Short communication Fight-or-flight Response in the ancient Egyptian novel "Sinuhe" (c. 1800 BCE) Francesco M. Galassi ⁎, Thomas Böni, Frank J. Rühli, Michael E. Habicht Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland article info Article history: Received 24 November 2015 Received in revised form 12 January 2016 Accepted 9 February 2016 Available online xxxx Keywords: Fight-or-flight response Neurology Sinuhe Ancient Egypt Physiology The fight-or-flight response, described for the first time by Walter Bradford Cannon (1871–1945), is a physiological reaction that occurs in response to a harmful event or threat. It consists of autonomic-driven physiological changes such as acceleration of cardiac and respiratory rates, release of stored energy, dilation and more blood supply to muscles, mydriasis and so forth (Cannon, 1927). Before Cannon's description, the father of evolutionary biology, Charles R. Darwin (1809–1882), touched upon such physiological changes in his work “The Expression of the Emotions in Man and Ani- mals” (Darwin, 1872). Nonetheless, although science had to wait until such relatively recent times for a rigorous characterization of this phe- nomenon, reassessment of ancient literary sources, namely Dante Alighieri's (1265–1321) Inferno, has allowed researchers to hypothesize that a working understanding of the fight-or-flight response had al- ready existed for a long time (Galassi et al., 2016). Going further back in time, ancient Egyptian literature may well pro- vide an even more ancient example of this kind. Sinuhe, originating from the Middle Kingdom (c. 12th Dynasty, ca. 1800 BCE) is the first known adventure novel in recorded history describing the adventures of the state official Sinuhe in foreign lands after escaping a court conspiracy (Koch, 1990). From its publication the story met with large success, ul- timately leading to modern adaptations such as the novel Sinuhe (1945) by Mika Waltari (1908–1979), the Hollywood colossal “The Egyptian” (1954) by Michael Curtiz (1886–1962), or the denomination “Sinuhe” given to asteroid 4512 by the Finnish astronomer Yrjö Väisälä (1891– 1971) in 1939. The original Egyptian text harbours a medically intriguing sentence (Koch, 1990): “Confused by fear was my heart, both my arms extended, a shaking was falling on all my limbs. I run away jumping to search for me a place of hiding”- the verb ‘pskh’ clearly indicating “confused by fear” (Hannig, 2009). Analysing all these hints in the text, it appears that the fearful occurrence produces: • confusion, a state of emotional lability and unrest most likely caused by increased heart and respiratory rates; • increased blood supply to striate muscles of the limbs, which could be involved in fight or flight; • shaking; • hurried running and jumping. Although the description does not offer further details, here we have identified four clinical characteristics described by an adventurer from ancient Egypt about 4000 years ago. In conclusion, vague and removed from current physiological terminology as it may appear to be, yet this description very closely approaches our modern understanding of the fight-or-flight re- sponse, since it correctly highlights its most striking autonomic- induced cardiovascular and neurological changes. On account of this, this literary passage may well add to ante-litteram recorded cases of the response described by Cannon and show how even ancient Egyptians had somehow attained a good understanding of this fundamental biological process. Conflict of interest The authors declare that they have no conflict of interest. Ethical approval: This letter does not contain any studies with human participants or animals performed by any of the authors. Informed consent: No informed consent required for this study. Acknowledgements The authors wish to thank Mäxi Foundation and Cogito Foundations for financially supporting this review. Autonomic Neuroscience: Basic and Clinical xxx (2016) xxx–xxx ⁎ Corresponding author. E-mail address: francesco.galassi@iem.uzh.ch (F.M. Galassi). AUTNEU-01820; No of Pages 2 http://dx.doi.org/10.1016/j.autneu.2016.02.006 1566-0702/© 2016 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Autonomic Neuroscience: Basic and Clinical journal homepage: www.elsevier.com/locate/autneu Please cite this article as: Galassi, F.M., et al., Fight-or-flight Response in the ancient Egyptian novel "Sinuhe" (c. 1800 BCE), Auton. Neurosci. (2016), http://dx.doi.org/10.1016/j.autneu.2016.02.006