The ancient Greek myth of Titan Prometheus and his punishment for deceiving Zeus and protecting mankind is known to most members of the scientific community who study hepatic diseases, mainly because Prometheus’ liver was the target of torture.
However, the myth of Prometheus is known and cherished by many, because, according to one version, Prometheus created the first man. The ancient poet Hesiod (8th century BC) records that Prometheus twice tricked the gods. First, he offered mortals the best meat from a slaughtered cow and gave the fat and bones to the gods. Then, when an infuriated Zeus punished man by taking fire, Prometheus stole it back for mankind. Accordingly, Zeus punished him in two ways. First, Prometheus was bound on the mountain Caucasus. More explicitly, for students of the liver, an eagle fed from his liver each day, but the liver regenerated overnight. Secondly, Zeus sent Pandora to the world where she released all hitherto unknown evils to humans.
While Prometheus is well recognised, less is known about another figure in legends who received the same punishment and whose myth could also be used by modern hepatologists as an ancient example of the phenomenon of liver regeneration. According to Greek mythology, Tityus (Τιτυός or Τιτύας in Greek), son of Zeus and Elara, was a gigantic chthonic being, living in Phocis and Euboea.
When Elara became pregnant by Zeus, he hid her deep in the earth so that his wife Hera would not learn of this. There Elara gave birth to Tityus, who was nursed by Gaia (goddess of earth) and grew to enormous proportions. Tityus was so large that his body was said to cover nine acres. In another version of the myth, Tityus was gigantic even as a fetus and, because he ruptured his mother’s womb, he had to be carried to term by Gaia herself; most likely making her the first surrogate mother in human ‘‘myth-history”. When Tityus grew up he made the mistake of assaulting goddess Leto, mother of Apollo, the god of light, and of Artemis, goddess of hunting. Specifically, when Leto was traveling from Panopeus in Phocis on her way to Delphi, Tityus attempted to rape her, possibly encouraged by Hera. Leto cried out to her children who immediately came to her rescue and tried to kill the giant with their arrows. Tityus, however, was immortal but could be punished by Zeus who had him bound in Hades, the ancient kingdom of the Dead, where two vultures were fed on his liver which, as in the Prometheus legend, regenerated perpetuating the torture eternally.
Homer refers twice to Tityus in the Odyssey. First, a hero called Rhadamanthys is said to stop in Euboea to pay him a visit (chapter 7) and then Odysseus, in his descent to Hades, describes how he saw Tityus being tortured (chapter 11): ‘‘I saw Tityus too, son of the mighty Goddess Earth—sprawling there on the ground, spread over nine acres—two vultures hunched on either side of him, digging into his liver, beaking deep in the bloodsac, and he with his frantic hands could never beat them off, for he had once dragged off the famous consort of Zeus in all her glory, Leto, threading her way toward Pytho’s ridge over the lovely dancingrings of Panopeus”. Tityus and his myth are also referred to by many other ancient poets and writers like Pindar, Apollonius Rhodius, Strabo, Pausanias, Ovid, and Virgil.
In the Prometheus myth, the liver was chosen as the focus of torture because the ancient Greeks regarded the liver as the seat of life, soul, and intelligence. The indestructibility of the soul is, in this way, connected to the regenerative capacity of the liver, referred to as ‘‘immortal” by Hesiod. Furthermore, by choosing the liver, the punishment of Prometheus becomes even more heinous since, because of the capacity of the liver to regenerate, the suffering of the hero is perpetuated. Similarly, the liver is also chosen as the site of punishment of Tityus. His liver is referred to as ‘‘inexhaustible” and ‘‘always-replenishing” by the Roman poet Virgil in his epic ‘‘Aeneid” and ‘‘constantly growing afresh” by the Roman dramatist and philosopher Seneca in ‘‘Phaedra”.
In the Tityus myth the vultures come to devour the giant’s liver every new moon. In contrast, Aeschylus says that the eagle came every other day to feed on Prometheus’ liver, whereas Hesiod comments that the ‘‘long-winged” bird came every day. These versions of hepatic regenerative capacity indicate a time-span for the liver’s reparative activity from one night to 28 days. Irrespective of the mythic time-frame of liver regeneration, both legends raise the possibility that ancient Greeks may have had some knowledge not only of the organ’s potential for repair but also of the quantitative and temporal aspects of liver regeneration. Nevertheless, the concept of liver regeneration was introduced in modern medicine in the early nineteenth century. Different possible explanations exist as to how the understanding of liver regeneration may have come about more than two and a half millennia ago. It may be that the ancients observed the growth of animal livers as a part of the practice of liver divination, using the liver to predict the future. Alternatively there may have been opportunities to study liver healing after superficial liver wounds following battle or by observation of healing after draining liver abscesses.
The myths of Tityus and Prometheus reveal only one aspect of liver regeneration, namely the organ’s ability to reconstitute its mass after partial removal. Twenty-seven centuries passed before the first experimental model of liver regeneration following partial hepatectomy, the pioneering work of Higgins and Anderson was published in 1931.
The concepts of ancient mythographers were confirmed in observations that showed that liver mass increases a few hours after partial hepatectomy and, at least in rats, reaches normal size by 72 h. The increasing utilization of live donor and splitliver transplantation has triggered the need to better understand the mechanisms that regulate and promote liver regeneration. Many studies have shed light on the molecular basis of liver regeneration.
Full comprehension of the phenomenon of liver regeneration awaits increased understanding of the pivotal role of the liver in the regulation of body homeostasis and in its complex interactions with other tissues and organs.
(Source: “Tityus: A forgotten myth of liver regeneration” Dina G. Tiniakos et al.)
Research-Selection for NovoScriptorium: Maximus E. Niles