed also, that the effects pro­duced were violent vomiting and purging; for the diuretic effects seemed to have been overlooked. The medicine was composed of twenty or more different herbs; but it was not very difficult for one conversant in these subjects, to perceive, that the active herb could be no other than the Foxglove."

The diuretic effect referred to is the one so valuable in the treat­ment of dropsy, for when it occurs, the body rids itself of copious quantities of unwanted fluid through the kidneys. Withering noted this beneficial action in a few patients he treated in Stafford, but pres­ently another opportunity to use digitalis arose. An offer came from Erasmus Darwin, grandfather of Charles Darwin, to sponsor a practice in Birmingham, and Withering was soon busier than ever be­fore with dropsy cases. Here is a record of the remarkable results in one, a Miss Hill of Aston, who was in the last stages of heart failure with extreme shortness of breath when a liquid digitalis preparation was administered by mouth:

"The patient took five . . . draughts, which made her very sick, and acted very powerfully on the kidneys, for within the first twenty­-four hours she made upwards of eight quarts of water. The sense of fullness and oppression across her stomach was greatly diminished, her breath was eased, her pulse became more full and regular, and the swellings of her legs subsided.

"26th. Our patient being thus snatched from impending destruc­tion, Dr. Darwin proposed to give her a decoction of pareira brava and guaiacum shavings, with pills of myrrh and white vitriol; and if costive, a pill with calomel and aloes. To these propositions I gave a ready assent.

"30th. This day Dr. Darwin saw her, and directed a continuation of the medicines last prescribed."

This case is quite a notorious one in the history of digitalis. With­ering, writing the report nine years later, stated that when he suggested the drug, "Dr. Darwin very politely acceded immediately to my proposition and, as he had never seen it given, left the prepa­ration and dose to my direction." Yet Darwin jumped into print al­most immediately after with a paper that did not mention Withering, and forgot him again in another article, "An Account of the Success­ful Use of Foxglove in Some Dropsies and in the Pulmonary Con­sumption," published in the Medical Transactions of the College of Physicians. The two men then became bitter enemies, though Wither­ing was to retain priority for his discovery.

Darwin was not able to convince the medical profession with his two unscrupulously published works that he had found anything worthwhile. Withering managed to inaugurate the systematic use of digitalis. He kept full records of his extensive case experience, and after ten years' careful observation published in 1785 a detailed and systematic treatise, An Account of the Foxglove, and Some of its Medical Uses: with Practical Remarks on Dropsy and Other Diseases.

In this book, the fundamentals of digitalis treatment were correctly established for the first time. A dose of one or two grains twice daily was advised for patients beginning therapy, the amount still prescribed today. Withering also recognized that slow digitalization required several days to achieve. Equally important, he appreciated digitalis toxicity and cautioned against over dosage. He found that the drug was effective until evidence of its action upon "the kidneys, the stomach, the pulse, or the bowels" was apparent; then it was to be stopped. The description of an overdosed patient is most striking.

"I have lately been told that a person in the neighborhood of Warwick possesses a famous family recipe for the dropsy, in which I Foxglove is the active medicine, and a lady from the western part Yorkshire assures me that the people in her country often cure the selves of dropsical complaints by taking Foxglove tea. In confirmation of this I recollect about two years ago being desired to visit a traveling Yorkshire tradesman. I found him incessantly vomiting, vision indistinct, his pulse 40 in a minute. On enquiry it came that his wife had stewed a large handful of green foxglove leaves in half a pint of water and given him the liquor which he drank at a draught in order to cure him of an asthmatic affection. This good woman knew the medicine of her county, but not the dose of it, for her husband narrowly escaped with his life."

Especially important in the Account was Withering's brilliant recognition of the action of digitalis, "a power over the motion of the heart, to a degree yet unobserved in any other medicine." Thus did Harvey's discovery of the circulation first become applicable to a pathologic condition.

By the time the Account was published, Withering had become highly successful. His practice had grown to bring him an annual in­come of two thousand pounds per year, an immense sum at that time, despite the fact that he held a daily free clinic for the poor and is said to have treated three thousand cases annually without charge. He had also become a member of the Lunar Society, a select scientific organization that numbered among its members James Watt, inventor of the steam engine, Josiah Wedgewood, the pottery manufacturer, and Joseph Priestley, the discoverer of oxygen. Ben­jamin Franklin was a guest at one meeting, and he consulted Wither­ing by letter regarding the treatment of his kidney stones.

But just as he reached the peak of his career, Withering was struck by consumption. Two serious attacks in 1783 and 1786 forced him to give up work entirely and go to the country to regain his health. In 1790 he had a serious attack of pleurisy, and until his death he was plagued by shortness of breath and frequent coughing up of blood. To escape the damp English winters, he spent two seasons in Por­tugal, somehow finding strength to study the tropical and semi-tropical plants not seen in England.

The 1793 trip to Portugal proved to be his last. He bought a beau­tiful country estate in September 1799, but on the date he was to move in, Mrs. Withering was taken ill and could not accompany him; this, in addition to the fatigue of the journey, sent him to bed, and he died October 6, 1799. During the last days, a friend who came to see him produced the most distasteful pun in the history of medi­cine: "The flower of English medicine is indeed withering."


The Flame of Life


In 1794, five years before William Withering's quiet death in bed, another scientist had died much more violently, on the guillotine. This man, Antoine Lavoisier, demonstrated conclusively why breathing is necessary. Lavoisier, a chemist and not a physician, was able to show that breathing allows the flame of life to burn in es­sentially the same way as the flame of a candle, by combustion of carbon.

Though respiration is one of the oldest physiologic functions man has observed, for thousands of years it remained the most mysteri­ous. The eyes were necessary to see, the ears to hear, the kidneys to make urine, the heart to pump; but what did the lungs do?

The ancient Greeks thought they had the answer: The lungs some­how sucked the blood from one part of the body to another. Aristo­tle was sure he had a better idea. Noting that the lungs were well supplied with blood, he postulated that their function must be to cool the blood and produce mucus. A few years later, Erasistratos, who had brilliantly recognized the pumping function of the heart, stated that the arteries were empty pipes filled with air by the lungs. Galen rectified this error by demonstrating that the arteries contained blood and not air, but was unable to explain breathing.

So matters stood for seventeen centuries until an Englishman, Robert Boyle, began to experiment. Today every high school chemis­try student recognizes the name of this scientist in Boyle's law: The volume of a gas is inversely proportional to the pressure on it, pro­vided temperature is kept constant. But Boyle was responsible for much more, including investigation of the physics of colors, the chemistry of acids and bases, and the specific gravity of body fluids.

Boyle's work on respiration was stimulated by news of a novel in­vention. In 1650 a German, Otto von Guericke, had used a suction pump to empty a wine barrel filled with water and produce what all philosophers had believed to be impossible-‑a vacuum. Going fur­ther, Guericke pumped the air from two metal hemispheres and then amazed a large group of spectators by connecting a team of horses to each hemisphere. Straining in opposite directions, the two teams could not pull the hemispheres apart. Guericke was obviously some­thing of a showman, since he probably knew that simply anchoring one of the hemispheres to a wall could have eliminated one of the teams of horses.

When in 1657 Boyle read the first accounts of these experiments he set out to construct a similar device. The resulting pump designed by his assistant, Robert Hooke, was easily operated by one man and moderately airtight-‑the first deliberately designed air pump. Its receiver, seven to eight gallons in volume, was made of glass and fitted so that objects could be readily put into it before pumping and then could be manipulated in the vacuum.

With his new air pump, Boyle was able to carry out a large num­ber of experiments. He demonstrated how a deflated bladder swelled in the vacuum, how the mercury in a barometer fell, and how the ticking of a watch suspended by a thread grew fainter and stopped as air was removed. Most dramatic was the way a bird or kitten without air languished and eventually died in an environment that would not allow a candle to bum. Throughout the next century this fascination with the effect on animals ensured that Boyle's experiment was widely repeated by amateur scientists and is now represented by a painting in the Tate Gallery in London, "The Air Pump," by Joseph Wright of Derby. In a charming genre scene, Wright depicted an experimenter using the pump to suffocate a bird in a bell jar, while a small child looks on in horror.

Robert Hooke, working on his own, went a bit further than Boyle had. Opening widely the thorax of a dog, he demonstrated that the animal could be kept alive by artificial respiration in absence of all movements of the chest wall. This experiment had been done before, and is described in the writings of Vesalius. But Hooke ingeniously demonstrated that the animal could also be kept alive without any movement of the lung at all. To do this, the lung was kept motionless but thoroughly distended by maintaining a powerful blast with a bellows, the air driven in escaping continually through minute holes pricked in the lung. Thus the mere movement of the lungs in breath­ing, previously believed to be the essential factor, was shown to be unimportant. The purpose of breathing was to keep a supply of fresh air in constant contact with the lung tissue.

Hooke is perhaps the most eccentric figure in the history of sci­ence. He left his imprint in chemistry and physics as well as physiology. Physics students remember him for Hooke's law: The displacement of an elastic body is directly proportional to the force applied to it. He was also the foremost English microscopist. But during his lifetime visitors at­tracted by his fame must have been surprised when meeting him.

No artist or rock musician of today has a shaggier or more unkempt appearance than did Hooke. His massive uncombed mane al­most covered an ashen face, while his crooked figure and shrunken limbs grew smaller and more deformed with the years. His parsimony and his crabbed, sour, jealous, vain, and morbid character made him one of the most well‑known misers in England.

Not being satisfied to make many of the scientific discoveries of his age, Hooke also demanded the rest. When Newton's Principia was in the process of publication, Hooke so insistently claimed part of the work was stolen from him that Newton determined to suppress a third of the volume, and would have done so except for the inter­vention of Edmund Halley. Later, when Newton completed Optics, he ascertained that Hooke had claims upon it, and steadfastly refused to publish until after Hooke was dead.

When Hooke died, several thousand pounds were found in an old iron chest in the scientist’s dingy lodgings; the rusty key was said to have been unused for thirty years, though Hooke’s physiologic experiments had provided another key that was employed almost immediately.

In 1669 Richard Lower, an English physician, used Hooke's method of artificial respiration to observe the blood in the pulmonary veins-‑the vessels that go from the lungs to the heart. Lower noted that when an animal was suffocated, the blood in the pulmonary veins and the left side of the heart became dark and venous. Taking this dark blood and injecting it into the lungs, he found that it be­came bright red only if fresh air was driven through the lungs simul­taneously. He concluded correctly that the change in color was due simply to the exposure of the blood to air in the lungs. This was confirmed by the fact that a clot of dark venous blood soon became bright red on the upper surface where it had been exposed to air, and if it was turned upside down, the dark undersurface also turned bright red.

Following Lower's work, the final important seventeenth‑century observation of respiration was made by another Englishman, John Mayow. Mayow used a bell jar inverted over water in which he placed small animals, lighted candles, and combustible materials, noting that the extinction of life and flame were associated with a re­duction in volume of the contained air. Though thereby proving that only a portion of the air is necessary to support life and flame, Mayow failed to identify this portion as oxygen. Here knowledge of respiration might have remained indefinitely fixed but for the revolu­tion that was taking place in chemistry.

Chemistry had evolved from the alchemy of the Middle Ages and its preoccupation with converting metals such as lead into gold. To the alchemists, all matter was supposed to be made up of a "prima materia" modified by four elements: earth, air, fire, and water. By the eighteenth century, these had been differentiated into three varie­ties-‑mercurial, vitreous, and combustible. In addition to the ele­ments, there were four spirits-‑sulfur, mercury, arsenic, and Sal am­moniac. There were also six bodies: gold, silver, copper, lead, tin, and iron. And the "soul" of all matter was believed to be a hypo­thetical substance, phlogiston, by virtue of which all combustible bodies burned.

Joseph Priestley, the son of a weaver in the small English town of Leeds, made the first large cracks in this imposing alchemical structure. Orphaned at an early age, Priestley had been adopted by an aunt, a strong‑minded woman of independent temper, whose influence led to his ordination as a Calvinist minister who eventually adopted Unitarian views.

On a trip to London shortly after his marriage, Priestley met the philosopher from the American colonies, Benjamin Franklin, and the encounter was a turning point. Up to this time, the young minister had taken only a casual interest in science, but when he suggested to Franklin that someone ought to write a popular book on electricity, Franklin urged him to do so. The result was Priestley's brilliant work The History and Present State of Electricity. In writ­ing, he was led to investigate for himself certain disputed points of electrical theory, and, through his natural flair for research, he made some original discoveries, one of which was the fact that carbon is an excellent conductor of electricity. So successful was the book that a year after its publication Priestley was elected to the Royal Society.

Priestley's blow to the old alchemical theories came with his discovery that air is not an elementary substance. Instead, it is com­posed of several gases, one of which, oxygen, which he called "de­phlogisticated air," is the one essential to the life of animals. On August 1, 1774, he made some oxygen and was astonished at how brightly a candle burned in it. On March 8, 1775, he put a mouse into oxygen and noted how well the animal breathed in it. Shortly thereafter he wrote to Franklin, "Hitherto only two mice and myself have had the privilege of breathing it." His further experiments re­vealed that green plants breathe out oxygen in sunlight, thus providing for the animals that need it.

Though extremely conservative scientifically, Priestley was quite radical in his theological and political beliefs, and was as well a rather difficult, cold, cantankerous, precise, prim, puritanical individual. Naturally, a scientist does not achieve immortality for his pleasing personality, but in Priestley's case, a more acceptable dispo­sition and set of political convictions might have made life much smoother.

Priestley got into trouble with his support of the French Revolution, a very unpopular issue in some parts of England. In 1791, on the second anniversary of the fall of the Bastille, he had joined a group of friends to celebrate the event when a hysterical mob that had set fire to two dissident churches set out to burn down Priestley's house, hoping to be able to lynch him and his family as well. Priestley tried to bribe the leaders and, failing, took refuge with friends while the howling crowd looted his house, scattered his papers, battered down the walls, and made a bonfire of the debris.

Several hours later the mob went in search of Priestley. He and his family escaped in a coach with only a few minutes to spare, immigrat­ing to the United States not long afterward. In America he continued to be hounded by tragedy. First his favorite son died and, shortly afterward, his wife, who had never recovered from the shock of the riots. Yet Priestley did become a close friend of President Thomas Jefferson, who once told him, "Yours is one of the few lives precious to mankind."

Priestley’s contemporary at the Univer­sity of Edinburgh, Joseph Black, was a man able to engage in research unhindered by violent mobs. Studying the decomposition by heat of caustic lime, Black identified a by‑product, the gas carbon dioxide, then known as "fixed air." Jean Baptiste van Helmont had produced this substance a hun­dred years before, but Black went further by demonstrating that it was present in the expired air of man and would not support life.

Now most of the information needed to understand the process of respiration was at hand. The man who finally provided this under­standing, with theory supported by experiment, was Antoine Laurent Lavoisier.

Some scientists are facile theoreticians but poor experimenters. William Harvey, who recognized the circulation of the blood though he could not even measure the pulse rate accurately, was one such. Gregor Mendel, who perceived that individual hereditary characteristics are determined by two particles, though he very probably falsified his experimental results to prove this, was another. Two fur­ther examples are James Watson and Francis Crick, who determined the DNA structure using only chemical theory and the facts about the molecule already known.

Other scientists are skilled experi­menters without being theoreticians. Rosalind Franklin, who identified and made elegant X‑ray crystallographic studies of the A and B forms of DNA, is an example. But Lavoisier was both a superb experimentalist and a brilliant theoretician. His contribution to the science of healing is universally regarded as the most important of all those made in the eighteenth century.

Lavoisier was born in Paris on August 26, 1743, the only son of well‑to‑do parents. His mother died when he was quite young, and his father and a maiden aunt brought him up with loving care. His father wanted him to become a lawyer, and Antoine dutifully com­plied, studying law at Mazarin College, qualifying as Bachelor of Law in 1763 and as Licentiate in 1764.

A taste for science had developed in the young man. In college he had taken courses in astronomy, botany, chemistry, and geology, and upon finishing law school he quickly turned to science again. In 1765 Lavoisier published his first paper on chemistry, using a careful quantitative approach. He also won a medal from the king in a prize essay contest on metropolitan street lighting. In 1768, when he was but twenty‑five years old, he was admitted to membership in the Academy of Sciences. Soon Lavoisier was being assigned to commissions upon the recom­mendation of the eminent scientists in France, usually also writing the reports of the commissions' findings for presentation to the Acad­emy. But at just this time he made the mistake that was to cost him his head.

Because of his resolve to pursue a career in science, Lavoisier ar­ranged to assure himself of sufficient financial means by buying a part share in the Ferme Générale, a widely hated, privately owned organization to which the French monarchy farmed out a profitable tax‑gathering monopoly. Throughout his life, Lavoisier profited by his association with this organization and he seems to have been quite fair with those from whom the taxes were collected.

At age twenty‑eight, Lavoisier married Marie Anne Pierrette Paulze, the fourteen‑year‑old daughter of a prominent member of the Ferme. Though it was a marriage of convenience arranged by the fa­ther to save his daughter from marrying an elderly, disreputable nobleman, Lavoisier and his young bride proved to be a happy pair. Marie was both a gifted linguist and a skilled artist, who translated scientific works for her husband and prepared excellent illustrations of his experiments. As a hostess she made the Lavoisier home a pop­ular meeting place for French and foreign scientists. And after her husband's execution she edited and printed privately his last work, compiled in prison, Memoires de Chimie. Her life was ultimately em­bittered by an unhappy, short second marriage to Count Rumford. Rumford was a renowned scientist and inventor, but also an adven­turer possessing no patience with his wife's domestic inclinations. During one party, to show his disdain for Marie, he publicly threw a pot of boiling water over her prized bed of flowers. During such times, the former Mme. Lavoisier no doubt longed for the period during which she assisted her first husband in his experiments.

Of these, the most important are the ones Lavoisier performed at age twenty‑nine, one year after his marriage. While they were in part a repetition of Priestley's work, both men were actually performing al­most a caricature of one of the classic experiments of alchemy.

First, red oxide of mercury was heated using a burning glass, in a vessel in which the gas-produced‑oxygen could be observed and collected. This was the qualitative part of the experiment, but to Lavoisier's mind a revolutionary new idea was suggested: Run the experiment in both directions and measure exactly the quantities that are exchanged. Initially, mercury was burned so that it absorbed oxy­gen, and the exact amount of oxygen taken up from a closed vessel was determined from the difference in weight between the beginning of the burning and the end. Then the process was reversed by vigor­ously heating the mercuric oxide formed so that it would again expel the oxygen. When elemental mercury was left behind and the oxygen had flowed into the vessel, Lavoisier once more measured the proportions and found exactly the same amount of oxygen was given of as had been taken up before.

Quite suddenly, the process of chemical combination had been revealed for what it is, the coupling and uncoupling occurring between fixed quantities of two substances. Lavoisier had brilliantly dispatched the old notions of phlogiston, essences, and principles by showing that two elements, mercury and oxygen, had been demonstrably put together and taken apart. As he said, "This discovery, which I have established by experiments that I regard as decisive, has led me to think that what is observed . . . may well take place in the case of all substances that gain weight by combustion. . . ."

These new principles were slowly accepted by most scientists, though a few continued to cling to the old theory. A whole new nomenclature had to be devised, for "earth," "air," "fire," and “water" were no longer sufficient. Lavoisier, with other leading French chemists, composed this terminology, and with minor revision it is still in use today.

Early during his studies of combustion Lavoisier guessed that what had occurred in his glass beakers might also occur in the animal body. Working with the French mathematician Pierre Laplace, he de­signed a set of elegant experiments to verify this theory. By accurately measuring a guinea pig's intake of oxygen and output of carbon diox­ide and heat-‑the latter with an ice calorimeter they invented-‑the two men were able to demonstrate that the animal produced the same amount of heat during consumption of a predetermined amount of oxygen as was produced by burning charcoal consuming the same amount of oxygen. From their studies, Lavoisier and Laplace con­cluded: "Respiration is therefore a combustion, admittedly very slow, but otherwise exactly similar to that of charcoal; it takes place in the interior of the lungs, without the evolution of light, since the matter of fire set free is immediately absorbed by the moisture of those organs. . . ."

Lavoisier erred in believing that combustion took place in the lungs rather than in the tissues, but this mistake was made up for by the breadth and depth of his other in­vestigations. He was the first scientist to show that water is made of hydrogen and oxygen and is, therefore, a compound rather than an element‑-another blow to alchemy. He also made valuable contributions to the study of political economy, the science of agriculture, and public education. There is no way to guess what else this bril­liant man might have achieved had he lived longer, for the most vio­lent segment of the French Revolution tragically coincided with the peak of his scientific career.

In 1793, to repress all counterrevolution, the revolutionary gov­ernment of France, called the Convention, created a kind of supreme political police and set up what we now call "the Terror." Designed to protect the new republic from its internal enemies, the Terror struck at those who were in league against the republic, and at those who were merely suspected of hostile activities. The number of per­sons who lost their lives in the Terror, from the late summer of 1793 to July 1794, is small by twentieth‑century standards. Yet about forty thousand persons died in it, most on the guillotine, though some by other methods. At Nantes, for example, two thousand peo­ple were loaded on barges and deliberately drowned. Victims of the Terror included Marie Antoinette and other royalists, former revolu­tionaries, and Lavoisier.

The tax‑collecting Ferme Générale was, after the royal family, one of the first targets. No one then had any more love for revenue agents than we do today. On November 14, 1793, Lavoisier, his father‑in-­law, and their colleagues on the Ferme were ordered arrested. Since he had been scrupulously honest in his dealings, Lavoisier was accused of such crimes as trying to poison the Paris air by erecting a large wall in the city. When his attorney asked that consideration be given to Lavoisier's scientific achievements and their benefit to the nation, the judge, one Jean Baptiste Coffinhal, snapped back that the republic had no need for scientists.

Lavoisier, dignified and aristocratic to the end, was executed on May 8, 1794, for "plotting against the people of France." Shortly be­fore he went to the guillotine, he calmly remarked, "This probably saves me from the inconveniences of old age."

His body was dumped, along with dozens of others, into an un­marked mass grave.

[1] Chinese physicians also recognized that Digitalis purpurea could be used to treat tumors. Modern studies have demonstrated that digoxin and digitoxin are of value in the treatment of brain, blood, breast, and prostate cancer and work by causing apoptosis, that is, cell death by self destruction. (Haux J. Digitoxin is a potential anticancer agent for several types of cancer. Medical Hypotheses 53:543-548, 1999)