In the ancient world, Alexandria, the city in Egypt named for Alexander the Great (356–323 B.C.E.), represented wealth and stability, a fusion of the ancient lore of Egypt and the most dynamic elements of Greek civi- lization. Among the greatest treasures of the city were its museum and library. The scholars who worked at the museum and library, under the sponsorship of the rulers of Alexandria, participated in an unprec- edented intellectual experiment. According to some estimates, the Alexandrian library contained more than 700,000 scrolls. The librarians collected, conﬁscated, copied, and edited many manuscripts, including the texts now known as the Hippocratic collection. In discussing the authenticity of various works in the Hippocratic collection, Galen of Pergamum claimed that the rulers of Alexandria were so eager to enhance the library that they conﬁscated all books found on ships entering the harbor. Galen warned that many forgeries had been created to satisfy the Alexandrian passion for book collecting. The magniﬁcent facilities of the museum are said to have included zoological and botan- ical gardens, lecture halls, and rooms for research and teaching. To encourage the exchange of ideas, the scholars took their meals together in the great hall of the museum; the meals were free and the salary of the professors was tax exempt. Unfortunately, no contemporary accounts of the famous museum have survived and the evidence concerning the medical research conducted at the museum is ambiguous.
Many sciences ﬂourished at Alexandria, although research was primarily oriented towards ﬁelds with practical applications, such as medicine and engineering. Medical experts were expected to supervise city and army sanitation and train military doctors. Most importantly, for a brief and rare interval, the practice of human dissection was not only tolerated, but actively encouraged. Perhaps the Egyptian tradition of cutting open the body and removing certain organs as part of the embalming ritual helped overcome traditional Greek antipathy to the mutilation of corpses. Alexandrian scientists helped establish two of the major themes of Western medical theory: ﬁrst, that systematic dis- section provides essential information about structure and function; second, that this knowledge is valuable in and of itself, even if it pro- vides little or nothing of immediate practical value to clinical medicine, patient care, or public health.
Alexander the great and his physicians. As he died, Alexander allegedly said, ‘‘I am dying with the help of too many physicians.’’ For medical science, the Hellenistic period (roughly the time between the death of Alexander to about 30 B.C.E., when the Romans annexed Egypt) is most notable for the work of its most famous, or infamous, anatomists—Herophilus (ca. 330/320–260/250 B.C.E.) and Erasistratus (ca. 310–250 B.C.E.). Unfortunately, so little direct infor- mation about the Alexandrian era has been preserved that the exact relationship between these anatomists and the city of Alexandria remains obscure. Historians agree that both Herophilus and Erasistratus were skillful anatomists who eagerly exploited the opportunity to conduct studies of human bodies, but it is not clear whether anatomists of this era performed some of their studies on living human beings or conﬁned themselves to postmortems. Anatomists might also have used their patients and students as experimental subjects for less invasive research. When Christian theologians such as Tertullian and St. Augustine wanted evidence of the heinous acts committed by the pagans, they pointed to the notorious Herophilus and accused him of torturing six hundred human beings to death. The Roman encyclopedist Celsus charged Herophilus and Erasistratus with performing vivisection on condemned criminals awarded to them by the rulers of Alexandria. While these accusers were obviously not eyewitnesses, some historians have accepted their allegations; others remain skeptical.
The extent or even the existence of the practice of human vivi- section during the Alexandrian era remains controversial because the writings of Herophilus and Erasistratus have not survived and are known only through the diatribes of their enemies. Accusations made hundreds of years later cannot be taken as deﬁnitive proof, but there is no partic- ular reason to believe that the authorities would have prohibited human vivisection, especially if the victims were criminals or prisoners of war. Certainly, the well-documented atrocities committed in the twentieth century suggest that there is no limit to the human capacity for deprav- ity, whether individual or state-sponsored. Nor have the events that marked the beginning of the new millennium challenged such pessimistic conclusions. Even though conditions during the Hellenistic era made systematic anatomical research possible, human dissection was still offensive to prevailing sentiments, evoked superstitious dread, and created an evil reputation for Herophilus and Erasistratus.
Herophilus, Erasistratus, and their colleagues were engaged in constructing an entirely new science of human beings rather than an abstract philosophical system. The argument that Herophilus would not have made certain errors if he had done vivisections fails to allow for the inﬂuence of pre-existing concepts on perception and interpre- tation, and the intrinsic difﬁculty of innovative anatomical studies. Whatever conditions made the work of Herophilus and Erasistratus possible did not last long. Human dissection was probably discontinued by the end of the second century B.C.E., but Alexandrian anatomists probably continued to use human skeletons for research and teaching even after they were forced to conﬁne dissection and vivisection to other animal species.
In his investigation of the circulatory system, Herophilus noted the difference between the arteries, with their strong pulsating walls, and the veins, with their relatively weak walls. Contrary to the prevailing assumption that the veins carried blood and the arteries carried air, Herophilus stated that both kinds of vessels carried blood. Intrigued by changes in the pulse that correlated with health and disease, Herophilus tried to measure the beat of the pulse using a water clock that had been developed in Alexandria.
Apparently known as a chronic skeptic, Herophilus regarded all physiological and pathological theories as hypothetical and provisional, including Hippocratic humoralism. While he probably did not totally reject humoral pathology, he seems to have preferred a theory of four life-guiding faculties that governed the body: a nourishing faculty in the liver and digestive organs, a warming power in the heart, a sensitive or perceptive faculty in the nerves, and a rational force in the brain. In clinical practice, Herophilus seems to have favored more active inter- vention than that recommended by Hippocrates and he may have used the concept of hot–cold, moist–dry qualities as a guide to therapeutic decisions. Vigorous bloodletting and a system of complex pharmaceuti- cals became associated with Herophilean medicine, but the anatomist appears to have urged his students to familiarize themselves with dietet- ics, medicine, surgery, and obstetrics.
Little is known about Herophilus, except that he probably studied with the physician Praxagoras of Cos, and was said to be the author of more than ﬁfty books, including On Anatomy, On the Eyes, and a hand- book for midwives, but only a few excerpts of his writings have sur- vived. There is no direct evidence that Herophilus was a member of the faculty of the Alexandrian museum, or that he ever carried out any human vivisections or dissections at that institution. Nevertheless, his access to human cadavers, and perhaps live prisoners, was said to be the result of governmental support.
As a result of his extensive studies of the nervous system, including the connection between the brain, spinal cord and nerves, Herophilus rejected Aristotle’s claim that the heart was the most important organ of the body and the seat of intelligence. Herophilus argued that the brain was the center of the nervous system. He also described the diges- tive system, called attention to the variability in the shape of the liver, and differentiated between tendons and nerves.
For Herophilus, health was the greatest good. The aphorism, ‘‘Wisdom and art, strength and wealth, all are useless without health,’’ is attributed to him. He is also credited with the saying: ‘‘The best physician is the one who is able to differentiate the possible from the impossible.’’ He urged physicians to be familiar with dietetics, gymnastics, drugs, surgery, and obstetrics. As practitioners, his followers were known to favor bleeding and the aggressive use of complex drug mixtures.
According to a story often dismissed as a myth, an Athenian woman named Agnodice was one of the students afﬁliated with Herophilus. Distressed by the suffering of women who would rather die than be examined by a male physician, Agnodice disguised herself as a man in order to study medicine. Agnodice won the gratitude of her female patients, but when her subterfuge was discovered, she was prosecuted for violating laws that prohibited women from studying medicine. Her loyal patients are said to have warned her male prosecu- tors that they would be seen as the cruel enemies of womankind if they condemned to death their only female physician. Agnodice’s story has been used for hundreds of years to rally support for the education of medical women. Indeed, in writing about the diseases of women, Hippocrates had pointed to the problem epitomized in the story of Agnodice. Women were often so reluctant to discuss their problems with male physicians that simple illnesses became incurable.
When scholars of the Renaissance sought to challenge the stiﬂing authority of the ancients, especially that of Galen, the long neglected and much viliﬁed Herophilus was lauded as the ‘‘Vesalius of antiquity.’’ The title could also have applied to Erasistratus, another intriguing and rather shadowy ﬁgure, who was attacked by Galen for the unforgivable heresy of rejecting the Hippocratic philosophy of medicine. Galen wrote two books against Erasistratus and criticized his ideas whenever possi- ble. Galen claimed that Erasistratus and Herophilus were contempor- aries, but Erasistratus may have been at least thirty years younger than Herophilus. According to one biographical tradition, when Erasistratus diagnosed his own illness as an incurable cancer he committed suicide rather than suffer inexorable decline.
Like Hippocrates, Erasistratus was born into a medical family. Little is known about his life, other than his decision to give up medical practice to devote himself to the study of anatomy and physiology. In a fragment preserved by Galen, Erasistratus spoke of the joys of research and how it made the investigator ready to devote day and night to solving every aspect of a scientiﬁc problem. Ancient sources credit Erasistratus with over ﬁfty books, including specialized texts on fevers, bloodletting, paral- ysis, drugs, poisons, and dietetics. Erasistratus may have carried out his research at the court of Antiochus in Seleucia, rather than at Alexandria, but the research interests of Herophilus and Erasistratus were strikingly similar. There is, however, some indication that Erasistratus was more interested in the remote and obscure causes of disease than Herophilus. Galen accused Erasistratus of rejecting the Hippocratic philosophy of medicine and following the teachings of Aristotle. Like Herophilus, Erasistratus probably tried to replace humoral theory with a new doctrine. In the case of Erasistratus, this seems to have developed into a pathology of solids that perhaps did more to guide his anatomical research than his approach to therapeutics.
Erasistratus is said to have been a gifted practitioner who rejected the idea that a general knowledge of the body and its functioning in health was necessary to the practicing physician. Many problems, he argued, could be prevented or treated with simple remedies and hygienic living. Nevertheless, he believed in studying pathological anatomy as a key to localized causes of disease. He was particularly interested in the possibility that disease and inﬂammation were caused by the accumu- lation of a localized plethora of blood that forced blood to pass from the veins into the arteries. Skeptical of many standard therapeutic meth- ods and Hippocratic humorology, Erasistratus invoked a mechanical, localized concept of physiological and pathological phenomena based on the atomic theory of Democritus. Like the founder of atomic theory, Erasistratus was apparently willing to speculate about the existence of unseen entities. Having traced the veins, arteries, and nerves to the ﬁnest subdivisions visible to the naked eye, Erasistratus postulated further ramiﬁcations beyond the limits of vision. The invisible fabric of the body, according to Erasistratus, was made up of a threefold network composed of veins, arteries, and nerves. To complete his picture of the ﬁne structure of the body, Erasistratus proposed the existence of parenchyma (material poured in between the network of vessels).
Perhaps because of his theory that disease was caused by a local excess of blood, Erasistratus paid particular attention to the heart, veins, and arteries. In his lost treatises, he apparently gave a detailed description of the heart, including the semilunar, tricuspid, and bicuspid valves. Mechanical analogies, dissections, and perhaps vivisection experiments suggested to Erasistratus that the heart could be seen as a pump in which certain ‘‘membranes’’ served as the ﬂap valves. Using a combination of logic, intuition, and imagination, Erasistratus traced the veins, arteries, and nerves to the ﬁnest subdivisions visible to the naked eye and speculated about further subdivisions beyond the limits of vision. He also gave a detailed description of the liver and gallblad- der, and initiated a study of the lacteals that was not improved upon until the work of Gasparo Aselli (1581–1626).
Erasistratus accepted the traditional idea that the function of the arteries was to carry pneuma (air) rather than blood. The veins, which supposedly arose from the liver, and the arteries, which were thought to arise from the heart, were generally thought of as independent sys- tems of dead-end canals through which blood and pneuma seeped slowly to the periphery of the body so that each part of the body could draw out its proper nourishment. He realized, however, that anatomists had to account for the fact that blood, which was supposed to be carried by the veins, spurted out of torn arteries. In order to rationalize the inconsistencies in this system, Erasistratus argued that although the veins and arteries were functionally separate in healthy, intact individ- uals, there were tiny collapsed or closed connections between the two kinds of vessels. When an artery was damaged, air escaped and venous blood was forced through the connections between the veins and arteries, because—as Aristotle taught—nature abhorred a vacuum. In other words, the presence of blood in the arteries was the result of an injury or some other pathological condition. Observations of engorged veins and collapsed arteries in the cadaver would appear to support these ideas.
Erasistratus concluded that disease was due to plethora, that is, an excess of blood from undigested foods that tended to become putrid. When local excesses of blood accumulated in the veins, the overbur- dened vessels were damaged and blood spilled over from the veins into the arteries. When this occurred, the ﬂow of pneuma, or vital spirit, which was supposed to be distributed by the arteries, would be obstructed. Given this theoretical framework, the logical objective of therapy was to diminish the plethora of blood. One way to accomplish this was to interrupt the production of blood at its point of origin by eliminating the supply of food. In addition to emetics, diuretics, mas- sage, hot baths, and general starvation, Erasistratus ingeniously induced a form of ‘‘local starvation’’ by tying tight bandages around the limbs to trap blood in the extremities until the diseased part of the body had used up its plethora. The use of the ligature to stop the ﬂow of blood from torn vessels was also ascribed to Erasistratus.
Although Erasistratus was sometimes called a materialist, atomist, or rationalist, he did not reject the concept of animating spirits. Appar- ently he believed that life processes were dependent on blood and pneuma, which was constantly replenished by respiration. Two kinds of pneuma were found in the body: the vital pneuma was carried in the arteries and regulated vegetative processes. Some of the vital pneuma got to the brain and was changed into animal spirits. Animal spirits were responsible for movement and sensation and were carried by the nerves, a system of hollow tubes. When animal spirits rushed into mus- cles, they caused distension that resulted in shortening of the muscle and thus movement. Perhaps inspired by the experimental approach of Strato (one of Aristotle’s favorite students), Erasistratus is said to have attempted to provide quantitative solutions for physiological problems. In one experiment, Erasistratus put a bird into a pot and kept a record of the weight of the bird and its excrement. He found a progressive weight loss between feedings, which led him to conclude that some invisible emanation was lost by vital processes.
A story concerning Erasistratus as a medical practitioner demon-strates his powers of observation and insight into the relationship between afﬂictions of mind and body. When Seleucus, one of Alexander’s generals, married a woman named Stratonice, his son Antiochus fell in love with his stepmother. Desperately trying to hide his feelings, the young man fell ill and seemed close to death. Many physicians had failed to help him when Erasistratus determined that an afﬂiction of the mind had weakened the body through sympathetic relationships. While carefully assessing his patient’s physiological reactions to the people who visited him, Erasistratus discovered the stammering, blushing, pal- pitations, and pallor that followed each visit by Stratonice. Erasistratus reasoned that although we can consciously conceal our thoughts, their inﬂuence on the body cannot be controlled. This story was retold many times for its literary merit, but the medical insights were largely ignored. Similar incidents appear in the biographies of other great physicians, including Galen and Avicenna, and were often cited in the extensive medieval and Renaissance literature concerning love-sickness.
For two hundred years, the museum of Alexandria supported a high level of creativity in science, technology, and medicine, and trained numerous physicians, engineers, geographers, astronomers, and mathe- maticians. Although it is difﬁcult to assess the vitality of such a complex institution, there is some evidence that medical science was already slip- ping into a state of decline during the time of Herophilus and Erasistratus. The tension that always exists in medicine between disinterested scien- tiﬁc research and the immediate needs of the sick grew and disrupted the ancient search for harmony and balance between the scientist and the healer. Critics of anatomical research charged that such pursuits distracted physicians from caring for patients. Much of the deterioration of scientiﬁc research at Alexandria can be blamed on the tumultuous political climate, but scientists and scholars seem to have been under- mining the structural supports of their own houses of learning by attack- ing rival schools of thought, or by leaving Alexandria to established new schools elsewhere. Later writers satirized the museum as a place where large numbers of scholars were kept like birds in a henhouse, end- lessly squawking and bickering. Finally, the worst of fates fell upon the Alexandrian scientists; they were persecuted, their grants were cut off, and they had to turn to teaching to eke out a living in new places.
The decline of the Alexandrian tradition was not limited to medi- cal science. Little of the work of the museum or library has survived. The ﬁrst major episode in the destruction of the library occurred in 48 B.C.E. during the riots sparked by the arrival of Julius Caesar and some three thousand legionnaires. After Caesar conquered Egypt, Alexandria was reduced to the status of a provincial town in the great Roman Empire. Later, Christian leaders encouraged the destruction of the Temple of Muses and other pagan institutions. According to tra- dition, in 395, the last scholar at the museum, a female philosopher and mathematician named Hypatia, was dragged out of the museum by Christian mobs and beaten to death. The Muslim conquest of the city in the seventh century (642–646) resulted in the ﬁnal destruction of the library and the loss of its precious manuscripts.