{"id":43765,"date":"2018-12-21T12:11:33","date_gmt":"2018-12-21T11:11:33","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=43765"},"modified":"2019-01-04T17:41:32","modified_gmt":"2019-01-04T16:41:32","slug":"jeffrey-aronson-when-i-use-a-word-treating-convulsions-in-1618-human-skull","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2018\/12\/21\/jeffrey-aronson-when-i-use-a-word-treating-convulsions-in-1618-human-skull\/","title":{"rendered":"Jeffrey Aronson: When I use a word . . . Treating convulsions in 1618\u2014human skull"},"content":{"rendered":"<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-32935\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson-223x300.jpg\" alt=\"jeffrey_aronson\" width=\"122\" height=\"146\" \/><\/a><span style=\"font-weight: 400\">Before 2018 ends, I want to celebrate again the grandfather of UK pharmacopoeias, the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia Londinensis<\/span><\/i><span style=\"font-weight: 400\">, whose first edition was published in 1618 in two separate versions (Box 1). Its contents give some surprising insights into medical practice at that time.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Among the many remedies listed in the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia<\/span><\/i><span style=\"font-weight: 400\">\u2014the roots, barks, woods, leaves, flowers, fruits and buds, seeds or grains, tears, juices, plant extracts, things from the sea, salts, and metals\u2014one section stands out, that devoted to \u201cAnimal parts, excreta, and tissues\u201d, where we learn about unusual applications of strange medicaments: the shells of certain mussels; the abdomen and tail of lizards; the lungs of fox, lamb, hog, and bear; grease of duck, goose, and bear; fat of hog, viper, calf, and boar; suet of buck, goat, stag, ox, sheep, cow, and badger; marrow of ox, sheep, lamb, stag, dog, goat, cow\u2019s shin bones, bull, and calf; bile of bull, cow, hawk, kite, goat, hog, and hare. Disappointingly, eye of newt and toe of frog did not feature, even though Shakespeare\u2019s <\/span><i><span style=\"font-weight: 400\">Macbeth<\/span><\/i><span style=\"font-weight: 400\"> was first performed in around 1606.<\/span><\/p>\n<p style=\"border: 3px;border-style: solid;border-color: #FF#0C0000;padding: 1em\"><b>Box 1. The two versions of the first edition of the <em>Pharmacopoeia Londinensis<\/em><\/b><span style=\"font-weight: 400\"><br \/>\nThe <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia Londinensis<\/span><\/i><span style=\"font-weight: 400\"> was first published by the College of Physicians on 7 May 1618. However, the physicians then claimed that the first edition had been botched at the printers\u2019 shop. They withdrew it, and on 7 December 1618 issued a greatly expanded revised version, which included, for example, 1190 simples, compared with only 680 in the <\/span><a href=\"https:\/\/babel.hathitrust.org\/cgi\/pt?id=mdp.39015072279998;view=1up;seq=9\"><span style=\"font-weight: 400\">earlier version<\/span><\/a><span style=\"font-weight: 400\">. A simple was originally a medicine compounded from a single ingredient, especially a single herb or plant, and hence a plant or herb used medicinally; the term is now obsolete. The physicians claimed in an epilogue that the printer of the earlier version had \u201csnatched away from our hands this little work not yet finished off, \u00a0\u2026defiled with so many faults and errors, incomplete and mutilated because of lost and cut off members\u201d. Which is supposedly why the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia Londinensis<\/span><\/i><span style=\"font-weight: 400\"> had two first editions. Whether this was the true reason is unclear.<\/span><br \/>\n<span style=\"font-weight: 400\">Clare Fowler has <\/span><a href=\"https:\/\/shop.rcplondon.ac.uk\/products\/pharmacopoeia-londinensis-1618-and-its-descendants?variant=12295846494286\"><span style=\"font-weight: 400\">suggested<\/span><\/a><span style=\"font-weight: 400\"> that one of the Fellows of the College, Sir Th\u00e9odore Turquet de Mayerne, prematurely submitted his own version to the printer, to the dissatisfaction of the other Fellows, who replaced it with the later version. <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/11\/02\/jeffrey-aronson-when-i-use-a-word-the-1618-pharmacopoeia-londinensis\"><span style=\"font-weight: 400\">Alternatively<\/span><\/a><span style=\"font-weight: 400\">, the physicians may not have liked the title page in the first version, which, based on a standard format, shows some of the royal symbols, such as the lion and the unicorn, but not the King\u2019s or the College\u2019s coat of arms. The King himself, James I, may have been displeased with the first version\u2014he had issued a proclamation that \u201call Apothecaries of this Realme [should] follow this Pharmacopoeia \u2026 upon paine of our high displeasure\u201d, but the proclamation was inadvertently omitted from the early impressions of the May edition. Another reason for blaming the printer, Edward Griffin.<\/span><\/p>\n<p><b>Human skull as an anticonvulsant<\/b><\/p>\n<p><span style=\"font-weight: 400\">Man as an animal whose parts might form the source of medicaments is not neglected in the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia<\/span><\/i><span style=\"font-weight: 400\">. In the December 1618 version we read of the use of \u201cCranium Humanum, In Eo Os Triquetrum\u201d. The os triquetrum, or triangular bone (Latin triquetrus, three-cornered), is in this case one of what are now called Wormian bones, named after the Danish physician Olaus Worm (1588\u20131654), found in the sagittal suture; it is not to be confused with the triquetrum, a triangular bone in the wrist. Pliny the elder (23\u201379 AD) mentioned the therapeutic use of human skull in his 10 volume encyclopaedia, <\/span><i><span style=\"font-weight: 400\">Naturalis Historia<\/span><\/i><span style=\"font-weight: 400\">, which contains 37 books on astronomy, mathematics, geography, ethnography, anthropology, human physiology, pharmacology, zoology, botany, agriculture, horticulture, mining, sculpture, painting, mineralogy, and precious stones, published posthumously: \u201cFor epilepsy, Artemon has prescribed water drawn from a spring in the night, and drunk from the skull of a man who has been slain, and whose body remains unburnt\u201d (Book XXVIII, Chapter 2). <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25479153\"><span style=\"font-weight: 400\">After that<\/span><\/a><span style=\"font-weight: 400\"> many other physicians used human skull to treat epilepsy, even as late as the 18<\/span><span style=\"font-weight: 400\">th<\/span><span style=\"font-weight: 400\"> century. <\/span><\/p>\n<p><span style=\"font-weight: 400\">Take a late 17<\/span><span style=\"font-weight: 400\">th<\/span><span style=\"font-weight: 400\"> century example. Powdered skull in water was among the many herbs and other remedies that his physicians ventured to use when Charles II fell ill with convulsions on 2 February 1685; after that he had no more convulsions, whether because of or in spite of the treatment is unclear. The method had been described by <\/span><a href=\"https:\/\/collections.nlm.nih.gov\/bookviewer?PID=nlm:nlmuid-2548018R-bk#page\/1\/mode\/2up\"><span style=\"font-weight: 400\">Nicholas Culpeper<\/span><\/a><span style=\"font-weight: 400\"> in his 1653 English version of the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia Londinensis<\/span><\/i><span style=\"font-weight: 400\"> (Figure 1).<\/span><\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/12\/aronson_dec21_2018.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-43767 size-full\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/12\/aronson_dec21_2018.jpg\" alt=\"\" width=\"636\" height=\"490\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/12\/aronson_dec21_2018.jpg 636w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/12\/aronson_dec21_2018-300x231.jpg 300w\" sizes=\"auto, (max-width: 636px) 100vw, 636px\" \/><\/a><\/p>\n<p><b>Figure 1.<\/b><span style=\"font-weight: 400\"> Nicholas Culpeper\u2019s English edition (1653) of the <\/span><i><span style=\"font-weight: 400\">Pharmacopoeia Londinensis<\/span><\/i><span style=\"font-weight: 400\">, showing the title page (left) and the first page of the section on Parts of Living Creatures and Excrements (top right), where we read of the efficacy of human skull in treating the falling sickness, i.e. epilepsy (bottom right)<\/span><\/p>\n<p><span style=\"font-weight: 400\">Hoping no doubt to purge him of naughty humours, Charles\u2019s physicians dehydrated him by bleeding, cupping, scarifying, blistering, and clystering him, and they gave him a range of herbs, some innocuous, some potentially harmful, including dehydrating emetics and purgatives, as well as the powdered skull. On Friday 6 February the King apologised to them for having been \u201can unconscionable time dying\u201d; <\/span><i><span style=\"font-weight: 400\">they<\/span><\/i><span style=\"font-weight: 400\"> might equally have apologised to <\/span><i><span style=\"font-weight: 400\">him<\/span><\/i><span style=\"font-weight: 400\"> for their ministrations and for having hastened his death, which was probably in any case unpreventable. Renal insufficiency secondary to gout and dehydration was a <\/span><a href=\"https:\/\/www.cebm.net\/2018\/10\/the-death-of-king-charles-ii\"><span style=\"font-weight: 400\">plausible cause<\/span><\/a><span style=\"font-weight: 400\">.<\/span><\/p>\n<p><span style=\"font-weight: 400\">If extract of human skull were being developed today, it would be necessary first to identify the active ingredient, to test it preclinically, and then to perform the necessary pivotal studies of benefits and preferably also harms, before submitting it for approval to regulatory authorities, such as the UK Medicines and Healthcare products Regulatory Agency (MHRA), the European Medicines Agency (EMA), and the US Food and Drug Administration (FDA). This process would preferably also include studies of the <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29888417\"><span style=\"font-weight: 400\">mechanism of action<\/span><\/a><span style=\"font-weight: 400\">.<\/span><\/p>\n<p><span style=\"font-weight: 400\">A mechanism whereby human skull is efficacious in neurological disorders was proposed by Jan Baptist van Helmont (1580\u20131644) in <\/span><i><span style=\"font-weight: 400\">A Ternary of Paradoxes: The Magnetick Cure of Wounds. Nativity of Tartar in Wine. Image of God in Man<\/span><\/i><span style=\"font-weight: 400\">, as <\/span><a href=\"https:\/\/books.google.co.uk\/books?hl=en&amp;lr=&amp;id=6_RAAQAAMAAJ&amp;oi=fnd&amp;pg=PA1&amp;ots=k8b4ajyJNI&amp;sig=Zjqm7Hsvv8CuwVeyBwDvkzc6UC8&amp;redir_esc=y#v=snippet&amp;q=%22consumed%20and%20dissolved%22&amp;f=false\"><span style=\"font-weight: 400\">translated<\/span><\/a><span style=\"font-weight: 400\"> by Walter Charleton in 1650: \u201call the brain is consumed and dissolved in the scull, by the continual irroration and imbibing of which precious liquor (I mean that of the brain) the scull acquires such virtues, which we have discovered to be wanting to the other bones.\u201d Those interested in new ways of treating epilepsy, dementia, and other neurological disorders might perhaps take note.<\/span><\/p>\n<p><em><strong>Jeffrey Aronson<\/strong>\u00a0is a clinical pharmacologist, working in the Centre for Evidence Based Medicine in Oxford&#8217;s Nuffield Department of Primary Care Health Sciences. He is also president emeritus of the British Pharmacological Society.<\/em><\/p>\n<p><strong>Competing interests:<\/strong>\u00a0None declared.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Before 2018 ends, I want to celebrate again the grandfather of UK pharmacopoeias, the Pharmacopoeia Londinensis, whose first edition was published in 1618 in two separate versions (Box 1). 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Treating convulsions in 1618\u2014human skull - The BMJ","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/blogs.bmj.com\/bmj\/2018\/12\/21\/jeffrey-aronson-when-i-use-a-word-treating-convulsions-in-1618-human-skull\/","og_locale":"en_US","og_type":"article","og_title":"Jeffrey Aronson: When I use a word . . . Treating convulsions in 1618\u2014human skull - The BMJ","og_description":"Before 2018 ends, I want to celebrate again the grandfather of UK pharmacopoeias, the Pharmacopoeia Londinensis, whose first edition was published in 1618 in two separate versions (Box 1). 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