Jeffrey K Aronson

The number three is a powerful guide to formulating slogans, statements of principles, and story telling in all walks of life, including medicine. The statistical rule of three states that the 95 confidence interval of a zero observation is 0–3, so that if you don’t see a particular outcome, such as an adverse reaction, in a clinical trial of an intervention, there is still a chance that it will occur when the intervention is used more widely; thus, if an event is not seen in a study of 100 individuals there is up to a 3% chance of seeing it in practice; if it isn’t seen in 1000 individuals the chance of seeing it subsequently is up to 0.3% and so on. Triadic medical slogans include “see one, do one, teach one”; “history, examination, investigation”; and “percussion, palpation, auscultation.” There is a rule of three that has been applied to fragment-based drug discovery, and the triad that informs subsequent drug development is “quality, efficacy, safety,” although not necessarily in that order. Most clinical syndromes have at least three components, although there are a few with only one or two.I have previously discussed the power that the number three has as a guide in formulating slogans, statements of principles, and story telling.1 Here I concentrate on some of the medical relevance of triads.The term “rule of three” has often been used to describe the principle of concatenating triplets when creating slogans, for example in advertising and other activities.2 However, the most important rule of three, relevant to medicine, is a statistical one,3 as an example shows.If you treat 100 people with an intervention and log all the adverse events that occur, there are many adverse events that never occur. Suppose during a study of an …

A Janus word or phrase has two meanings, each the opposite of the other. Janus words are named after the two-faced Roman god of archways and doors, Janus. There are many such words in English, the classical example being “cleave,” which means to divide or to unite, coming as it does from two different Old English words, cleofan and clifian. However, there are relatively few medical Janus words, which may be just as well, since ambiguity should be avoided whenever possible.Of the IndoEuropean roots from which so many of our English words derive, one of the simplest was the biliteral EI, which meant to go. The Greek derivative of that was ἰέναι, to go, whose present participle ἰόν, going, transliterates directly to “ion” and gives us the two forms of it that go up and down towards an electrode, anion and cation.In Latin the verb became eo, I go, the past participle of which was itum, went. This gives us a long list of words ending in -it and implying some form of going: adit, going towards; ambit and circuit, going around; introit and exit, going in and out; obit, going down; transit, going across. Other it-words include coitus (going together), initial, sedition (going apart), and words beginning with it-, iterate and itinerary.Add a suffix to the basic root, with a slight change in phonation, and you get the root YA-NO, which gives Latin words for ways of going in, ianus and ianua.The Roman god Janus was two-faced, literally rather than metaphorically. He was the Roman god of beginnings and endings, portrayed as having two faces looking in opposite directions. His temple in Rome, the Janus Geminus (literally a twinned archway) was an arched tunnel with a door at either end, east and west. Its doors …

Hospes in Latin means both a host and a guest. It’s a Janus word that reflects a reciprocal arrangement between not so much opposites as counterparts. Hospes gives us the word hospitality, which is what a guest would expect from a host. It also gives us the words hospice and hospital. Although the word “hospitalist” had been used occasionally to mean someone who ran a hospice or a hospital, it had been long obsolete when it was reintroduced in the USA in the late 20th century to describe a general in-house doctor in a hospital responsible for providing complete care for patients with general medical problems, no matter what organ or system was affected. Early reports of the outcomes of instituting hospitalist programmes were generally positive. The Re:State think tank, in a recent report on the UK hospital of the future, has suggested introducing hospitalists here, in order to reduce the problems of internal and external bottlenecks that restrict the flow of patients through and out of the hospital. We therefore have the opportunity to institute a pilot scheme whereby the benefit to harm balance of introducing hospitalists into UK hospitals would be studied, with a view to introducing them widely if the scheme proved to be successful.I have previously discussed Janus words or phrases, also called contronyms or antagonyms, each of which has two meanings, one the opposite or counterpart of the other.1 However, I didn’t discuss the several different ways in which this self-contradictoriness arises.Some Janus words have two different etymologies. Cleave, for example, to divide or to unite, comes from two separate Old English words, cleofan, to divide, and clifian, to unite.Other Janus words come from the fact that an action can be done equally well in two different directions. For example, when …

The original definition of the word “bias,” when it entered the English language in the 16th century, was a diagonal line, and specifically one that cut across the warp or weft of a woven fabric. It later came to mean the tendency of a bowl, the asymmetrically shaped ball-like object used in the game of bowls, to take a curving course when rolled across a lawn, and eventually, among other things, something that produces distortion of a statistical result. Based on a study of its etymology, usages, previous definitions, and sources, I propose the following definition of a bias in research:bias, n. /ˈbʌɪəs/ A systematic distortion, due to a design problem, an interfering factor, or a judgment, that can affect the conception, design, or conduct of a study, or the collection, analysis, interpretation, presentation, or discussion of outcome data, causing erroneous overestimation or underestimation of the probable size of an effect or association [ancient Greek ἐπικάρσιος, crosswise, esp. at right angles, via French biais]This defines the count noun, a bias. The non-count noun, bias, could be defined as a tendency to produce biases.Consider three possible outcomes in an interventional study, investigating, say, a novel medicine. The medicine improves the condition, worsens it, or has no effect. How is each of these outcomes to be explained?In all cases the apparent effect could be real. The drug really does what it appears to do. However, leaving aside the possibility that the positive or negative outcome arose merely by chance, or, in the case of the no-effect result, because the study wasn’t adequately powered to detect a difference, there is always the possibility that a bias or biases of some sort played a part. Perhaps bias enhanced or impaired the response, making it appear that a positive or negative …

My list of medically related anniversaries for 2026 (events in years ending ’26 and’76) includes:• Births: Abū al-Walīd Muḥammad ibn Aḥmad ibn Rushd, the physician better known as Averroes (1126); the Flemish botanist Charles de L'Ecluse (Carolus Clusius) (1576); Amadeo Avogadro, Italian physicist (1776); Johann Spurzheim, German physician (1776); George Birkbeck, English physician (1776).• Deaths: Francis Bacon (1626); Jean Anthelme Brillat-Savarin, French lawyer and gastronome (1826); Friedrich Wilhelm Weiß, German physician and composer (1826); René Laënnec, French physician (1826); Philippe Pinel, French physician (1826); Walter Channing, American physician (1876); Victor Babe ș, Romanian physician and bacteriologist (1926); William Bateson, English biologist (1926); Emile Coué, French pharmacist and psychologist (1926); Camillo Golgi, Italian anatomist (1926); Emil Kraepelin, German psychiatrist (1926); Einar Aaser, Norwegian physician (1976); Andrew Arthur Abbie, Australian anatomist and anthropologist (1976); Jacques Monod, molecular biologist (1976); George Whipple, American physician (1976); Alexander S Wiener, American physician (1976).• Biomedical texts published: Observationes medicae circa morborum acutorum historiam et curationem by Thomas Sydenham (1676); A Comment on Forty two Histories Discribed [sic] by Hippocrates in the First and Third Books of his Epidemics by John Floyer (1726); The botanical arrangement of all the vegetables naturally growing in Great Britain by William Withering (1776); De generis humani varietate nativa by Johann Friedrich Blumenbach (1776); L'uomo delinquente ( Criminal Man ) by Cesare Lombroso (1876); Geographical distribution of animals by Alfred Wallace (1876); The theory of the gene by Thomas Hunt Morgan (1926).• Clinical therapies introduced: George Richards Minot and William Parry Murphy (treatment of pernicious anaemia with liver, 1926).• Biochemical and bacteriological observations: Karl Wilhelm Scheele (uric acid in kidney stones, 1776); Otto Unverborden (discovery of aniline, 1826); Robert Koch (the anthrax bacillus, 1876); James Batcheller Sumner (crystallisation of jackbean urease, 1926).• Establishment of the Edinburgh Medical School (1726) and of The Body Shop (Anita Roddick, 1976).• Epidemics of typhus in Spain (1576) and Ebola virus infection in Yambuku, Zaire (1976).• Nobel prizes for physiology or medicine awarded to Baruch Samuel Blumberg for identifying Australia antigen as an indicator in the blood of hepatitis B and to Daniel Carleton Gajdusek for his work on the origin and spread of infectious diseases, particularly slow virus infections and specifically kuru (both 1926), and to Johannes Andreas Grib Fibiger for discovering the Spiroptera carcinoma (1976).

Psychedelic drugs produce effects on the mind that manifest as an apparent expansion of consciousness often accompanied by hallucinations. Psychedelics, which act as agonists at serotonin 5-HT2A receptors in the brain, include psilocybin, 5-methoxydimethyltryptamine, and N,N-dimethyltryptamine (tryptamine derivatives), mescaline (a phenethylamine derivative), and lysergic acid diethylamide (LSD, a lysergamide). In his long essay The Doors of Perception Aldous Huxley stated that he had always been a poor visualiser and that words did not evoke pictures in his mind. That was consistent with a diagnosis of aphantasia, the absence of a mind’s eye. His description of his disappointing experience with mescaline was also consistent with this. When the psychiatrist Humphrey Osmond, who in 1953 had supplied Huxley with the mescaline and had supervised his use of it, invented the word “psychedelic” to describe the effects of drugs whose actions mimicked those of certain psychiatric disorders, he wrote to Huxley to tell him about it. The combination of Huxley’s aphantasia and his non-hallucinogenic response to mescaline suggests that those who have aphantasia may not respond as dramatically as others do to the actions of psychedelic drugs. However, there have been a few anecdotal reports that aphantasiacs have developed mental imagery after recreational use of a psychedelic drug. Whether psychedelics should or should not be used in aphantasiacs could be tested in formal studies, under controlled conditions, of the therapeutic actions of psychedelic drugs, such as psilocybin and mescaline, in people with the disorders for which they may be beneficial.Aldous Huxley (1894‒1963) is best known as a novelist, particularly for his futuristic science fiction novel Brave New World (1932), although most of his other well known novels were social satires.However, Huxley was also a poet and essayist, his best known essays being two that are often published together: The Doors …

Many terms have been invented to describe different types of hallucinogenic drugs, sometimes based on an analogy with the symptoms of schizophrenia, such as “psychotomimetic” and “phrenotropic.” “Psychedelics” refers to drugs that act as agonists at serotonin 5-HT2A receptors in the brain; they include psilocybin, 5-methoxydimethyltryptamine, and N,N-dimethyltryptamine (tryptamine derivatives), mescaline (a phenethylamine derivative), and lysergic acid diethylamide (LSD, a lysergamide). “Entactogens” refers to drugs that are supposed to touch you within your mind; they act by increasing release of 5-hydroxytryptamine from presynaptic serotonergic neurons and include amfetamine, methylenedioxymetamfetamine (ecstasy, E, MDMA), 5-methoxy-2-aminoindane, and the cathinones methylone and 3-methylmethcathinone. “Oneirogens” refers to drugs that induce a dream-like state similar to the oneirophrenia that is sometimes seen in schizophrenia; they include ibogaine and harmaline alkaloids. “Entheogens” refers to drugs that are used in religious rituals or to elicit a spiritual experience; they include peyote and psilocybin. However, despite the introduction of these and other terms to describe all kinds of hallucinogenic or mind-altering substances, we still don’t understand the pathophysiology of schizophrenia.The word “hallucination” comes from the past participle of the Latin verb alucinari, to wander in one’s mind, to talk idly, or to prattle. The verb to hallucinate first appeared in written English in the first monolingual English dictionary, compiled by Robert Cawdrey, A Table Alphabeticall of 1604, whose full title was A Table Alphabeticall contayning and teaching the true writing and understanding of hard usual English words, borrowed from the Hebrew, Greeke, Latine, or French, &c . Actually, that was just the first paragraph of the title, which went on after that for a further 57 words. Cawdrey defined “hallucinate” as a transitive verb, “to deceive, or blind.”Other dictionaries followed Cawdrey’s, and “hallucinate” appeared again only a few years later, in Henry Cockeram’s English Dictionarie, or …

An antedating, lexicographically speaking, is an earlier instance of the use of a word in a text than had previously been recorded. There are many examples of medical words whose earliest occurrences antedate the earliest examples given in the Oxford English Dictionary ( OED ). To mention just a few examples, they include: drip, antedatable from 1933 to 1920; lymphadenopathy, antedatable from 1920 to 1915; and medicalized, antedatable from 1970 to 1913 (in The BMJ , as it happens). And even earlier instances of those words might yet be discovered. If the several different meanings of “anamnesis,” mostly related to forms of recall, were to be listed separately in the dictionary, several antedatings could also be claimed in relation to its use to mean the medical history. When “placebo” was first treated in the OED in 1907 it was dated to 1811, in Robert Hooper’s Medical Dictionary . In the 1989 second edition, that was antedated to 1785, in George Motherby’s New Medical Dictionary , even though an earlier instance, in the clinical lectures of the Edinburgh physician William Cullen, was already known, and detailed in the James Lind Library. Now the lexicographers have further antedated the word to 1770 in the lectures of another Edinburgh physician, Andrew Duncan the Elder or Primus. Was “placebo” in its modern medical meaning coined in the Edinburgh medical school, which this year celebrates its 300th anniversary?Lexicographically speaking, an antedating is a written example of the use of a word that is of an earlier vintage than was previously recorded in a dictionary. Whenever I have surveyed medical terminology, I have found antedatings of the earliest citations in the Oxford English Dictionary ( OED ) in about 10‒15% of cases. In some cases, these have subsequently appeared in the dictionary, in other cases not. Here are some …

The term “placebo” can be dated back to at least the 1770s, the earliest recorded instances having occurred in the published lectures of two Edinburgh physicians, Andrew Duncan and William Cullen. In contrast, the term “nocebo” dates only from 1961. A nocebo effect or nocebo response can be seen to have occurred when, adapting the Oxford English Dictionary ( OED ) definition, one or more adverse effects are reported after administration of a placebo. Compared with placebos and the placebo effect, nocebos and the nocebo effect have been little studied, and many of the published papers that feature discussion of nocebos are non-systematic reviews. To quote the old academic phrase, which, although trite, on this occasion is nevertheless apposite, “more research is needed.”Tracing the earliest examples of the written use of the word “placebo” has been a relatively slow process. By “placebo” I mean, as it is defined in the Oxford English Dictionary ( OED ), “A drug, medicine, therapy, etc., prescribed more for the psychological benefit to the patient of being given treatment than for any direct physiological effect; esp. one with no specific therapeutic effect on a patient's condition, but believed by the patient to be therapeutic (and sometimes therefore effective). Also: a substance with no therapeutic effect used as a control in testing new drugs, etc.; a blank sample in a test.”1When “placebo” was first treated in the first edition of the OED , in the fascicle Piper‒Polygenistic, published in March 1907, the earliest instance was dated to 1811, in Robert Hooper’s Medical Dictionary , even though earlier versions of the definition used at that time (“An epithet given to any medicine adapted rather to please than benefit the patient”) had been published, going back to 1787.2 In the 1989 second edition of the OED , that …

The number of centenarians in the UK in 1951 was counted at 271. Since then, the number has increased exponentially, with a doubling time of about 12 years; it was estimated at 16 640 in 2024. Different environmental factors will have contributed to this striking increase, but the extent to which each has done so is not known. They include improvements in healthcare, including pharmacological therapies, dietary interventions, and increased participation in forms of exercise, and reduced atmospheric pollution, beginning with the Clean Air Acts of the 1960s. Increased rates of obesity may have militated against the trend, but better treatments may start to reverse that. The association of some genes with certain preventable or treatable diseases, and even the possibility that some genes may be independently associated with longevity, suggests another strategy—that of choosing one’s parents carefully.The hundredth anniversary of the birth of Sir David Attenborough on 8 May 1926 is being celebrated today, justifiably, not merely because of the achievements of the man himself, but also because it reminds us that more people than ever before are living to the age of 100 years and over. Another example, in the medical field, was Harold Ellis, the surgeon whose textbook, Clinical Anatomy , in its 14 editions, has been so influential in teaching generations of medical students, and who died recently having just attained the age of 100. I have just tucked a copy of his obituary into my copy of the 3rd edition of 1966, which opened my eyes to the clinical relevance of the anatomy that I had been struggling to understand in the dissecting room.Those who live to be 100 years old are called centenarians, from the classical Latin adjective centenarius, referring to something that is or contains a hundred of anything, or more specifically, …