Endocrine disruptors in ancient times and Greek mythology: the spring of Salmacis and the curse of Hermaphroditus

Abstract

According to Greek mythology, the spring waters of Salmacis (or Salmakis) feminized the god Hermaphroditus (or Hermaphroditos) and transformed his nature from male to half-male and half-female. The mythical properties of these waters are described in the writings of authors and philosophers of the Hellenistic period. It is evident that the spring of Salmacis and lake actually existed (located in Halicarnassus, today Bodrum, Turkey) and are not the product of poetic imagination. Hence, it could be hypothesized that there were certain natural elements in the waters that had a feminizing effect on the male reproductive axis. We now know, in fact, that naturally occurring environmental agents, also known as endocrine disruptors, can affect the endocrine and reproductive function of both males and females. However, since most endocrine disruptors today are manmade products of the modern industrial lifestyle, the presence and effect of naturally occurring disruptors in times preceding the Industrial Revolution are not widely discussed. It is thus against this background that we seek to formulate a differential diagnosis of male feminization attributable to the effect of natural environmental factors in the form of endocrine disruptors that will have existed in environments round the globe since time immemorial. We conclude that if there had been an accumulation of the mycotoxin zearalenone (ZEA) in the waters of Salmacis, chronic exposure to the lake’s water could have resulted in the phenotypic changes described in the Salmacis myth.

The myth of Hermaphroditus and the spring waters of Salmacis

In Greek mythology, Hermaphroditus scaled the heights of immortality’s hall of fame through the work of Ovid (Pūblius Ovidius Nāsō; 20 March 43 BC–17/18 AD), a Roman poet who lived during the reign of Augustus in the 1st century BC. Ovid is today best known for the Metamorphoses, a work comprising 15 books of continuous mythological narrative written in the meter of epic poetry, with the myth of Hermaphroditus being recounted in Book 4, as follows [1]. Hermaphroditus was the male child of Aphrodite and Hermes and was nursed by naiads of Mount Ida, a sacred mountain in Phrygia. He grew into a young man of extraordinary beauty and, keen to wander in unknown lands, traveled far from his home. During his journey in Asia Minor, he reached the area of Caria in Halicarnassus (today Bodrum, Turkey). In Caria, he chanced upon the nymph Salmacis (Greek: Σαλμακίς) bathing in her spring. Salmacis was overcome by lust for the young man and fell in love with him immediately. She tried to seduce him but was rejected. Thinking that she had left, Hermaphroditus undressed and entered the waters of the lake. However, Salmacis saw the young man swimming naked in her spring and leapt out from behind a tree and sprang into the waters. She wrapped herself around him, forcibly kissing him, and called out to the gods that they should never part. Her wish was granted: their bodies blended into one, forming “a creature of both sexes” [2]. Hermaphroditus lost his male nature and gained a new one, half-male and half-female, becoming the immortal symbol of the merging of the two human natures, male and female, into a single one (Fig. 1).

Fig. 1.

The nymph Salmacis and Hermaphroditus. Francois-Joseph Navez (1829)

According to the myth, when Hermaphroditus realized his absolute inability to resist his new nature, he called out his immortal parents. Ovid’s writings relate:

When he saw now that the clear waters which he had penetrated as a man had made him a creature of both sexes, and his limbs had been softened there, Hermaphroditus, stretching out his hands, said, but not in a man’s voice, “Father and mother, grant this gift to your son, who bears both your names: whoever comes to these fountains as a man, let him leave them half a man, and weaken suddenly at the touch of these waters!” Both his parents moved by this granted the prayer of their twin-formed son and contaminated the pool with a damaging drug. [2]

It has been established that the lake of Salmacis was not an imaginary mythological pool but an actual, topographically identified body of water that existed during Ovid’s time, with a spring within the walls of Halicarnassus. Ovid himself, when traveling together with Gnaeus Pompeius Magnus to Athens and around Greece, Asia Minor, and Sicily, described the pool in detail as a lake with crystal clear waters [2]. However, the myth concerning the peculiar waters of this lake was not Ovid’s poetic invention but was also described by other contemporary writers, such as the Greek geographer and philosopher Strabo and the Roman architect Vitruvius. Based on their testimonies, during the Roman imperial period, a small pool named Salmacis existed within the walls of Halicarnassus, in close proximity to the Mausoleum of Halicarnassus, the tomb of Mausolus, which was considered to be one of the seven wonders of the ancient world. However, “thus passes the glory of the world” (sic transit Gloria mundi), and after the Hellenistic period, the glory of Halicarnassus started to fade. The famous ruins of the Mausoleum were used by the Knights of St John of Rhodes to build the Castle of St. Peter, now known as Bodrum Castle, as the ancient pagan monuments were considered to be dangerous for followers of the Christian faith; meanwhile, the waters of Salmacis dried up, remaining alive and inspiring only poets of the Romantic era of European art.

In 1995, a group of Danish archeologists discovered the so-called “Salmacis Inscription” on the promontory of Kaplan Kalesi, which juts out into the sea to the south-west of Bodrum harbor. The inscription is a poem of the Hellenistic period, 60 lines long, written in elegiac verse and containing a list of famous authors born in Halicarnassus, including the historian Herodotus. The first lines form the poet’s invocation of the goddess Aphrodite. Early in Aphrodite’s story we encounter the water nymph Salmacis and her son Hermaphroditus. The inscription includes the following verse:

Having settled the lovely promontory sung of as dear to the immortals by the sweet stream of Salmakis, she (Halikarnassos) controls the beautiful dwelling of the nymph who once received our boy, Hermaphroditos, in her kindly arms and bred him to become an extraordinary man, who invented matrimony for mankind and was the first to fasten the matrimonial bed by law. She in her turn under the sacred streams dripping in the cave tempers the savage minds of men [3]

The ancient building where the inscription was discovered was most likely part of the temples of Hermes and Aphrodite, as described by the Roman architect Vitruvius. Indeed, in Halicarnassus, as well as in neighboring Pergamon, during Hellenistic times, Hermaphroditus was worshipped as a god of marriage. In the room next to that in which the inscription was found there is a side door that leads to a cave, most probably where the spring of the naiad Salmacis was located [3]. The fact is that since ancient times, the myth of a lake and its feminizing waters has been a topic of discussion among many writers and philosophers. Is it possible that these waters could have had such a supernatural effect?

Strabo, the Greek geographer and philosopher writes:

…the slanderous repute, for what reason I do not know, of making effeminate all who drink from it. It seems that the effeminacy of man is laid to the charge of the air or of the water; yet it is not these, but rather riches and wanton living that are the cause of effeminacy. [4]

Strabo visited Halicarnassus during the 1st century BC, a time when the city was prosperous and vibrant. As a true scientist, he could not accept that the self-indulgence and effeminacy of the people of Halicarnassus might be due to the “magical” effect of the air or the water; instead, he attributed the myth to the luxurious lifestyle of Halicarnassus people. This view was also supported by Vitruvius, who lived around the same time as Strabo and who, similarly to Ovid, describes the waters of the spring as clear. However, he states that “there is a mistaken idea that this spring infects those who drink of it… it cannot be that the water makes men effeminate” [5].

One would argue that the myth refers to an age much earlier than the time of Strabo, at the beginning of the Hellenistic era, when the population of Caria not only had no luxurious lifestyle but led a way of life that was to a large extent piratical. According to Vitruvius, when the first Greeks colonized the area of Halicarnassus, they restricted the native population to the hill of Kaplan Kalesi, where the lake of Salmacis was located [6, 7]. This is where the native population first interacted with the Greek colonizers, leading to the transformation of their everyday lifestyle to one resembling the elegant Hellenistic way of life. The latter transformation is also symbolically reflected in the myth of the feminizing waters of the Salmacis spring [5].

Since myths develop over time, one could speculate that certain shamanistic knowledge may have circulated regarding the existence of “magical” waters that were able to feminize males, which could have served as the basis of the developing myth. Moving forward, given that the myth was adapted to and incorporated in the local traditions of the city of Halicarnassus, it could symbolically reflect the gradual adoption of the “softer” lifestyle of the Hellenistic period. This could also account for the Salmacis inscription including the notion that the waters of the spring were de-demonized and describing them in a positive way as the waters that fostered the stunningly handsome Hermaphroditus. Finally, for the local society, the eternal blending of the male and the female in the body of Hermaphroditus symbolized the legitimate union of man and woman through marriage. Similarly, during the wedding ceremony, the Greek Orthodox Church blesses the couples with the words of the Apostle Paul: “Therefore, shall a man leave his father and his mother, and shall cleave unto his wife: and they shall be one flesh” [8]. This quote is part of Apostle Paul’s letter to the first Christians of Ephesus, Ephesus being a city located between Halicarnassus and Pergamon, which were located in a region where the cultural worship of Hermaphroditus as the god of marriage was popular.

Given that myths may be inspired by true facts, it could be speculated that the myth of Salmacis might have been based to a certain extent in reality. Can environmental factors indeed interfere with endocrine hormonal secretion by inhibiting the action of androgens and stimulating that of estrogens, leading to male feminization? We now know that such agents exist, which are called endocrine disruptors. Could the waters of the spring of Salmacis have been contaminated by such disruptors?

Medical interpretation: the feminizing waters of the spring of Salmacis and the role of mycoestrogens

Endocrine disruptors

According to the myth, the spring waters of the lake of Salmacis were able to feminize males. Male feminization is linked to either decreased action of androgens (sex hormones of the male) or accentuated action of estrogen (sex hormones of the female) and can manifest as changes that affect the following: (1) physical appearance/secondary sexual characteristics (increased breast development, redistribution of body fat, decrease in muscle mass, skin changes, decrease in facial and body hair growth, and decrease of testicular volume); (2) sexual behavior (decreased libido and erectile dysfunction); and (3) reproductive function (impaired spermatogenesis and infertility).

Hence, for the spring’s waters to induce such changes, they should have been contaminated with factors having an estrogenic and/or anti-androgenic action. Such environmental factors that affect the production, secretion, action, and metabolism of endogenous hormones are called endocrine disruptors [9]. Endocrine disruptors with estrogenic action can be further categorized as follows: (i) synthetic chemicals that are widely used in current industry (such as food conservatives and plastics), (ii) pharmaceutical agents (medications for humans/animals and pesticides), (iii) heavy metals and industrial waste products (such as dioxins), and (iv) naturally occurring agents [9, 10]. The disruptors belonging to the first three categories are modern chemicals and did not, of course, exist in ancient times. Thus, the focus of the present report, which will attempt to solve the mystery of the spring of Salmacis, will be on naturally occurring estrogens.

Naturally occurring estrogens

Compounds with estrogenic action can be found in the environment and include phytoestrogens and mycoestrogens. Phytoestrogens are produced by plants and have a similar structure and/or action to that of estrogens, which are secreted by the human/animal ovaries and the placenta. Phytoestrogens may serve as a plant’s defense mechanism against various pathogens and animals and may also contribute to the plant’s color [11]. Phytoestrogens are broadly categorized into flavones, phytosterols, and lignanes, with many plants containing more than one type of phytoestrogen. They are detected at high concentrations in a variety of plants, predominantly in soy, but also in clover, plant-based oils (e.g., sesame oil and palm oil), sesame seeds, and flax seeds [11]. Other potential sources of phytoestrogens are algae, aquatic macrophytes that grow in lakes and rivers, and cyanobacteria, the first oxygen-producing organisms on Earth that frequently colonize lakes and spring waters. The estrogenic effect of phytoestrogens is 1,000 to 1,000,000 times weaker compared to that of estradiol, the major female sex hormone. Among phytoestrogens, the strongest effect is demonstrated by coumestrol, an isoflavone that is found in large amounts in Medicago sativa, also called lucerne, a plant of the clover family that has since ancient times been cultivated as an important forage crop in many countries around the world [11].

Mycoestrogens belong to the larger category of mycotoxins, agents that are the metabolic byproducts of several types of fungal organisms and can have an adverse impact on human health [12]. Among them, the most potent estrogenic endocrine disruptor is zearalenone (ZEA) and its metabolites. ZEA is produced by the Fusarium (mostly Fusarium graminearum) fungal species, which are hyphomycetes that are invisible to the naked eye, their size being in the micrometer range. Fungi of the genus Fusarium may infect grain during flowering, but they also contaminate stored plant materials and have been detected in the soil as well as in river and lake waters. ZEA is frequently observed in maize, but since fusarium spores are ubiquitous, it has also been found in barley, oat, wheat, rice, sorghum, and soybeans in both warm and moderate climate zones [13, 14]. While Fusarium is resistant to low temperatures (even below 5 °C), the ideal temperature for its development is 20–30°C: its growth accelerated when humidity reaches > 20%. Such species are common in regions with a temperate climate, including the countries of the Northern Hemisphere and, thus, their presence in antiquity in the East Mediterranean region, the cradle of Hellenic civilization, is certain [15]. In such climatic conditions, Fusarium’s ability to produce toxins maximizes; it mainly produces deoxyvalenole, which is toxic for the plants that the fungus colonizes, and ZEA, which can directly affect animals and even humans. It is noteworthy that coexistence of ZEA with other mycotoxins can boost their action. For example, alternariol is a mycotoxin with very weak estrogenic action that is produced by the microscopic fungus Alternaria alternata and affects several plants. When this toxin coexists with ZEA, the estrogenic effect of their combination increases significantly, matching the estrogenic effect of human estradiol [16].

Animals are usually exposed to ZEA through being fed contaminated feed and, since the toxin is not removed by regular food processing, humans can be exposed through consuming a large variety of products, such as cereal, wine, beer, and the meat and milk of affected animals. Furthermore, exposure to the toxin through potable water is also possible [17]. This toxin was in fact first detected in drinking water in Detroit, MI, USA, in 1996 [18]. ΖΕΑ is a nonsteroidal estrogenic mycotoxin which, due to its similarity to the molecule of estradiol, can bind to the estrogen receptor. The estrogenic action of ZEA and its metabolites is much stronger than that of phytoestrogen and, in some experiments, it is equivalent to that of estradiol [11]. More specifically, ZEA’s metabolite a-zearalenone (α-ZOL) has even stronger estrogenic action than ZEA itself. Apart from their ability to bind to the estrogen receptors, ZEA and its metabolites can affect the endocrine system through their structural similarity to sex steroids, by competing with them for the enzymes that catalyze the reactions of steroid hormone biosynthesis [19]. It has been shown that even very small amounts of ZEA and α-ZOL can significantly limit the production of testosterone in the testicles’ Leydig cells in mice [20]. Studies at the cellular level have shown that ZEA can restrict cell proliferation and growth in the ovaries and testes (apoptotic function) through the regulation of the cell cycle, cytoskeletal changes, DNA methylation, and oxidative stress [17].

The effect of ZEA has particularly been demonstrated in pigs, sheep, horses, and cows. When exposed to ZEA, female animals may suffer from vaginal prolapse, enlargement of the breast and uterus, pseudopregnancy, infertility, and teratogenic effects (exposure during pregnancy). On the other hand, affected male animals demonstrate significant breast enlargement, testicular atrophy, decrease in testosterone levels, decrease in aggressive behavior and libido, impaired spermatogenesis, and infertility [15, 20]. Moreover, in zebrafish, a species that is characterized by periodic hermaphroditism due to high sensitivity of their reproductive axis to hormones and hormone-mimetics, exposure to ZEA can affect the reproductive cycle, inducing female offspring production instead of male [21, 22].

Adverse effects of ZEA have also been described in humans. In women, ZEA can cause changes in the endometrium and suppresses the secretion of hormones that are important for their reproductive function, such as LH and progesterone. It can also have a toxic effect on embryonic stem cells, while exposure of pregnant women to ZEA is associated with increased risk of miscarriage, low birth weight, and reduction in milk production during lactation [15, 20, 23]. In men, ZEA negatively affects spermatogenesis and sperm survival, leading to oligospermia [15, 24]. Finally, high levels of ZEA have been detected in children with premature breast development and/or precocious puberty [15, 17, 20, 24].

Water contamination by naturally occurring estrogens

The most common route of human exposure to phytoestrogens and mycoestrogens is through the consumption of foods or supplements that contain these elements, either as ingredients (e.g., phytoestrogen in soy) or as contaminants (e.g., mycotoxins in cereal or even drinking water). How could such toxins come to be found in potable water? First, they could be transferred by rain or irrigation of crops, before finally ending up in a river or a lake. Another source could be storage spaces of plants that are located near surface or underground water. Finally, industrial facilities for animal breeding and food or waste processing can contaminate an area’s drinking water. Recent studies have reported that a large number of water ecosystems round the world have been contaminated with phytoestrogens and mycoestrogens [11, 13, 25]. Toxin levels can vary considerably and depend on numerous factors, including, inter alia, regional characteristics, the season of the year, and the water recycling rate of each ecosystem. In many cases, the concentration of these toxins exceeds the current safety limits [11, 13, 25, 26].

Based on all the above, we can now attempt to provide a theoretical scientific explanation for Hermaphroditus’ curse and the feminizing waters of the spring of Salmacis. According to Ovid’s description, the waters were crystal clear without any signs of aquatic plants, apart from surrounding grass. This allows us to reject the hypothesis of contamination of the lake by phytoestrogen deriving from algae, cyanobacteria, or aquatic plants. Judging from Ovid’s writings, the grass that surrounded the lake could have served as a possible source of phytoestrogen which might have contaminated its waters. It is now known that some kinds of grass (e.g., Lolium multiflorum) and clover (Medicago sativa) contain significant amounts of isoflavones and particularly coumestrol, which have been identified at high concentrations in rivers, especially close to plant crops [11, 26]. One of the most potent estrogens that nature produces is ZEA. Bearing in mind that ZEA is produced by a fungus affecting mostly cereals (it is of note that cereals comprised the main crop cultivated in Asia Minor in antiquity) and that the climatic conditions of the region are ideal for the development and production of its toxins, the hypothesis of contamination with ZEA of the lake of Salmacis is very possible. ZEA might have originated either from arable lands or from cereal storage spaces in close proximity to the lake and could have polluted it via rain or underground water channels. If the environmental conditions promoted the accumulation of ZEA and/or coumestrol in the lake’s water, then long exposure to it (e.g., due to chronic consumption of the spring’s water) could result in feminization of males.

Our attempt to provide a medical interpretation of the myth of the spring of Salmacis has obvious limitations. First, the case under review, namely, Hermaphroditus, is a mythical figure and information about his physical appearance stems from an epic poem and not an objective scientific description, while, needless to say, physical examination and blood testing for hormone levels cannot be performed for the same reason. Moreover, our hypothesis that contamination of the lake’s water with potent mycoestrogens or phytoestrogens could have led to feminization of males following long-term exposure to it cannot be tested as the lake no longer exists.

We are thus obliged to leave as yet unproven our scientific hypothesis of possible mycotoxin contamination of the spring’s/lake’s waters in ancient times and a resulting feminizing effect and remain with the poetical symbolism of the myth denoting, on the one hand, the mixing of the indigenous peoples of Asia Minor with the later Greeks who colonized the region and, on the other, the sacred union of man and woman via which they experience oneness through the merging of two.

Data availability

Not applicable.