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Epiphaniae medicorum, uroscopy and ring of flasks (Diagnosing diabetes: a wee taste of honey)… “no essential part of the drink is absorbed by the body while great masses of the flesh are liquefied into urine.”- Aretaeus of Cappadocia[1]Although it seems to have gained notoriety only recently as increasing numbers of people across the globe have fallen prey to the disease, countless brilliant minds have played a part in the fascinating history of diabetes mellitus. Scientists and physicians have been chronicling this devastating medical condition for more than 3,000 years, from the origins of its discovery to the dramatic breakthroughs in its treatment. In antiquity, a diagnosis of diabetes was likely a death sentence.Cedar wood panel depicting Hesy-Ra (Hesy-Ra - Wikipedia)The first known mention of diabetes symptoms was in the Ebers Papyrus 1552 B.C., where Hesy-Ra a third dynasty physician (whose title was Wer-ibeh-senjw, meaning either "Great one of the ivory cutters" or "Great one of the dentists"), documented frequent urination as a symptom of a mysterious disease that also caused emaciation. Hesy-Ra mentions the “too great emptying of the urine'.The following mixture was prescribed for the treatment of polyuria (excessive urination): ‘A measuring glass filled with Water from the Bird pond, Elderberry, Fibres of the asit plant, Fresh Milk, Beer-Swill, Flower of the Cucumber, and Green Dates”.[2]It's unclear whether the condition described was excessive urine (polyuria), which may have been symptomatic of diabetes, or increased frequency of urine, resulting from a urinary tract infection[3] . Urinary troubles were corrected with rectal injections of olive oil, honey, sweet beer, sea salt, and seeds of the wonderfruit.[4]Egyptian medicine influenced the medical practices of neighboring cultures, including the culture of ancient Greece. Although the Greek physician Hippocrates, the father of medicine, did not specifically mention diabetes in his writings, there are accounts in the Hippocratic writings that are consistent with the signs and symptoms of diabetes.[5] There are references to excessive urinary flow with wasting of the body. Hippocrates promoted the concept of preventive medicine, stressimg the influence of diet, exercise, and lifestyle on health.[6](Origin of surgery Sushruta (Origin of surgery Sushruta - Fancy Frindle)The ancient Indian physician, Sushruta (6th century BC), and the surgeon Charaka (400–500 A.D.) were able to identify the two types, later to be named Type I and Type II diabetes.[7] Sushruta called diabetes the disease of madhu-meha, i.e., sweet urine.[8] The first clinical test of diabetes was devised in Ancient India, where patients exhibiting the common diabetes symptoms described above, had their urine analyzed with the help of ants.[9] If the sugar-loving ants came rushing to the urine, a diagnosis of “madhumeha” was given, indicating the patient had “honey urine”, with elevated levels of glucose in the urine.[10]Another ancient Ayurveda physician, Charaka, who lived in the 3rd century BCE called diabetes the disease of prameha, referring to abnormally high outputs of urine.[11] Both physicians advocated abstaining from sweet foods and reducing the intake of rice and other grains as part of the treatment of diabetes.[12]Apollonius of Memphis (A history of Diabetes timeline)There are two contenders for coining the term diabetes meaning to pass through. The first is Apollonius of Memphis, around 250 BC, while the second is Demetrius of Apamea (1st century BCE).[13] Apollonius of Memphis. is credited with naming the disorder for its top symptom: the excessive passing of urine through the body’s system.[14] Demetrius, likened polyuria to the siphoning of wine between pots—a practice now called "racking," which has long been used during fermentation to remove the sediment of dead yeast and promote proper aging.[15]Caelius Aurelianus prepared a Latin version of the works of Soranus, including in the index a subject heading for "Diabetes”. Caelius quotes Apollonius of Memphis as separating two forms of dropsy, one marked by retention of fluid and the other by the inability to retain fluid; the patient discharges whatever he drinks as if it were passed through a pipe. Caelius Aurelianus continues by stating that Demetrius distinguishes this disease from dropsy in which any fluid that is drunk is discharged as urine. Demetrius calls this condition diabetes.[16]Aulus (Aurelius) Cornelius Celsus, a Roman physician, was credited with the first recording of the cardinal signs of inflammation, which included calor (warmth), dolor (pain), tumor (swelling), and rubor (redness and hyperemia).[17] He describes a condition likely to be diabetes, calling it "excessive pouring out of urine" causing "emaciation and danger”.[18]In the first century A.D., ancient Greek physician Aretaeus vividly described the destructive nature of an illness which he named diabetes derived from the Greek word “siphon” (meaning flowing through).[19]Diabetes is … not very frequent ... being a melting down of the flesh and limbs into urine … for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. It consists in the flesh and bones running together into the urine … the illness develops very slowly. The nature of the disease is chronic, and it takes a long period to form; but the patient does not live long once the disease is fully established; for the melting is rapid, the death speedy. Moreover life is disgusting and painful; thirst, unquenchable … and one cannot stop them either from drinking or making water".[20]Diabetes indeed appears to have been a death sentence in the ancient era: Aretaeus did attempt to treat it, but could not provide a good prognosis. He commented that "life (with diabetes) is short, disgusting and painful”.[21] In 164 AD, building upon Aretaeus’ assessment, Greek physician, Galen of Pergamum, categorized diabetes as an ailment of the kidneys.[22]The Origins of Diabetes | St. Hope FoundationFor several hundred years, the treatises of Aretaeus and Galen remained the definitive reference for the diagnosis of diabetes, but offered no cures. To the east, Chinese physicians described the disease similarly, labeling it xiao ke (wasting and thirsting), a term still used today.[23] Xiaoke tea, a traditional Chinese treatment for diabetes mellitus was thought to lower blood glucose concentrations.[24]As the Middle Ages began, diabetes was known as the “pissing evil”[25] , commonly diagnosed by “water tasters”, who tasted the urine of people thought to have diabetes to see if the excretion was sweet like honey.[26] Avicenna (980–1037 A.D.), the great Persian physician, in The Canon of Medicine not only referred to abnormal appetite and the decline of sexual functions, but observed diabetic gangrene but also concocted a mixture of seeds (lupin, fenugreek, zedoary) as a panacea.[27]Thomas Willis in the late 1600s added the term mellitus or "from honey" to separate the condition from diabetes insipidus, which is also associated with frequent urination.[28] Willis was infamous for his diagnosis of diabetes, which involved tasting the urine of his patients.[29] He associated diabetes with depression (“diabetes is caused by melancholy”), an observation that was only rediscovered three centuries later.[30]With little understanding of pathophysiology, early remedies for diabetes included diverse and interesting prescriptions like “oil of roses, dates, raw quinces and gruel, jelly of viper’s flesh, broken red coral, sweet almonds and fresh flowers of blind nettles” representing a variety of beliefs and practices of the times.[31] The prescribed treatment was exercise, which is consistent with medical advice for today, but with one difference: the preferred method of exercise was horseback riding.[32] It was thought that this would decrease urination frequency.Later, in the pre-insulin era, calorie restriction reigned supreme, and graphic accounts of the terminal gasping and sighing and sweet smell (ketosis) surrounding the patient in a diabetic coma abound in the volumes written on the disease.[33]Research published in the journal ‘Nature’ reveals that the likelihood of non-African Homo sapiens developing conditions, particularly auto-immune disorders, which can be determined by Neanderthal alleles. DNA sequencing was conducted on a recent skeletal discovery from Denisova Cave, indicating that what were considered modern diseases originated in our Neanderthal ancestors.[34] The diseases included type two diabetes, Crohn's disease, lupus and biliary cirrhosis.[35]The deep roots of diabetesThe diagnosis of diabetes mellitus from skeletal remains is very difficult given the complexity of the disease and the fact that there are no pathological skeletal characteristics exclusively associated with the condition.[36] Skeletal identification of diabetes mellitus may only be possible through differential diagnosis, when several pathological changes are present. Skeletal and dental changes associated with diabetes mellitus include Charcot's joint (neuropathic arthropathy), osteoporosis, osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH, or Forestier's disease), adhesive capsulitis (frozen shoulder), dental caries, periodontal disease, and antemortem tooth loss.[37]It should not be understood that Neanderthals had diabetes. Type 2 diabetes is a disease of the modern world, borne of a mismatch between modern, unhealthy lifestyles and a metabolism that, for the vast majority of our evolutionary history, existed in an environment where food was relatively scarce and lots of physical activity was necessary to survive.[38] In the harsh environment of the Ice Age, even individuals carrying genes that contribute to diabetes when food is plentiful and sedentary lifestyles are common are unlikely to develop diabetes.Skeletal remains of an adult male from the Egyptian archaeological site of Dayr al Barsha dated to the Middle Kingdom (ca. 2055–1650 BC), display a myriad of pathological conditions that, when considered together, indicate the presence of diabetes mellitus.[39] This diagnosis represents the earliest, and possibly the only recorded, archaeological Raf inhibitor skeletal evidence for this disease.(Ancient Mummy Suffered Rare And Painful Disease)Around 2,900 years ago, an ancient Egyptian man, likely in his 20s, passed away after suffering from a rare, cancer-like disease that may also have left him with a type of diabetes. His mummy showed telltale signs that he suffered from Hand-Schuller-Christian disease an enigmatic condition in which Langerhans cells, a type of immune cell found in the skin, multiply rapidly.[40] They tend to replace normal structure of the bone and all other soft tissues.The disease seems to have taken a terrible toll on the ancient man’s body, as it destroyed parts of his skeleton, leaving lytic lesions throughout his spine and skull.[41] Scans also indicated what looks like a giant hole in his skull’s frontal-parietal bone, and destruction of a section of one of his eye sockets, known as the orbital wall. The effects of the disease would have been excruciating and would have affected the man’s appearance. In addition, it may have led him to suffer from a form of diabetes. The scans show that his sella turcica, part of the skull that holds the pituitary gland, is shallow, which suggests that this gland was also affected by the disease.[42]Researchers believe the condition could have lead to diabetes insipius. The condition would have made it difficult for his kidneys to conserve water, something that would have worsened the man’s predicament.[43] In all likelihood, he suffered from continuous thirst and hunger, urinating frequently.Hatsheput (Metropolitan Museum of Art - Wikipedia)Recent examination of a mummy considered to be Hatshesput (Pharoah of the XVIIIth dynasty 1503 and 1482BC) suggests she probably died of an infection caused by an abscessed tooth, with complications from advanced bone cancer and possibly diabetes.[44] Amenhotep III, the ninth pharaoh of the Eighteenth Dynasty of Egypt, may have suffered from diabetes as well.[45]Archaeological evidence indicates that certain groups of Paleo-Indians maintained an arctic-like hunter-gatherer life-style in temperate areas of North America ranging from Wyoming to Arizona. This life-style featured a reliance on unpredictable big game species as a major food source. However, at this time, big game species were becoming extinct. It is hypothesized that those Paleo-Indians who relied on big game as a food source developed a “thrifty” genotype,[46] that allowed a selective advantage during the periods of fasting that occurred between big game kills.Insulin resistance has previously been proposed as a mechanism for coping with variable food intake during evolution. Neel's thrifty gene hypothesis postulates that cycles of feast and famine selected for a “quick insulin trigger” (postprandial hyperinsulinemia) as a mechanism to increase fat stores during food abundance and available during food scarcity.[47]There is a high prevalence of (Non-Insulin Dependent Diabetes (NIDDM) susceptible genotypes in several distinct populations: American Indians, Australian Aborigines, and Pacific Islanders.[48] The susceptible genotype may have been selected into these populations because of unusually frequent food shortages that occurred during the initial colonization of 'new worlds'. NIDDM has been shown to have a strong genetic component that may include a 'thrifty' genotypes.[49] The 'thrifty' genotypes may have once allowed founding populations to survive feast' and 'famine' conditions for several generations. With an assured food supply and a sedentary lifestyle, however, the 'thrifty' genotype(s) becomes disadvantageous, leading to obesity, increased insulin resistance, beta cell decompensation, and NIDDM.[50]New DNA techniques will spark archeology revolution, expert saysDuring the same time period, across the Atlantic Ocean, it is believed that inhabitants began to exhibit symptoms of what would eventually be classified as Juvenile diabetes. During a 1000 year climatic reversal known as the Younger Dryas, temperatures dropped by 10 degrees Fahrenheit, causing those who did not die from the artic conditions to move South.[51] Researchers from Mount Sinai School of Medicine of New York suggest that some individuals adapted to the extreme conditions. High levels of blood glucose prevent cells and tissue form forming ice crystals. Basically, Type 1 diabetes prevented some from freezing to death.[52]Food during the last Ice Age was almost certainly limited, meaning that dietary blood sugar likely followed suit. Therefore, the insulin of a diabetic from this epoch may have never come close to reaching dangerous levels.The following quote is from Sharon Moalem:Imagine that some small group of people had a different response to the cold. Faced with year-round frigid temperatures, their insulin supply slowed, allowing their blood sugar to rise somewhat. As in the wood frog, this would have lowered the freezing point of their blood. They urinated frequently, to keep internal water levels low… Suppose these people used their brown fat to burn that oversupply of sugar in their blood to create heat. Perhaps they even produced additional clotting factor to repair tissue damage caused by particularly deep cold snaps. It’s not hard to imagine that these people might have had enough of an advantage over other humans… to make it more likely that they would survive long enough to reach reproductive age.”[53]Many in the medical community are skeptical, asserting that the study fails to account for dangerous complications such as ketoacidosis and early death.[54] However, since the average age of death was 25, those with high glucose would not have lived long enough to succomb to complications. They would however, despite the extreme conditions, live long enough to reproduce, resulting in genetic adaptations over a few generations.[55]While this may sound highly speculative, there’s actually a decent amount of evidence to support the notion. Lab rats essentially become diabetic (that is, they grow resistant to their own insulin) when exposed to cold temperatures.[56]More Northern Hemisphere inhabitants are diagnosed with diabetes between November and February than between June and September, theoretically due to the noticable drop in temperature during the former period.[57] Almost invariably, children are diagnosed with Type 1 diabetes during the late fall as temperatures drop. An extensive study of U.S. veterans, revealed that not only do the subjects’ blood sugar levels spike while winter is at hand, but that those who hail from environments with a great deal of variation in seasonal temperature (ie: colder districts) had a particularly extreme physiological contrast in this regard.[58]Footnotes[1] Aretaeus of Cappadocia[2] Polyuria - Genitourinary Disorders - Merck Manuals Professional Edition[3] MECHANISMS OF PAIN FROM URINARY TRACT INFECTION[4] The Ebers Papyrus: Medico-Magical Beliefs and Treatments Revealed in Ancient Egyptian Medical Text[5] Historical Diabetes Remedies[6] Diagnosing Diabetes: A Practitioner's Plea: Keep It Simple[7] The History of Diabetes Mellitus[8] History of Diabetes Mellitus[9] https://mysugr.com/en/blog/ants-with-diabetes[10] https://www.nhp.gov.in/Madhumeha-(Diabetes-mellitus)_mtl[11] https://www.google.com/url?sa=t&source=web&rct=j&url=http://www.jsirjournal.com/Vol4_Issue4_08.pdf&ved=2ahUKEwiqseuKlpzlAhUQpJ4KHWgLBZ8QFjAFegQICxAB&usg=AOvVaw275X45OeYFJcauml-J1PW7[12] Diabetes in Ancient Literature[13] Diabetes Detectives[14] The Origins of Diabetes | St. Hope Foundation[15] The Discovery of Insulin: An Important Milestone in the History of Medicine[16] Diabetes Its Medical and Cultural History[17] Inflammation, Insulin Resistance, and Type 2 Diabetes: Back to the Future?[18] https://www.google.com/url?sa=t&source=web&rct=j&url=https://friedmanfellows.com/assets/pdfs/elibrary/Principles%2520of%2520Diabetes%2520Mellitus%2520-%2520Ch1Final.pdf&ved=2ahUKEwiM6b2smJzlAhXYvJ4KHSVgCQEQFjAKegQICRAB&usg=AOvVaw0kllZ_wHWefc_uHQif9Eqd&cshid=1571071278134[19] Aretaeus of Cappadocia and the first description of diabetes.[20] Aretaeus of Cappadocia[21] History of diabetes: early science, early treatment, insulin[22] On the term diabetes in the works of Aretaeus and Galen | Medical History | Cambridge Core[23] Xiaoke, a traditional Chinese treatment for diabetes. Studies in streptozotocin diabetic mice and spontaneously diabetic BB/E rats.[24] Xiaoke Tea, a Chinese Herbal Treatment for Diabetes Mellitus[25] Dark Ages of Diabetes[26] https://www.google.com/url?sa=t&source=web&rct=j&url=https://vanderbilt.edu/olli/class-materials/2017Winter.ISWk1.pdf&ved=2ahUKEwji5NfznJzlAhXuFzQIHRCVBqUQFjACegQIDxAI&usg=AOvVaw1p-b95HZqhfFGFvH7c8NKE[27] The History of Diabetes Mellitus[28] Sickening Sweet[29] Diapedia, The Living Textbook of Diabetes[30] Diabetes and Depression[31] http://diabeteshealth.com/read/2008/12/17/715/the-history-of-diabetes/[32] History of Diabetes[33] Diabetic Coma - an overview[34] https://www.google.com/url?sa=t&source=web&rct=j&url=http://blogs.discovermagazine.com/deadthings/2019/01/30/denisova-cave-dates/&ved=2ahUKEwiE652zoZzlAhWnmuAKHYgmA54QFjAAegQIARAB&usg=AOvVaw3DibYrT_iwjzC4z6WNvVpW[35] Neanderthal genes linked to diseases in modern day humans including[36] Determinants of Bone Strength and Quality in Diabetes Mellitus in Humans[37] Pathological skeletal remains from ancient Egypt: the earliest case of diabetes mellitus?[38] The deep roots of diabetes[39] Skeletal and dental changes associated with diabetes mellitus inc[40] Hand–Schüller–Christian disease - Wikipedia[41] Ancient Mummy Suffered Rare And Painful Disease[42] Ancient Egyptian Mummies Show Signs of Crippling Spinal Disease[43] McDougall Newsletter: May 2011[44] The King Herself[45] Ancestry and Pathology in King Tutankhamun's Family[46] Archaeology of NIDDM: Excavation of the “Thrifty” Genotype[47] Evolutionary origins of insulin resistance: a behavioral switch hypothesis[48] https://www.ncbi.nlm.nih.gov/m/pubmed/1991567/[49] Google Scholar[50] Archaeology of NIDDM: Excavation of the “Thrifty” Genotype[51] Ice Age Diabetics?[52] Is diabetes a result of ice age?[53] Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease[54] Ice Age Diabetics?[55] The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation.[56] Ice Age Diabetics?[57] Diabetic-level glucose spikes seen in healthy people[58] Diabetes in the Military - Learning About Diabetes | Diabetes Self-Management

I was lucky enough to be blessed with a slightly higher IQ so that during my Year 2, I was offered to advance one year, and my proud Dad just said “Why one? Let’s make it two.” So I continued after the first quarter in Year 4, with kids mostly about 2 years older than me. So I completed the entire course in 8 years instead of 10.First of all, the curriculum was compulsory and universal. No bullshit customised courses where a religious body can indoctrinate pupils, or politically correct rubbish. Everyone got to learn from the same source, and if you as a pupil were willing to work, you got great education without any need for tutors, which would get you to any University (except probably just a very few elite ones where some connections or monetary “help” would be needed, such as MGIMO where future diplomats were prepared).Physical education was offered, and if you were willing, you’d easily pass the state-offered GTO (ГТО, Готов к Труду и Обороне — Ready for Labour and Defence) norms and get a (silver or gold) badge. Or you could just ignore it.It was really up to you what you will take with you out of your school years. There was a first set of exams after Year 8, and second, larger, after Year 10 (final year).First set got you an average grade, and if your grades were good, you could go to Year 9 (Девятый Класс), otherwise you were usually expelled and had to go for vocational training, PTU (ПТУ, Профессионально-Техническое Училище = Vocational Technical School, where you’d spend 3 or so years and obtain a working class profession) or Technikum (which got you after four years something akin to Associate degree, or Junior Specialist). The Year 9 was a posher way of life, in just two years you’d be ready to continue education in the Uni, whereas you’d spend 1–2 years more in others and often people wouldn’t continue their education from there to the Uni.So the Year 8 exams were the first bifurcation point. Second point of bifurcation were Year 10 exams.These grades defined your chances to get admitted to the Uni, especially where competition was high. If you had at least 3/4 A grades and rest were B’s (4.75 average), you only would have to take ONE admission exam; at least 1/2 A grades and rest B’s (4.50 average), you’d have to take TWO. Otherwise, all FOUR exams were required to take.Thus, your hard work in school paid off later, at the bifurcation points, enabling you to pursue better careers and have better life.It was not as irreversible as it is in Asia (from what I know about their system). You still could join the Uni later, while already working, going there in the evenings. However most diplomas obtained in such a way were implied to be “second-grade”.Everyone was matched with their level. There would be normal schools; schools with advanced tuition of certain disciplines (like physics and math — the one I was in, chemistry, foreign languages, sports, music, Russian and literature); and schools for differently abled pupils which required more work; and finally, boarding schools for difficult children who required strict handling.Experienced teachers had quite relaxed communication with the pupils and made learning interesting. Less experienced ones could be boring or outright scary (Pulse 160 waiting for next pupil to be randomly called), but at least visibility of respect was always maintained.The teachers weren’t super strict, just human, and there were good and bad ones, however certain discipline was expected. This is one of the first differences from modern schools. Teachers and principals had quite a few ways to maintain discipline in class (but due to rarity, the top-tier “tools” were very seldom required, and usually good humour did it, with most punishments only required for really disruptive pupils).There were no corporal punishments in school (unlike say, English schools of same periods), but there could be absolutely no confusion about teacher/pupil roles, with no bullshit “equality”, and most teachers were well prepared for the role (being taught in Unis according to a unified curriculum themselves! so the good standards were there), usually did a good job of maintaining a focused, quiet environment where people could learn. They could occasionally slap the back of your head in case of really rotten behaviour, and there would be no stupid lawsuit like in States, but more, parents normally were supposed to help to maintain academic successes.You had normally to have a Uni degree to teach in schools. No such things as God knows who, coming to teach kids…Discipline-wise again.I can’t imagine a pupil telling a teacher to bugger off, or come stoned to the class, or start shooting. These things would be punished to the higher extent in school — a harsh talk with the principal, detention after lessons, lowering behaviour grades, being expelled from school for a week, or even being registered with the police young offenders scheme (which could seriously impede your future life & career). Oh, and it will be made known to your parents, who (if they weren’t good-for-nothing pieces of slime) would shred your arse to pieces at home, so you won’t be able to sit for a week. Who needs corporeal punishments in school, if they are well delegated to parents :) There was no bullshit “positive parenting”, again parent/child roles were there, no fraternising with the enemy :))The homework was there, but nothing remotely harsh. Usually one-two hours a day were all I needed to finish it, I’d call that a good work/life balance :) Enough to maintain interest and progress well in your studies, not enough to make you bored and resentful.And then we were completely free to wander the streets (70’s, no telephone at home, no mobile in my hand, just knock the friend’s door and there you go, always with friends, long hours spent outside, fresh air, any temperature you’re out, on your own, without bullshit rules “kids below 11 can’t walk alone”… usually Year 4–5 kids, so 10–11 years, were out entire evenings, and no one cared unless they didn’t return at dusk. Can’t recall any obese or even overweight kids around! Lots of running, no TV, no iPads and no Xboxs to veg at, only hardcore physical activity — bikes in the summer, skis, skates and sliding from the hills in the winter (which was 3–4 real months in St. Petersburg where I was from).The main conclusion (TL;DR) is:The curriculum was there, universal, approved at the top, perfectly capable of educating you to join the Uni and real life after just 10 years — should you accept the challenge and be willing to do what was required.There was good discipline and decent teacher levels usually, with proper adult/pupil roles firmly set, creating focused and result-oriented environment in schools. Grades mattered (if you cared about your life), your hard work paid off later in life.All the above is about life in a 2nd largest Soviet city, Leningrad (now St. Petersburg). As everywhere, conditions in a small rural community could be very different — just think of comparing San Francisco, CA and Nowheretown, AR. This last note is for those who will want to start arguing ardently that their experiences were nowhere close to what I’ve described and that Soviet education was shit and I’m a liar. Just don’t bother, save your breath, better describe your experiences objectively, good and bad.

Questions about the pineal gland or so-called “third eye” in humans come up so often in Quora that I’m attempting here to consolidate my previous answers into one general-purpose overview. I’ve put in section heads to help navigate to whatever point may be most relevant to what anyone asks. If your interest is mainly in calcification, “opening” the pineal gland, or the “third-eye” interpretation, you can scroll directly to headers on those and skip the introductory biology.I. What Is the Pineal Gland?The pineal gland is a very small gland, 5 to 8 mm long, in the endocrine system of most vertebrate animals from fish to primates, including humans. It’s named for its resemblance to a pine nut (not a pine cone, as so often misstated). It’s also called the epiphysis cerebri, perhaps a useful search term if you ever go looking for further information on it. In fish, amphibians, and reptiles, the pineal gland is located near the brain surface just under the cranium, but in mammals, growth of the cerebral hemispheres has resulted in it being buried deep in the brain (Figure 1).Figure 1. Human Pineal Gland (at arrow). Compared to Mediterranean Pine Nuts (Pignolias).[1] Brain photo from Quizlet via Google Images (no good URL)..II. What Does the Pineal Gland Do?The pineal gland secretes the hormone melatonin, which is concerned with circadian and seasonal rhythms of physiology and animal behavior. The pineal synthesizes melatonin from the neurotransmitter serotonin. Daily melatonin secretion peaks about 3 to 5 hours after one falls asleep, and its level fluctuates seasonally. In animals with seasonal breeding, it regulates the gonads and onset of breeding behaviors, and it’s involved in seasonal migrations of many species. Some physiologists think the human pineal gland plays a role in the onset of puberty, but the evidence for this is inconclusive. Pineal tumors are sometimes associated with precocial (premature) puberty in young boys,[2] but it’s unclear whether they are the direct cause or whether that results from damage to adjacent brain tissues.In humans, melatonin receptors are widespread throughout the body, including the insulin-producing islet cells of the pancreas. A defect in melatonin receptors reduces the body’s sensitivity to insulin and is associated with type 2 diabetes mellitus. Melatonin has also been implicated in mood disorders such as jet lag, seasonal affective disorder (SAD), and premenstrual syndrome (PMS). However, there is also evidence against its role in any of these, so the jury is still out on that question. Nevertheless, many people claim melatonin to be effective for them in relieving jet lag or aiding sleep. (I have used it myself for sleep.).III. What Is the Structure and Composition of the Pineal Gland?Under the microscope (Figure 2), the pineal gland isn’t a very remarkable or exciting-looking organ, even to those of us who do find excitement in the histology of most organs. Almost every organ looks far more interesting than this under the microscope. The pineal consists mostly of tiny melatonin-secreting cells called pinealocytes, intermingled with supportive cells, neurons, and neuron-like cells.Figure 2. Histology of the Human Pineal Gland. Low and high magnifications.[3]A more interesting feature seen in many tissue sections, however, is accretions called corpora arenacea[4] (singular, corpus arenaceum), also called acervuli (Figure 3). Corpora arenacea translates as “sand bodies” and even some biological authorities refer to these granules as “brain sand,” but that’s only a figure of speech. It leads some people to ask me why the brain contains quartz,[5] like beach sand. Quartz, however, is silicon dioxide (SiO2). Corpora arenacea, on the other hand, are composed of calcium phosphate, calcium carbonate, magnesium phosphate, and ammonium phosphate. Acervuli translates as “little heaps” and is a term also used in botany.Their functional significance, if any, is unknown. With age, they accumulate in the pineal gland and some other brain tissues such as the choroid plexuses. They’re often visible on brain CT scans (Figure 4) by one’s twenties or thirties and thus serve as a radiologic landmark for the location of the pineal. This is what is meant by pineal gland calcification; more on that later.Figure 3. A Pineal Corpus Arenaceum[6] (L) compared to silica (quartz) beach sand[7] (R). Other than being hard granules, there is no resemblance physically or chemically. Beach sand made of pulverized coral and mollusc shells, however, is more chemically similar (calcium carbonates and phosphates) to corpora arenacea.Figure 4. Calcified Pineal Gland (arrow). CT scan of a 63-year-old man. The pineal here is about 7 mm dia.[8] This is sometimes helpful as a radiologic landmark for brain surgery on surrounding tissues..IV. Is the Pineal Gland a Photoreceptor?Humans and other mammals don’t have photoreceptor cells in the pineal gland, but many other vertebrates do. In some fish and most amphibians and reptiles, the pineal is associated with a parietal eye (or colloquially, “third eye” or “pineal eye”) (Figure 5), which contains photoreceptor cells and responds directly to light. There is commonly a thin, transparent area of cranium or a translucent reptilian scale over the parietal eye to give these receptors direct access to sunlight, and in some cases, the pineal gland even protrudes through the skull.Figure 5. Parietal “Third” Eye. L: The bullfrog, Rana catesbiana.[9] R: A lizard, the tuatara, Sphenodon punctatus.[10]The pineal photoreceptor cells of these vertebrates are strikingly similar in some ways to the receptor cells of a retina (rods and cones), especially in their elaborate parallel layers of membrane loaded with visual pigment (Figure 6).Figure 6. Receptor Cells in the Parietal Eye of the Lamprey, Petromyzon.[11] The outer segment (OS in figure B) contains closely spaced membrane layers loaded with visual pigment, like the outer segment of human rods and cones. It is the dense, dark cap on the cell in figure C.In humans and other mammals, however, there is no parietal eye and the pineal gland has no such cells. The skull is too thick and the cerebral hemispheres too massive to allow any light to reach the mammalian pineal gland. A Quora question once asked of me cited an article, “Photoreceptors in pineal gland and brain,” and asked, “Why do people claim that the pineal gland doesn’t have photoreceptors, when research clearly shows otherwise?”[12] Another, citing the same article, asked, “Why would we have photo (color) receptors inside of the pineal gland?”[13]What these questioners overlooked, however, is that those researchers, Okano and Fukada (2000),[14] were studying conelike receptor cells in the pineal glands of more primitive vertebrates (amphibians and reptiles), not humans or any other mammals. Okano and Fukada wrote, “Extracranial pineal organs of submammalians are cone-dominated photoreceptors sensitive to different wavelengths of light” (my added emphasis). They clearly imply that mammals such as ourselves have no such pineal cone cells or color-sensitive pigments. A few lines later, they state “the mammalian pineal is considered by most of the authors as a light-insensitive organ.”[15] In my literature search, the only references I could find to direct pineal sensitivity to light in the endothermic vertebrates pertained to birds..V. Does the Pineal Gland Indirectly Receive Any Information on Environmental Light?Yes, apparently it receives information from the eyes by an indirect route. In the retina, there’s a row of neurons called ganglion cells whose axons form the optic nerve. Most of these synapse in the lateral geniculate nucleus of the thalamus with neurons that continue to the visual cortex of the brain at the back of the head, where we become conscious of seeing something.Figure 7. Histology of the human retina.[16]However, some of the ganglion cells contain their own photosensory pigment, melanopsin, different from the rhodopsin of rods and photopsin of cones. The signals from these ganglion cells travel not to the visual cortex but to brainstem centers that control pupil diameter and to pathways to the pineal gland. These fibers end in an area of the hypothalamus called the suprachiasmatic nucleus, which is involved in our circadian biological clock. A second neuron descends from here down the brainstem and spinal cord, exits the spinal cord in the upper thoracic region, then travels up a chain of sympathetic ganglia to one called the superior cervical ganglion. From here, fibers re-enter the cranial cavity and go back to the pineal gland. The pineal gland thus gets information about the daily cycle of light to darkness, L:D ratio, in our environment. Animal brains use this information about seasonal changes in day length for purposes ranging from fattening up for the winter to migrating to warmer climates. The functional significance of this pathway in humans is unknown..VI. Why Is It Called “The Third Eye”?—Pineal Philosophy and MysticismThe pineal gland was known even as far back as ancient Hellenic physicians and anatomists such as Galen (129–c. 200 CE). It’s not clear who named it, but Galen already knew of it and said it was named for its resemblance to the Mediterranean pine nut (see figure 1).[17] Being so small and deeply embedded in the brain, the pineal gland is one of its most inaccessible objects of study and historically lent itself to more philosophical speculation than empirical science. It’s solitary nature and central location led philosopher René Descartes (1596–1650) to consider it the seat of the human soul. He thought that nerves carried sensations to the pineal gland, causing it to vibrate a little bit, and these vibrations were what we perceive as ideas, thoughts, and memories (M. Catani & S. Sandrone, Brain Renaissance, Oxford Univ. Press, 2015).The idea of a third eye comes from the ancient mystic traditions of India and China—from Hinduism, Buddhism, Taoism, and Zen. These traditions regarded it as an invisible spiritual eye, the gateway to higher consciousness, the sixth chakra of Hinduism. They believed it to be located in the forehead between the two visible eyes—which is nowhere near the pineal gland at the rear of the brain. The third eye notion was popularized in the West by the New Age philosophy emerging in the 1970s with renewed interest in Eastern spiritualism.[18] Religious icons depicting the third eye sometimes bear noticeable resemblance to the parietal eye of nonmammalian, nonavian vertebrates (compare Figure 8A to Figure 5).Figure 8. The Third Eye in Iconography. A: Bust of Shiva from late 9th to early 10th century Cambodia; from the collection of the Musée Guimet in Paris.[19] B: Third eye of Shiva.[20] C: Third eye in New Age poster art.[21]The Russian theosophist Madame Blavatsky (1831–1891) proposed that the mystical third eye of antiquity was in fact the pineal gland known to science.[22] In recent times, spawning a lot of questions in Quora and elsewhere, many self-styled mystics, gurus, spiritual leaders, and writers have commercialized and promoted the notions of “awakening” or “opening” the third eye. Apparently this is profitable, as people will fall for anything (just ask P.T. Barnum). Many seem to be conflating this imaginary eye with the anatomical pineal eye demonstrated in diverse nonmammalian animals, or offering scientific knowledge of the parietal eye as supposed “proof” of what the mystics have said for centuries. They falsely assume that since the pineal gland of other animals is light-sensitive, the human pineal gland is too.Figure 9. Some Popular Books on the Pineal “Third Eye.”.VII. How Can I Open or Activate My Pineal Gland?This is a very common Quora question.[23][24] The answer is, you can’t open it. There’s nothing to open (see figure 2). The idea of opening the pineal gland, supposedly to achieve more spiritual awareness, stems from the unsupported idea of the pineal being an eye. One might obtain spiritual awareness or enlightenment through various meditation techniques from Kundalini Yoga to Transcendental Meditation, and I mean no criticism here of that goal or those methods, but it has nothing to do with the pineal gland. The idea of opening the pineal gland might be construed only metaphorically, but if meant literally—a physical opening that one might observe in pineal autopsies of people who died “enlightened”—I would have to dismiss that as pseudoscientific mumbo-jumbo. If such a hypothesis can’t be tested and supported by empirical evidence, then it’s of no value as objective knowledge.The notion of “activating” the pineal gland apparently originate with Rick Strassman’s book, DMT: The Spirit Molecule (2000)[25] claiming that the pineal gland secretes N, N-dimethyltryptamine (DMT). DMT has been used as a recreational drug since the 1960s for psychotropic effects that some users describe as out-of-body or psychedelic experiences[26] or “getting in touch with external realities.”[27] Strassman relates DMT to alien abduction experiences and speculates that it “facilitates the soul's movement in and out of the body.” I find such fancies of little value, no more worth pursuing than Uri Geller or Eric Von Däniken.DMT occurs in trace amounts in the pineal glands of rats, but it’s not clear that the pineal gland is the source of it; it occurs in other brain regions as well (such as the visual cortex) and it’s present in the same amounts with or without the pineal gland (as found in pinealectomized rats). The mRNA that codes for a DMT-synthesizing enzyme, INMT, occurs in the human pineal gland but also in many other tissues throughout the body, and has other functions beside producing DMT.[28] DMT itself has not been detected in the human pineal gland or brain. The pineal gland produces about 30 micrograms of melatonin per day, and would have to quickly produce 25 milligrams of DMT (a thousand times as much in a small fraction of the time, since it breaks down quickly) to reach the threshold for any psychedelic experience.[29][30] This is implausible, to say the least..VIII. Can I Regulate My Pineal Gland?The only way I’ve heard of to artificially regulate the pineal (modify its function) is phototherapy. Bright light suppresses melatonin secretion and has been found to improve sleep and relieve depression in people who don’t get enough natural sunlight. Night-shift workers, for example, often don’t get enough natural light because they’re awake and working during the night, and sleeping by day while the sun is shining. Sleep disturbance and mood disorders can sometimes be relieved by a brief period (as little as 30 minutes) of bright light per day.I couldn’t readily find good information about options, but I see some companies selling “light boxes” for this (lying down with your head in a box with bright lights); I don’t know if this is effective or just a quack capitalization on popular belief. I’ve heard of some companies (factories, hospitals, etc.) that have night-shift workers offering phototherapy rooms—a small room with bright fluorescent lights all along the walls—where employees can go for a half-hour or so of phototherapy before they go home, said to improve sleep and mood through its action on the pineal. However, failure to find significant results in placebo-controlled trials, combined with concerns about overriding harmful effects, has led to the closing of light-therapy clinics in Sweden.[31].IX. How Can I Decalcify My Pineal Gland?The pineal gland becomes progressively calcified with age, accumulating corpora arenacea even in childhood. These form even in birds but not in any of the other vertebrate groups from fish to reptiles.[32]Other questions have arisen on my feed about whether this is has any effect on pineal or brain function, whether it is harmful, whether fluoride in drinking water affects it, and whether it can be reversed or there is any reason to reverse it.Fluoride does seem to contribute to pineal calcification, as discussed in a study of merganser ducks by Kalisinska et al. (2014)[33] with implications for the mammalian and human pineal. These authors speak in paragraph 4 of neurotoxic effects of fluoride in the brains of mammals like ourselves. In the sparse literature available to date, the reported effects on mammalian brains seem to center on oxidative stress and apoptosis (death by “programmed suicide”) of neurons. Half a dozen of Kalisinska’s references point to putative connections with deficits in learning and memory.As to whether pineal calcification can be reversed or there’s any need or reason to do so, I find little information except for unsubstantiated fad diets and dietary supplement ideas, such as doing it with daily doses of apple cider vinegar—sheer nonsense. The idea is supposedly that malic acid in the vinegar will dissolve the calcium granules in the pineal gland. Vinegar certainly will dissolve calcium salts—anything from antacid tablets to blackboard chalk to animal bones—but a little vinegar taken orally won’t affect body pH and will never get anywhere near the pineal gland. If, hypothetically, it did have the ability to dissolve “brain sand,” it would also have the undesirable effect of softening one’s bones (osteomalacia), and would be bad advice.Many other web sites on the subject have agendas like selling special water filters, blue-blocking eyeglasses, detox regimens, and snake-oil remedies like “Activator X” (yes, a real trade name of one of these). This search leads down a murky rabbit hole of pseudoscience and quackery on which I don’t care to waste any more time and nobody should waste their money.I did find one credible, peer-reviewed article on pineal calcification with a section on hypothetical and empirical pineal rejuvenation. On the empirical side, though, this involved studies in which young pineal glands were transplanted into the eyes (!) of older rats and showed some rejuvenating effect, or in which cells were injected into the pineal glands of chicks (which, unlike the human pineal, are close to the brain surface and easy to access). On the hypothetical side, there is some speculation on whether there are any plausible ways to rejuvenate aging human pineal glands by cell injection or perfusion techniques,[34] but obviously this is no do-it-yourself job..CodaI hope this answers most questions people have about the pineal gland. If new questions, facts, or corrections arise, I’ll edit and update this to whatever extent I feel they may warrant.Footnotes[1] Mediterranean Pine Nuts (Pignolias) | Pine Nuts | Nuts.com[2] Precocious Puberty Due to Human Chorionic Gonadotropin-Secreting Pineal Tumor - PubMed[3] Pineal gland - Wikipedia[4] Corpora arenacea - Wikipedia[5] Why does the pineal gland have quartz in it?[6] Description[7] Microbus Microscope Educational Website[8] Diagnostic accuracy of susceptibility-weighted magnetic resonance imaging for the evaluation of pineal gland calcification[9] Parietal eye - Wikipedia[10] Sphenodon punctatus - Monaco Nature Encyclopedia[11] Figure 10. [Lamprey pineal photoreceptors. A, Schematic...].[12] Why do people claim that the pineal gland doesn’t have photoreceptors, when research clearly shows otherwise?[13] Why would we have photo (color) receptors inside of the pineal gland?[14] [17] Photoreceptors in pineal gland and brain: Cloning, localization, and overexpression[15] (PDF) Nonvisual photoreceptors of the deep brain, pineal organs and retina[16] Anatomy & Physiology: The Unity of Form and Function[17] Descartes and the Pineal Gland[18] New Age - Wikipedia[19] Third eye - Wikipedia[20] Third Eye GIF - Find & Share on GIPHY[21] What is the Third Eye and How can it be opened? What are the benefits?[22] The Secret Doctrine[23] People often talk about the pineal gland. How can a person open the pineal gland? What are the benefits?[24] Is it really possible to open/activate your pineal gland? Or is it a gimmick?[25] DMT: The Spirit Molecule[26] What Is DMT? Everything You Need to Know[27] N,N-Dimethyltryptamine - Wikipedia[28] Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain[29] No reason to believe the pineal gland alters consciousness by secreting DMT, psychedelic researcher says[30] N,N-dimethyltryptamine and the pineal gland: Separating fact from myth - David E Nichols, 2018[31] Light therapy - Wikipedia[32] Comparative Histology of Pineal Calcification - PubMed[33] Fluoride concentrations in the pineal gland, brain and bone of goosander (Mergus merganser) and its prey in Odra River estuary in Poland[34] Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland