Annals of Internal Medicine History of Medicine Whither Prometheus’ Liver? Greek Myth and the Science of Regeneration Carl Power, PhD, and John E.J. Rasko, MBBS, PhD Stem-cell biologists and those involved in regenerative medicine are surgery, the beginnings of anatomical research, and the ancient art fascinated by the story of Prometheus, the Greek god whose im- of liver augury. In addition, the authors consider how the Greeks mortal liver was feasted on day after day by Zeus’ eagle. This myth understood Prometheus’ immortal liver. Not only do the authors invariably provokes the question: Did the ancient Greeks know examine the general theme of regeneration in Greek mythology, about the liver’s amazing capacity for self-repair? The authors ad- they survey several scholarly interpretations of Prometheus’ torture. dress this question by exploring the origins of Greek myth and medicine, adopting a 2-fold strategy. First, the authors consider what opportunities the ancient Greeks had to learn about the liver’s Ann Intern Med. 2008;149:421-426. www.annals.org structure and function. This involves a discussion of early battlefield For author affiliations, see end of text. holy grail of modern stem-cell research is the recre- liver regeneration. We then turn to the story of Aation of a functioning organ. The vital importance of Prometheus itself, placing it in the context of other Greek achieving this goal is all too clear. In the United States myths. After examining the general theme of regeneration alone, almost 9% of patients with liver failure die waiting in Greek mythology, we survey several plausible interpre- for a new organ. This is just 1 instance of a much broader tations of Prometheus’ unique torture. problem. With demand for transplantable organs far ex- ceeding supply, the need for regeneration therapies has FROM AUGURY TO ANATOMY never been greater. Like most Greek myths, that of Prometheus has ob- The story that has, above all others, captured the scure beginnings. The earliest literary account of imagination of those involved in regeneration research is Prometheus’ torture comes from Hesiod’s poem, The the Greek myth of Prometheus. Countless lectures and Theogony (eighth century BC), but the oral traditions on articles about regenerative medicine begin with a reference which Hesiod drew have uncertain origins (10). Because to this myth before turning to more scientific matters. Greek is an Indo-European language, one might expect Prometheus was the trickster god who tried to outwit Zeus that the Prometheus myth sprang from this linguistic fam- by stealing fire for mankind and, as punishment, was ily, but in fact its ancestors seem to have come from the chained to a crag in the Caucasus Mountains. Each day, an Near East. There are, for instance, close parallels between eagle would feast on his liver, and each night, his liver the myth of Prometheus and the Mesopotamian legend of would regrow in time for the eagle’s return (Figure 1). Enki (11, 12). The most plausible explanation is that the When hearing this tale, we cannot help but wonder if the mythical traditions of the Near East were transmitted to ancient Greeks had witnessed the amazing capacity of the Greece along trade routes either during the Late Bronze liver to restore itself. Although this possibility fascinates Age (1550 to 1200 BC) or during the period of renewed those engaged in regeneration research, they have not in- contact with the Near East that has become known as the vestigated the matter in any depth. Either they simply as- “orientalizing century” (750 to 650 BC)—the century in sume that the Greeks knew about the liver’s regenerative which Hesiod and Homer lived (13). powers (1–4), or they adopt an agnostic attitude (5–8). The influence of the Near East can be seen in the Chen and Chen (9) are exceptions, arguing that the mythology of the Greeks as well as in their magical and very logic of the Prometheus myth presupposes knowledge medical practices. For instance, hepatoscopy was an East- of liver regeneration. In their view, the Greek mythmakers ern import. Archaeologic evidence suggests that the prac- needed a punishment for Prometheus that was brutal with- tice of liver augury spread west from Mesopotamia to out being fatal—one that the god could endure for a pro- Greece and Etruria (14). The famous bronze liver (circa longed period without sustaining permanent injury. Their solution: repeated attack on an organ known to be capable of self-repair. They offer 2 suggestions about how the Greeks could have acquired this knowledge. One concerns See also: hepatoscopy, the art of reading animal livers to divine the Print will of the gods. Another concerns the knowledge that Key Summary Points .......................422 Greek healers might have gained by treating liver ailments. Although this case seems plausible prima facie, we think it Web-Only is necessary to take a much closer look at the evidence. We Conversion of graphics into slides examine how the Greeks may have glimpsed the truth of © 2008 American College of Physicians 421 Downloaded From: http://annals.org/ by a Kaohsiung Medica University User on 09/24/2015 History of Medicine Greek Myth and the Science of Regeneration or color of the liver would be understood not as an effect of Key Summary Points past natural causes (for example, the sheep having previ- Many cite the myth of Prometheus as proof that the an- ously suffered and survived some injury to its liver), but as cient Greeks were familiar with liver regeneration, knowl- a sign of what the gods plan for the future. For this reason, edge that was lost for thousands of years. we very much doubt that a Greek seer would have been able to recognize the evidence of liver regeneration even if The ancient art of hepatoscopy may have taught the it were right before his eyes. Greeks much about the superficial structure of animal liv- If it is doubtful that hepatoscopy revealed the truth of ers, but it would not have revealed the livers’ function and liver regeneration, what about Greek medicine? The poets regenerative capacity. provide the earliest and best literary source of evidence on this topic. Particularly valuable is Homer’s Trojan War As Homer’s work attests, early Greek medicine yielded epic, the Iliad, in which he describes war wounds in strik- very limited knowledge of human anatomy. Healers were ing detail. Here we find a handful of liver injuries—all unable to undertake major surgery and were prohibited fatal. For instance, Tros is sliced open by Achilles and his from doing autopsies. liver tumbles out in a gush of black blood (16). Although An advanced knowledge of anatomy and physiology was some have imagined that Homer possessed the knowledge needed to reveal the fact of liver regeneration, which is of a skilled anatomist (17), a less extravagant view now why this discovery belongs to 19th-century scientists. prevails among medical historians (18–20). Homer and his contemporaries had a very limited knowledge of human Because the Greeks regarded their gods as immortal, their anatomy. They could identify and name the main bodily mythology abounds in tales of supernatural vitality. This organs, and they knew well enough how to injure them, fact makes it unlikely that the Prometheus myth expresses but little more. Their knowledge came from the battlefield, a special knowledge of liver regeneration. sacrificial altar, and kitchen, not the dissecting table. In fact, apart from those relatively rare occasions when the There are many explanations of why the Greek mythmak- Greeks broke their own code of conduct and desecrated the ers targeted Prometheus’ liver for terrible and repeated bodies of their enemies, they did not cut open cadavers. abuse. The best explanations do not depend on the idea Religious scruples, veneration for the dead, and an abiding that the Greeks actually knew about the liver’s regenera- horror of corpses formed a powerful taboo against human tive capacity. dissection (21). That is why, long after the Homeric era, one of the Greek pioneers of anatomy, Aristotle (384 to 322 BC), had to admit that “the inner parts...areforthe most part unknown—at least those of man are, and hence third century BC) discovered near Piacenza, Italy, bears a we have to...[examine] those of other animals, the nat- remarkable resemblance to more ancient clay livers (circa ural structure of whose parts those of man resemble” (22). 1900 BC) (Figure 2) of Mesopotamian origin. These mod- It was not until the third century BC that Greek physicians els of sheep livers were designed to help seers practice and living in the frontier colony of Alexandria dared to dissect teach their craft. Although similar liver models have not humans. Members of the Alexandrian school, such as actually been found in Greece, it is clear from their litera- Herophilus and Erasistratus, were less constrained by the ture and iconography that the early Greeks regarded hep- Greek taboos against interfering with the dead. Moreover, atoscopy as an important form of divination. their passion for anatomical research was encouraged by an It has been said that the study of anatomy began with Egyptian king who supplied them with bodies, including the careful and repeated inspection of livers for divinatory perhaps the living bodies of convicts. Not surprisingly, the purposes (15). Could hepatoscopy have taught the Greeks study of anatomy took a great leap forward, and we owe about the liver’s marvelous capacity for regeneration? In the first detailed description of the human liver to the absence of real evidence, we must rely on educated Herophilus. Its accuracy is in sharp contrast to those that guesses.