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Born in Frauenheld, East Switzerland, on March 17, 1881, I, Walter Rudolph Hess, grew up with a father who taught physics. My father taught me the basics of dealing with apparatus and how to be careful in these spaces. Another building block of my life came from my adventures in nature and trying to understand and observe many parts of it in my own ways. While physiology caught my eye from the start, I started out in ophthalmology and as a surgeon after I graduated from Medical School in which I learned a great deal in precise behaviors and practices in medicine.
My love for physiology eventually got the best of me and while I was thriving in ophthalmology, I became an assistant in order to pursue my passion.

After being named the director of the Physiological Institute oat Zurich, serving in the First World War, and connecting with other physiologists, I worked my way into the regulation of respiration. This brought me to the diencephalon wherein I earned my Nobel Prize. This brought me up to when I eventually retired according to the regulations. While I sneaked in a few years of research after this with limited space and staff, I eventually passed away in the year of 1973.

Source: https://www.nobelprize.org/prizes/medicine/1949/hess/biographical/

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In 384-322 B.C.E, Aristotle approached the function of the hypothalamus without knowing what part of the brain it was at the time with the belief that the brain controlled basic human functions to maintain homeostasis. These functions consisted of regulating food intake and body temperature, considering the heat of the blood. He approached this idea of homeostasis in that in order for one system to do something, another system has to also react in order for the first system to do what it needs to do. This explains how the body is able to complete certain tasks and functions while staying in a state of integrity.  It would take quite some time after Aristotle to determine what part of the brain controlled these functions.

I am including this information and this artifact to show simply how old the ideas of Aristotle stem from as well as how smart Aristotle was for his time. He was able to apply his  understanding of the world to the human body and correctly predict the necessary mechanisms which now involve the hypothalamus.

Sources: Toni, R. Ancient Views on the Hypothalamic-Pituitary-Thyroid Axis: An Historical and Epistemological Perspective. Pituitary 3, 83–95 (2000). https://doi.org/10.1023/A:1009953723963

Shields, Christopher, "Aristotle", The Stanford Encyclopedia of Philosophy (Fall 2020 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/fall2020/entries/aristotle/>.

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During the times when the belief of the three ventricles was the main component of the powerhouse of the brain, the hypothalamus was discovered. It was the 2nd century AD when Galen of Pergamon first identified the hypothalamus and declared it as a passageway for mucus to pass from the third ventricle to the nasopharynx. He decided that the arteries around the pituitary gland carried the "the vital spirit" which was then transformed into "the animal spirit" or nerve impulses and were then distributed throughout the body. These ideas lived on to be considered by an anatomist in the 14th century known as Mondino de' Liuzzi and later by Andreas Vesalius.

Galen provided valuable information on the brain but was not able to correctly identify the ideas of the hypothalamus. It was hard for him to understand the complexity and the importance of different parts of the brain like the hypothalamus. And while it was also not his fault for the ideas sticking around for so long, it was simply hard to shake them after it had been so long even though they weren't very close to the real idea whatsoever.

Citations: Toni, R. Ancient Views on the Hypothalamic-Pituitary-Thyroid Axis: An Historical and Epistemological Perspective. Pituitary 3, 83–95 (2000). https://doi.org/10.1023/A:1009953723963

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Vesalius's drawing's of the infundibular-pituitary stalk

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While Mondino de' Liuzzi and Andreas Vesalius generally agreed with Galen's ideas, they also added some details of their own alongside a few other scientists. 1315 brought with it the first human dissection since Herophilus and Erasistratus and it was done by none other than Mondino de' Liuzzi himself.  In 1316 Mondino brought to fruition the third ventricle as the "integrator" of emotional, behavioral, and psychic responses which connects to the ideas of what the hypothalamus does as the regulator of the body. His work inspired later artists like Vesalius and Leonardo da Vinci. Vesalius supported Galen's ideas by bringing important drawings of the hypothalamus infundibulum to the forefront Leonardo da Vinci also drew some of the most in-depth drawings of the brain of this time period and through the Renaissance era.

Liuzzi was an important figure in connecting Aristotle's ideas of homeostasis with a general area of the brain. This allowed for further inspection thus bringing a more detailed understanding later on.

Sources: Lechan RM, Toni R. Functional Anatomy of the Hypothalamus and Pituitary. [Updated 2016 Nov 28]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279126/

Mavrodi, A., & Paraskevas, G. (2014). Mondino de Luzzi: a luminous figure in the darkness of the Middle Ages. Croatian medical journal, 55(1), 50–53. https://doi.org/10.3325/cmj.2014.55.50

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Berengario’s De fractura cranei (left), Berengarios’s Isagogae breves (right)

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There wasn't full support for Galen's ideas though when Berengario da Carpi, in 1522, denied the existence of Galen's ideas on rete mirabilis. This Galenic belief stated that the arterial structures in the area of the pituitary gland. Berengario started off studying at the University of Bologna in 1489 and quickly became a well-known physician and surgeon. As a professor, his most famous writing was his Commentaria where he challenged those Galenic ideas. He explored the meninges, cranial nerves, and the various parts of the ventricular system like the choroid plexus, interventricular foramen, infundibulum, and more. Despite Berengario's work though, the support for leaving behind Galen's ideas didn't come to fruition until the 1600s.

Sources: Parent A (2019) Berengario da Carpi and the Renaissance of Brain Anatomy. Front. Neuroanat. 13:11. doi: 10.3389/fnana.2019.00011

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The Break in the 16 Century Belief System

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The Break in the 16 Century Belief System

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While Berangario da Carpi did not agree with Galen's beliefs, they did not change much. Due to restricting circumstances where the brain could not be dissected for much of the next few hundred years and other factors, new ideas of the hypothalamus did not evolve until the 18th century. Some of these new ideas came from Luigi Galvani who disproved the idea that the hypothalamus acted as a passageway for mucous from the ventricles when he found that mucous actually comes from mucous glands in the nasal mucosa in 1767. Galen's ideas were also disproven on the other side of it when in 1787, Paolo Mascagni found that fluid in the brain drains with the lymphatic vessels in the meninges.

Sources: Lechan RM, Toni R. Functional Anatomy of the Hypothalamus and Pituitary. [Updated 2016 Nov 28]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279126/

https://blogs.cuit.columbia.edu/hslarch/tag/paolo-mascagni/

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The Beginning Details of the Hypothalamus

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The Beginning Details of the Hypothalamus

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1928 came with the tip of the iceberg with understanding how the hypothalamus works. Ernst and Bertha Scharrer found "glandular cells" in the hypothalamus of fish. This led to the idea of "neurosecretion". They tried to use morphology, the study of the structure of things, to support their ideas in neurosecretion. The Scharrers attempted to distinguish neurosecretion as a different process from other chemical signaling that is used throughout other neurons in the brain.

John Green and Geoffrey Harris played important roles in connecting the pituitary gland and hypothalamus. They dove into the structural components of the hypophyseal portal vasculature which is the collection of the blood originating from the hypothalamus which then is directed into the anterior pituitary gland.

https://www.britannica.com/science/hypothalamic-hypophyseal-portal-circulation

Watts A. G. (2015). 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris. The Journal of endocrinology, 226(2), T25–T39. https://doi.org/10.1530/JOE-15-0157

Lechan RM, Toni R. Functional Anatomy of the Hypothalamus and Pituitary. [Updated 2016 Nov 28]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279126/

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In 1925, Walter Rudolph Hess started in the autonomic nervous system, which integrates and controls the functions of organs that are automatic. He became interested in physiology and looked into the diencephalon. He worked with cats and dogs in which the hypothalamus was the source of this homeostatic mechanism through electrical stimulation. He would stimulate certain parts of the structure which would then lead to a variation in the animal's heart rate, respiratory rate, blood pressure, and fear. Rudolph found both areas of the hypothalamus that increased these stress-induced processes or increased the calming processes.

These findings had not been found before and led to a rapid increase in research on this area which is still being done. Walter Rudolph Hess earned his joint noble prize in 1949. This artifact was chosen due to him being known for stimulating the hypothalamus of a cat's brain and seeing them become drowsy or aggressive depending on where he stimulated it.

Sources: Shampo, M. A., Kyle, R. A., & Steensma, D. P. (2011). Walter Hess—Nobel Prize for work on the brain. Mayo Clinic proceedings, 86(10), E49. https://doi.org/10.4065/mcp.2011.0560

https://www.uzh.ch/cmsssl/en/about/portrait/nobelprize/hess.html

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The Details Hess Could Never Have Dreamed Of

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The Details Hess Could Never Have Dreamed Of

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The details that 2022 has brought in the research of the hypothalamus would have wowed even the great Walter Hess. Kazuhiro Nakamura and others looked into the extreme stressors like extreme temperatures and lack of food and the response it generates.  Thermoregulation, the regulation of body temperature, and cardiovascular responses are stimulated by inputs to the preoptic area of the hypothalamus which coordinates sleep and body temperature. Meanwhile, psychological stressors, which come from the ventromedial prefrontal cortical area, the area responsible for the basis of our personality and executive function, affect the dorsomedial hypothalamus. Another main stressor is starvation stress where medullary reticular neurons, neurons that govern the facial nerves, are activated in ways to promote the drive for chewing and therefore eating.

All of these details are layers beneath what Walter Hess originally found but could never have come to fruition without his discoveries to start it.

Source: Nakamura, K., Nakamura, Y. & Kataoka, N. A hypothalamomedullary network for physiological responses to environmental stresses. Nat Rev Neurosci 23, 35–52 (2022). https://doi.org/10.1038/s41583-021-00532-x

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Beginning in 1860 Von Luschka explained the hypothalamic capillary plexus of the portal vessels, being the arterial and veins that transport the blood from the hypothalamus to the pituitary gland. About 15 years later, Theodor Meyn, a German-Austrian psychiatrist, neuropathologist, and anatomist, and his trainee Auguste Forela Swiss Mymecologist, neuroanatomist, psychiatrist, and eugenecist, provided the anatomical borders which separate the hypothalamus from the other structures within the subthalamus. Shortly after, Swiss anatomist, Wilhelm His coined the term "hypothalamus", meaning "under, chamber" in Ancient Greek due to it being under the thalamus, in 1893.

Sources: Lechan RM, Toni R. Functional Anatomy of the Hypothalamus and Pituitary. [Updated 2016 Nov 28]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279126/