Ancient Greek medicine, influenced by other, receding civilizations, attributed healing powers to gods, such as Apollo and his son, Asclepius (1,2). In ancient medical centres founded around temples to Asclepius, known as ‘Asclepeiia’, priests applied ‘treatments’ based on divine faith and the placebo phenomenon. Subsequently, Ancient Greek medicine, ‘liberated’ from religious influences, was based on evidence and logical thinking (3). It advanced knowledge of physiology, pathophysiology, nosology and rational therapy and was largely attributed to the works and influence of Hippocrates and his school (1,2).

Hippocratic thinking and work were greatly influenced by pre-Socratic philosophers, predominantly including Pythagoras, Alcmaeon, Εmpedocles and Democritus (1,2). As a result, the Hippocratic doctrine established the clinical images and fixed time periods for the resolution of various diseases (2). Plato and Aristotle combined the significance of number ‘four’ with the doctrine of the ‘four elements, which corresponded to the qualities ‘dry’, ‘cold’, ‘hot’ and ‘moist’, according to the schematic diagram presented in Fig. 1 (2). The four elements ‘fire’, ‘air’, ‘earth’ and ‘water’ were rearranged into their qualitative components. These elements corresponded to the four humours of the body: ‘Blood’, ‘phlegm’, ‘yellow bile’ and ‘black bile’. These elements were combined to create a complex human personality system (1,2,4). The doctrine of the four humours, further developed by Galen, and Arabian and Persian physicians, influenced the understanding of diseases and the actions of drugs. Remedies and compounds were classified numerically based on their degrees of quality. For example, sugar was classified as cold, warm, dry and moist, while cardamoms were warm, cold and dry (2).

The system of the four humours somehow foreshadowed the endocrine and biochemical aspects of human physiology and pathophysiology (2). It could also be further claimed that this system encompasses an understanding of the homeostatic mechanisms of life. Ancient Greek natural philosophers, beginning with Pythagoras, initially described the concept of a ‘steady state’ of the body and soul with the words ‘harmonious balance’ and ‘isonomia’. Later, Epicurus referred to ‘eustatheia’ (eustasis) to express this fundamental concept. Homeostasis, which is derived from the Greek language, meaning ‘steady state’, was coined in 1930 by Walter Cannon to redefine this key concept at the beginning of the 20th century (5,6).

Galen, an ancient Greek physician, observed that women with ‘melancholic natures’ had a higher incidence of tumours of the reproductive organs. This observation led to the establishment of a connection between psychological stressors and the development of cancer dating back to the second century CE (7). ‘Melancholia’, as a term, describes an imbalance caused by excess of black bile (melaina chole) based on the Hippocratic theory of the humours (1,4,8,9). Hippocrates' humoural theory of the pathology of diseases further affected medicine in various ways throughout the medieval period, including Byzantine and Arabic, until the Renaissance and beyond (10).

There are three possible outcomes that may occur as a consequence of the interplay between stressors that distrupt homeostasis and adaptive responses that are triggered by stressors and re-establish it: An ideal match, which causes the organism to return to its basal homeostasis, also known as ‘eustasis’, an insufficient match, which leads to ‘dyshomeostasis’ or ‘cacostasis’, or a perfect match, which leads to a new improved equilibrium, also known as ‘hyperstasis’, are the three types of matches that may occur when encountering a stressor (5,11,12).

Currently, in the era of modern medicine, when the understanding of biology has grown immensely and technology has provided monumental study tools, an analogy could be performed between the ancient Hippocratic theory of the four humours and the regulatory psycho-neuro-endo-immune supersystem that deals with stress and comprises a huge nexus reflecting the above imbalances (Fig. 1) (11,13-17). Ancient wisdom teaches that to treat the disease of a patient, one should take a holistic approach, considering medicine as both an art and a science. Medicine requires an ethical, humanistic approach, strong compassion, robust factual knowledge, highly interpretive capacities to translate scientific biomedical knowledge, focus into specific health problems and exquisite judgement (18).

Other key messages from revisiting the thoughts of Ancient Greek Physicians and Philosophers indicate that they were able to successfully and respectfully integrate medical knowledge from other civilizations, for instance Egyptian traditions that potentially preceded the theory of humours of Hippocrates (19), the abandoning of theocratic medicine and other philosophical speculations influenced modern Evidence-Based Medicine, emphasizing thorough history-taking, holistic concepts and understanding human nature rather than speculating (4).

In conclusion, in the era of the hyper-specialized precision medicine and the hyper-compartmentalized science, an integrated re-thinking of biomedical science and a renewed approach to treating the patient rather than the disease, can draw examples from the Hippocratic tradition.