Andrew Scull is Distinguished Professor of Sociology and Science Studies at the University of California, San Diego.  His newest book, Hysteria: The Biography, is a volume in our series Biographies of Disease which we will be looking at for the next few week (read previous posts in this series here).  Each volume in the series tells the story of a disease in its historical and cultural context – the varying attitudes of society to its sufferers, the growing understanding of its causes, and the changing approaches to its treatment. In the excerpt below Scull looks at the spectacle hysteria patients provided, specifically the displays by Jean-Martin Charcot.

It was Jean-Martin Charcot (1825-93), the august Professor of Pathological Anatomy and later of Diseases of the Nervous System of the Paris Medical Faculty, the leading international neurologist of the nineteenth century, who made hysteria a spectacle and a circus.  It was a scandalous circus that attracted the attention of  tout Paris, one that regularly featured scantily clad women disporting themselves in unmistakably erotic cataleptic poses, or writhing and moaning in ways that mimicked orgasms on a public stage, before an understandably rapt audience – an audience soon drawn not just from the highest ranks of French society, but also from those attracted to Paris by news of these extraordinary Leçons du Mardi.  The photographs of these occasions, captured in carefully staged arrangements before the supposedly objective lens of the camera and thus transmuted into indelible visual representations for a vastly greater virtual audience, have survived for later generations to inspect, and have become iconic images of a disorder seen as at once sexual and feminine.

Yet Charcot thought of himself, and was acknowledged by his contemporaries, to be no nineteenth-century Mesmer, no marginal charlatan catering to depraved appetites (among patients and audience alike), but on the contrary a sober scientists, a man of genius, one of the leading contributors to the newly emerging science of the brain.  His accomplishments first in internal medicine and then as a neurologist were legion, and had brought him czars and princes, great merchants and bankers, as his clients, in the process making him a very rich man.  And, while his most famous patients were women, he personally insisted…that hysteria was not solely a female malady, but, on the contrary, could be diagnosed and detected among the male of the species.  Hysteria was, he confidently declared, a disorder of the nervous system, not of the female reproductive organs.  It was, moreover, as real and as somatic a disease as any of the other neurological catastrophes he had earlier elucidated….

…Charcot had his favorites, those who returned time and again to put on multiple, often increasingly elaborate, performances.  None was more famous than Blanche Wittman, the queen of hysterics, a performer who luxuriated in her role.  Perhaps the most famous single image of a hysterical patient is an 1887 painting by André Brouillet that captures Charcot presenting Blanche, his pet hysteric, to members of his neurological service.  She swoons over the outstretched arm of his assistant, Joseph Babinski, her pelvis thrust forward, her breasts barely covered by her blouse and pointing suggestively toward the professor, her head twisted to the side and her face contorted in what looks like the throes of orgasm.  (Freud kept a copy of this painting, which dates from 1887, in his study in Vienna, and again in London.)

Wittman was admitted to the Salpêtrière in 1878, and remained there for some sixteen years, performing on command.  After her discharge, she became Marie Curie’s laboratory assistant, and eventually was poisoned by the radium she was working with. In consequence, both legs and her left arm had to be amputated…

The Iconographies, the collections of photographs of the performers who made up the circus, circulated widely and disseminated the Charcotian vision of hysteria to an audience who could only virtually witness the Parisian scene.  They did much to fix the image of hysteria in the public mind, and perhaps to spread suggestively what purported to be neutral, naturalistic recording of a neuropathic disorder.  The photograph (at least before the age of digital manipulation) carried the illusion of providing the truth, a direct and unmediated portrait or even a mirror of nature, the instantaneous representation of what passed before the lens of the camera.  But the limitations of lighting, and the technical requirements of picture-taking with wet collodion plates, or even the later silver gelatino-bromide coating, made for long exposures, sometimes as long as twenty minutes per plate.  Perhaps appropriately, given that Charcot’s posthumous critics…viewed his clinical demonstrations as fraudulent, the “objective” photographs that recorded the pathologies were themselves necessarily staged, posed, and manufactured constructions whose status as “facts” is as slippery as the live demonstrations they purport to record.

Charcot was not alone in exploiting his patients, in treating them as so many specimens rather than as suffering human beings.  The disdain and the callousness were a feature of the whole clinico-pathological tradition, something that American medical students visiting Paris for instruction viewed with dismay as early as the 1830s.  As feminist historians focused their attentions on hysteria as a female complaint, and perhaps the product, as some them speculated, of an inchoate, inarticulate protest against the roles in which Victorian women were imprisoned, Charcot’s serial exploitations of these poor creatures, his willingness to expose them repeatedly to the prurient gaze of his audience at whatever cost to their emotional well-being drew fierce criticism and reproof.  But those same moral failings were visible to Charcot’s contemporaries, and were the subject of bitter commentary, even from the literary figures such as Tolstoy and de Maupassant.  A Madame Renooz, in the pages of the Revue scientifique des femmes, protested about his “sort of vivisection of women under the pretext of studying a disease for which he knows neither the cause nor the treatment.”…

…And yet Charcot, as the feminist historian Elaine Showalter acknowledges, cannot be easily typecast as a crude misogynist, for he adopted liberal positions by the standards of his time on women’s rights, and his students and externs included women training for the medical profession.  Moreover, one of Charcot’s more striking departures from the conventional wisdom of his time had been his insistence that hysteria was not just a female disease…

Mark Jackson is Professor of the History of Medicine and Director of the Centre for Medical History at the University of Exeter. His newest work, Asthma: The Biography, is a volume in our series Biographies of Disease which we will be looking at for the next few week (read previous posts in this series here).  Each volume in the series tells the story of a disease in its historical and cultural context – the varying attitudes of society to its sufferers, the growing understanding of its causes, and the changing approaches to its treatment. In the excerpt below Jackson relays the story of Carlill v. Carbolic Smoke Ball Company.

On 7 December 1889, an American inventor, Frederick Augustus Roe, obtained a patent for a device that was designed both to cure and to prevent not only the deadly strain of influenza that was sweeping across Europe from Russia, but also a wide range of other respiratory complaints, including catarrh, bronchitis, coughs and colds, croup, whooping cough, hay fever and asthma. Sold from offices in Hanover Square in London for ten shillings, the Carbolic Smoke Ball comprised a hollow ball of India rubber containing carbolic acid powder. When the ball was compressed, a cloud of particles was forced through a fine muslin or silk diaphragm to be inhaled by the consumer. Boosted by testimonials from satisfied customers and endorsements from prominent doctors, Roe was sufficiently confident that the contraption would prevent influenza that, in several advertisements placed in the Illustrated London News and the Paul Mall Gazette during the winter of 1891, he offered to pay £100 to any person who contracted influenza ‘after having used the ball 3 times daily for two weeks according to the printed descriptions supplied with each ball’. As if to demonstrate the sincerity of his offer, Roe claimed to have deposited £1,000 with the Alliance Bank in Regent Street.

In November 1891, Louisa Elizabeth Carlill, the wife of a lawyer, purchased a Carbolic Smoke Ball in London and carefully followed the instructions for use. When Mrs Carlill contracted influenza the following January, her husband wrote to Roe claiming the ‘reward’ offered in the advertisements. Suggesting that the claim was fraudulent, Roe refused to pay and provided Mr Carlill with the names of his solicitors. In the resulting legal case, initially heard in the court of Queen’s Bench and subsequently reviewed by Appeal Court, the dispute did not revolve primarily around whether the plaintiff had used the device correctly or indeed whether or not she had contacted influenza; these issues were accepted largely as fact. Rather, legal arguments focused on whether the advertisement constituted a valid offer, rather than ‘a mere puff’, as Lord Justice Bowen neatly put it, and whether Mrs Carlill’s use of the smoke ball constituted acceptance of that offer. By deciding unanimously in Mrs Carlill’s favour, the English courts set a precedent regarding unilateral contracts that continued to inform the legal doctrines of offer and acceptance, consideration, misrepresentation, and wagering throughout the twentieth century.

While Carlill v. Carbolic Smoke Ball Company became a celebrated moment in legal history, it also reveals several dimensions of contemporary approaches to respiratory diseases, including asthma. In the first instance, it demonstrated the growing popularity of inhalation as a treatment. Ancient Greek, Egyptian, and Indian doctors had certainly recommended burning and inhaling smoke from a variety of plants to relieve asthma and catarrh, but this therapeutic approach blossomed from the mid-eighteenth century with the invention of several patent inhalers, such as those introduced in the 1760s and 1770s by the English physicians Philip Stern and John Mudge (1721-93). These devices allowed effective delivery of hot vapours from menthol, camphor, eucalyptus, and balsam directly to the lungs. Indeed, according to the author of a short tract entitled Instant Relief to the Asthmatic, published in 1774, the inhalation of medications for asthma was greatly superior to ‘inward applications’, which resulted in the drugs being ‘separated and subtilized by the body’ before reaching the lungs. In this instance, inhalation of vaporized acid salts, or ‘aetherial essence’, supposedly operated by loosening phlegm, increasing expectoration, and easing respiration.

Robert Tattersall is an internationally recognized authority on diabetes.  He received specialist training at King’s College Hospital, London and the University of Michigan in Ann Arbor.  He moved to Nottingham in 1975 where he became Professor of Clinical Diabetes.  His most recent book, Diabetes: The Biography, is part of the series Biographies of Disease which we will be looking at in the upcoming weeks.  Each volume in the series tells the story of a disease in its historical and cultural context – the varying attitudes of society to its sufferers, the growing understanding of its causes, and the changing approaches to its treatment.  In the excerpt below we learn about the discovery of insulin- a moment that changed the lives of diabetics forever.

After war service in Europe, Frederick Grant Banting (1891-1941) failed to get a surgical job at the prestigious Toronto Hospital for Sick Children and so set up as a doctor in London, Ontario. This was not a success, and to make ends meet he got a part-time job at the University of Toronto. In October 1920 he had to lecture the students on carbohydrate metabolism, about which he knew little. While preparing, he read an article about a man in whom a stone had blocked the pancreatic duct leading to atrophy of the digestive-enzyme-producing part of the gland but leaving the islets intact. This was hardly new, since it had been known for thirty years that this was what happened when the duct was tied in animals, but in his notebook Banting wrote:

Diabetus [sic]
Ligate pancreatic ducts of dog. Keeping dogs alive until ancini degenerate leaving Isletes.
Try to isolate the internal secretion of these to relieve glycosurea [sic]

Against the background of the fruitless attempts described in the previous chapter, it is not surprising that Macleod did not take Banting seriously. Macleod wrote: ‘I found that Dr Banting had only a superficial textbook knowledge of the work that had been done and no familiarity with the methods by which such a problem could be investigated in the laboratory.’ Quite apart from Banting’s ignorance, Macleod had lost interest in diabetes and was researching acid-base balance. Banting later said that during the first interview Macleod was so disinterested that he started reading letters on his desk. Nevertheless, he offered Banting a disused lab and two students, Charles Best (1899-1978) and Clark Noble (1900-78), who were to do alternate months. They tossed a coin to decide who should to the first month. Best ‘won’, but was so involved at the end of the first month that Noble agreed that he should continue.

Banting need an assistant, because he did not know how to measure blood sugar, and Macleod had wisely insisted on this as the end point of their experiments. During his research on the blood sugar of the turtle, Best had learned the new Lewis-Benedict method, which needed as little as 0.2 ml blood, whereas other methods needed 25 ml. Another stumbling block was that Banting had never done a pancreatectomy, an operation that at the time was used only in animal research. Macleod assisted at the first operation, but Banting and Best then worked alone, writing from time to time to Macleod, who replied with advice. In August 1921they depancreatized two dogs and treated one with pancreatic extract leaving the other as a control. The untreated dog died in four days which the treated one remained well. Macleod was encouraged by their results but felt that the falls in blood sugar might be due to dilution or even normal fluctuations. He suggested further experiments, to which Banting objected violently and accused Macleod of trying to steal their thunder. Nevertheless, the experiments were done. When Macleod returned in October, he had a stormy interview with Banting, who threatened to go elsewhere if better facilities were not provided. At a departmental meeting on 14 November 1921 Banting and Best gave a preliminary presentation of their work. One important suggestion at this meeting was that the best of showing that the extract worked would be if regular injections could prolong the life of diabetic dogs.

This was a logistic problem, because the duct-ligation method needed many dogs and a wait of seven weeks while the exocrine tissue degenerated. Banting’s solution was to use foetal calf pancreas, which Best got from the local abattoir. The rationale, as Sobolev had suggested twenty years before, was that it contained a high proportion of islets in relation to exocrine tissue. An important breakthrough came in December, when Banting decided to use alcohol in making extract (an idea Macleod had suggested some months before). It worked well and led them to wonder whether they could get a similar result with the more easily available adult beef pancreas. That they did must have been a surprise, because the original rationale for duct ligation was that the internal secretion would be destroyed by pancreatic enzymes. In fact, although Macleod and others believed this, it had been known since 1875 that fresh pancreas did not break down proteins. The intact gland contains an inactive precursor trypsinogen, which is converted into the protein-dissolving enzyme trypsin only by contact with duodenal juice. Around this time Banting and Best were joined by a biochemist, Bert Collip (1892-1965)-more accurately, he was foisted on them by Macleod, who regarded him as a proper scientist. Collip had come on a Rockefeller fellowship and was studying the effect of pH on blood sugar. Later he was asked to help with the purification of insulin and made rapid progress, although afterwards he downplayed his role, suggesting that any biochemist could have done the same.

Some time in December 1921 Collip began making extracts from whole pancreas and, at Macleods suggestion, tested them on rabbits. The extracts reduced the rabbit’s blood sugar, and how far it fell was a useful and cheap way of telling how potent the extract was.

The first use of insulin (an extract made by Charles Best) on a human being was on 11 January 1922. The pancreatic extracts were relatively impure, and the house physician at Toronto General Hospital described what he injected into the buttocks of 14-year-old Leonard Thompson as ‘15 cc of thick brown muck’. Thompson has been on the Allen diet since 1919 and weighed only 65 lb (29.5 kg). After the injection, his blood sugar fell from 440 to 320 mg/dl (24.4 to 18.3 mmol/l), but no clinical benefit was seen. The experiment was resumed on 23 January, when he was given Collip’s extract, and now his blood sugar fell during one day from 520 mg/dl (29 mmol/l) to 120 mg/dl (6.7 mmol/l). He continued treatment for ten days with marked clinical improvement and complete elimination of glucose and ketones from his urine. Subsequently he lived a relatively normal life, although reliant on insulin injections, before dying of pneumonia in 1935.

The first clinical results were published in the March 1922 Canadian Medical Association Journal, where the authors reported that they had treated seven cases…

Paolo Mazzarello graduated from medical school with honors from the University of Pavia, Italy, and earned a PhD in neurological sciences from the University of Milan.  He has since been a researcher for the National Research Council at the Institute of Molecular Genetics in Pavia, Italy and is currently Professor of History of Medicine at the University of Pavia, Italy.  His most recent book, Golgi: A Biography of the Founder of Modern Neuroscience, looks at an extraordinary intellectual who explored three major fields of biology and medicine, namely neuroscience, emerging cell biology, and the new science of medical microbiology.   In the excerpt below we learn a little bit about Golgi’s key discovery, the black reaction.

One winter day at the end of 1872, or the beginning of 1873, a scientist sat down to work at his microscope in the unlikely setting of an asylum for lunatics in northern Italy, after focusing back and forth for a while…

What a fantastic sight! On a yellow, completely transparent background, there appear sparsely scattered black fibers, smooth and small or thick and prickly, as well as black, triangular, star- or rod-shaped bodies!  Just like fine India ink drawings on transparent Japanese paper.  The scientist gazes upon it in astonishment.  He is more accustomed to the chaotic images produced by carminic acid and hematoxylin, which yield one dubious interpretation after another.  Here, on the other hand, everything is absolutely clear, without any possibility of confusion.  There is nothing more to interpret; one need only observe and note these cells, with their different, ramified extensions, like plants in the morning frost, covering an astonishingly large space in wavy lines; thse smooth and uniform extensions which, springing from the cell, cover great distances, before suddenly splitting up into a bunch of innumerable fibers…The delighted and astonished gaze cannot tear itself away from this fantastic sight.  Methodic wishful thinking has become reality.  Metal impregnation has produced a magnificent and unexpected slide.

This is how the renowned Spanish histologist Santiago Ramón y Cajal imagined the scene that, on that day, must have presented itself to the eyes of Camillo Golgi, the young chief physician of the Pie Case degli Incurabili (Charitable Home for Incurables) of Abbiategrasso.  This was the moment of the discovery of the “reazione nera” (black reaction), a revolutionary method for studying the structure of the nervous system.  This discovery contributed, more than thirty years later, to the awarding of the Nobel Prize for Medicine to Golgi.

For every student of medicine or biology, the name Golgi is synonymous with one of the basic structures in the cell: the Golgi Apparatus or Golgi Complex.  But this is only one of the many discoveries and achievements, particularly in the neurosciences, for which Golgi’s name deserves to be known by a much wider public than just devotees of biomedical sciences.  Unfortunately, his scientific fame lags far behind the historical significance of his discoveries.  The historical-critical literature on Golgi is scanty and the appraisal of his scientific work has been negatively affected by his rejection of the theory of the neuron and by the erroneous idea that his discovery of the black reaction was the result of pure chance.

The theory of the neuron, which was definitively confirmed only after the advent of the electron microscope, is an important example of a revolutionary conceptual transformation in biology. Using the terminology of Thomas S. Kuhn, without necessarily adopting his ideas on the evolution of scientific thought, the theory of the neuron represents a fundamental “paradigm” of the neurosciences in the same sense that atomic-molecular interpretation of matter or the theory of the discrete transmission of hereditary characteristics constitute fundamental paradigms of chemistry and genetics, respectively.  This concept of the neuron (and particularly that of synapses), by virtue of its being the elemental unit of modulation and transmission of information, has also assumed a preeminent role in many disciplines associated with the neurosciences such as informatics and artificial intelligence.  The multidisciplinary significance of the theory of the neuron does not simply represent an automatic extension to the nervous system of the principles of cellular theory, just as quantum mechanics is not simply a consequences of applying classical mechanics to subatomic structures.  Given the biophysical characteristics of neurons, the laws of their reciprocal communication, the complexity of their connections, and the extraordinary nature of the activities to which they give rise, it is evident how this theory constitutes the basis of a new segment of the scientific research that integrates “polyphonically” contributions from physics, electrochemistry, informatics, and clinical medicine, and in addition classical physiology and anatomy-histology.  From this perspective, the theory must be considered one of the great intellectual conquests of the nineteenth century.

To the end of his life Gogli remained a fiery opponent of this theory, despite having contributed materially its formulation, as he recognized explicitly in his Nobel Prize acceptance speech.  The technical histological revolution that he developed, the black reaction (known also as Golgi’s Method or chrome-silver reaction), which allowed the detailed investigation of the morphology of neurons and the basic architecture of cerebral tissue, was in fact the fundamental prerequisite that made possible the “paradigmatic” generalization of the theory of the neuron.

Often in the history of biology (and even more so in scientific discoveries generally), the introduction of a new technique revolutionizes a whole area of research, radically transforming preexisting disciplines and creating others from scratch.  One is reminded of the effect that monoclonal antibodies had on immunology and other branches of biology, or of the impact that the technology of recombinant DNA had on genetics.  The black reaction represented, for the histology  of the nervous system, a breakthrough of comparable importance, permitting the development of neuroanatomy as an autonomous discipline, and thus contributing to the birth of modern neuroscience.  Only after the introduction of Golgi’s Method, and the extraordinary structural descriptions of the nervous tissues obtained with it, did morphological investigations begin to be connected to physiological and functional investigations…

by Cassie, Associate Publicist

Michael B. A. Oldstone is a Member (Professor) at the Scripps Research Institute, where he directs a laboratory of viral immunobiology. He is also the author of Viruses, Plagues, and History: Past, Present, and Future, a look at viruses from smallpox to ebola to West Nile to the flu. In this excerpt, Oldstone explains how pigs, dogs, and ferrets help scientists discover that the flu was a virus, not bacteria.

Although suspected influenza epidemics occurred during several decades of the 1700s, Robert Johnson, a physician from Philadelphia, is generally credited with the first description of influenza during the 1793 epidemic. With his description available and improved public health statistics, epidemics were documented in 1833, 1837, 1847, 1889–90, and 1918.

However, the identity of the infectious agent that caused influenza remained debatable. In Germany, Richard Pfeiffer discovered “bacteria” present in great numbers in the throats and lungs of patients with influenza. Because of this agent’s large size, it could not pass through a Pasteur-Chamberland-type filter, causing many observers to speculate that influenza originated from a bacterium and not a virus.

Only by serendipity was the true nature of influenza as a virus discovered. This is a tale of pigs, hounds, foxes, and ferrets—all of which played decisive roles in the determination that influenza was a virus…

The story begins with J. S. Koen of Fort Dodge, Iowa, an inspector for the U.S. Bureau of Animal Husbandry. In 1918, he observed in pigs a disease that resembled the raging human influenza plague of 1918–19:

Last fall and winter we were confronted with a new condition, if not a new disease. I believe I have as much to support this diagnosis in pigs as the physicians have to support a similar diagnosis in man. The similarity of the epidemic among people and the epidemic among pigs was so close, the reports so frequent, that an outbreak in the family would be followed immediately by an outbreak among the hogs, and vice versa, as to present a most striking coincidence if not suggesting a close relation between the two conditions. It looked like “flu,” and until proved it was not “flu,” I shall stand by that diagnosis.

Koen’s views were decidedly unpopular, especially among farmers raising pigs, who feared that customers would be put off from eating pork if such an association were made. Ten years later, in 1928, a group of research veterinarians in the U.S. Bureau of Animal Husbandry, led by C. N. McBryde, reported the successful transmission of influenza infection from pig to pig by taking mucus and tissue from the respiratory tracts of sick pigs and placing it into the noses of healthy pigs. However, these investigators were unable to transmit the disease after passing the material through a Pasteur-Chamberland-type filter. Therefore, no evidence was yet available that a virus caused influenza. That situation changed when Richard Shope, working at the Rockefeller Institute of Comparative Pathology at Princeton, New Jersey, repeated McBryde’s experiments within a year of the negative report. By reproducing influenza disease in healthy pigs after inoculating them with material taken from sick pigs and passed through the Pasteur-Chamberland filter, Shope provided the first evidence that viruses transmitted influenza of swine.

…Initially, dogs were used for research on the [canine distemper] virus and for studies to develop the vaccine, but problems soon surfaced. Among the difficulties was the issue that some dogs had become immune because of a previous encounter with canine distemper virus so did not contract the disease when exposed; additionally, antivivisectionists and some pet owners objected to using “man’s best friend” as a research tool. These problems vanished when ferrets were substituted for dogs. Hound keepers on the English country estates had noticed that ferrets also developed distemper, presumably transmitted from dogs. Soon ferrets replaced dogs in canine distemper studies at both the Wellcome and the MRC laboratories.

In 1933, the first epidemic of influenza since 1919 struck London and, as before, spread quickly. Among the many humans infected were several members of the research staff at Wellcome and MRC laboratories. However, unexpectedly, ferrets kept at the Wellcome laboratory also became ill, with symptoms of wheezing, sneezing, and coughing reminiscent of human influenza infection. When Wilson Smith, a senior researcher at the MRC unit, recognized the situation, he infected ferrets with nasal washings from influenza-infected patients. As the ferrets came down with the influenza-like syndrome, both Smith and Christopher Andrewes examined them. A story soon told was that a sick ferret sneezed in Christopher Andrewes’ face. A few days later, Andrewes came down with influenza. Smith obtained washings from Andrewes’s throat, passed the material through a Pasteur-Chamberland-like filter, then injected the filtrate into healthy ferrets. Soon they too began sneezing and coughing, discharging phlegm from the nose and eyes and spiking a temperature. Here was the first evidence that a virus caused human influenza, at the same time fulfilling Koch’s postulates.

Following his studies with tuberculosis, Robert Koch formalized the criteria eventually called Koch’s postulates to distinguish a microbe causing disease from one that is a happenstance passenger. According to the postulates, a link between agent and disease is valid when the organism is regularly found in the lesions of the disease; the organism can be isolated in pure culture on artificial media; inoculation of this culture produces a similar disease in experimental animals, and the organism can be recovered from the lesions in these animals. These postulates require modification for viruses, however, because they cannot be grown on artificial media (viruses require living cells for their replication), and some are pathogenic only for humans. Nevertheless, these experiments with ferrets, humans, and influenza virus filled the bill for a modified Koch’s postulate. Considering the role serendipity played in the use of ferrets and the initial isolation of human influenza virus, one agrees with Pasteur: “Chance favors the prepared mind.”

Frederick Grinnell is Professor of Cell Biology and founder of the Program in Ethics in Science and Medicine at the University of Texas Southwestern Medical Center, Dallas. His newest book, Everyday Practice of Science: Where Intuition and Passion Meet Objectivity and Logic offers an insider’s view of real-life scientific practice. Grinnell demystifies the textbook model of a linear “scientific method,” suggesting instead a contextual understanding of science. Scientists do not work in objective isolation, he argues, but are motivated by interest and passions.  In the article below he looks at a recent article in Nature about defining death.  Read previous posts by Grinnell here and visit his website here.

An editorial in Nature (1 October, 2009) entitled “Delimiting death” supports the proposal to reconsider the legal definition of death. “Ideally,” writes the Nature editor, “the law should be changed to describe more accurately and honestly the way that death is determined in clinical practice.” The current definition uses the criteria: (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem. However, assessing ‘irreversible’, ‘all functions’ and ‘entire brain’ becomes to some degree a matter of physician judgment. In cases involving organ procurement for transplantation, the physician is under pressure to obtain donor organs that are as fresh as possible. The situation becomes conflicted. “Physicians know that when they declare that someone on life support is dead, they are usually obeying the spirit, but not the letter, of this law. And many are feeling increasingly uncomfortable about it.”

The Nature piece might be dismissed as adding nothing new to the discussion except for the provocative, two part, conceptual definition of death that the editor proposes: (1) “the person is no longer there” and (2) “can never be made to return.” The first part of this definition helps makes clear the symmetry between the most contentious issues of modern bioethics – endings and beginnings of life. The person is no longer there; we can harvest the body for organs. The person is not yet there; we can harvest the body (embryo) for stem cells.

Franz Rosenzweig’s metaphorical description of death — “His I would be only an It if it were to die.” –no longer is just a metaphor. The meaning of human death emerges according to the organization of human life. For a newly formed embryo, death means loss of viability of a single cell. After several cell divisions, loss of viability of a single cell no longer equals death. Rather, death becomes equivalent to development arrest. After 3-4 months of gestation, once the cardiovascular system develops, it becomes reasonable to speak of cardiovascular death. After 6-7 months, once the central nervous system develops, it becomes reasonable to speak of brain death. After development of modern life support systems, once machines can replace heart and brain functions, it becomes reasonable to speak of the person and the body as separated entities. Modern medical technology has succeeded in separating the I from the “living” It. Modern social thinking remains conflicted about accepting this separation.

Using Nature’s conceptual definition of death as a point of departure is unlikely to produce a more easily implemented legal definition of death for two reasons. First, nobody knows the answer to the question “Where is the person?” Indeed, trying to answer this question has become the central focus of cognitive neuroscience research with no consensus in sight except that – which would return us to the current definition of death — the person will be gone after cessation of brain function. Those who support using human embryos for research up to 14 days of embryo life select 14 days not because they know when the person has arrived but rather because they agree that before day 14 the person could not yet have arrived. Second, both from technical and practical points of view, the statement “can never be made to return” will add the word ‘never’ to the ambiguous list of other terms, i.e., irreversible, all functions and entire brain, about which the Nature editor complains. Therefore, given the inherent ambiguity, trying to decide the moment of an organ donor’s death with certainty will continue to have the potential to create a conflicted (or so it might feel) situation of choosing to sacrifice one life to save another. Clinical judgment still will be required as always is the case in the practice of clinical medicine.

If changing the legal definition of death cannot solve the practical problem, is there an alternative? One approach might be to change the informed consent process so as to involve organ donors more explicitly in the choosing process. Some donors will want to gift their organs only after certainty of death. Their wishes oblige physicians to act cautiously in declaring death, even if it means potentially reducing the value of the organs. However, other donors might view themselves as more involved participants whose advanced directives encourage their physicians to act to maintain the value of their organs, even if doing so means instructing the physician to obey the spirit and not necessarily the letter of the law. Instead of deriving a new definition of life’s end as proposed by the Nature editorial, we should aim for better public understanding of how modern medical technology has made defining life’s end so difficult.

Joanna, Intern

In The Thought that Counts: A Firsthand Account of One Teenager’s Experience with Obsessive-Compulsive Disorder, Jared Douglas Kant tells the story of how he was diagnosed with OCD at the age of 11 and dealt with the disease as an adolescent. Kant is a Clinical Research Assistant at the Massachusetts General Hospital Obsessive-Compulsive Disorder Clinic and Research Unit. Written alongside psychologist Martin Franklin Ph.D., Associate Professor of Clinical Psychology in Psychiatry, Department of Psychiatry, University of Pennsylvania School of Medicine, & Clinical Director, Center for the Treatment and Study of Anxiety, and science writer Linda Wasmer Andrews, a freelance health and psychology writer, The Thought that Counts serves as a guide for teenagers struggling with OCD and is part of the Adolescent Mental Health Initiative series created through a partnership with The Annenberg Foundation Trust at Sunnylands. In the following excerpt, Kant describes his new understanding of obsession in light of his struggles with OCD.

When I was younger, the word “obsession” made me think of infatuation. If a boy fell head over heels for a girl, spending an extraordinary amount of time and energy daydreaming about her and hanging on her every word, people would say, “He’s obsessed with that girl.” Naturally, it didn’t occur to me to use the same word to describe the peculiar thoughts I was having. But as I later realized, there’s a big difference between the everyday meaning of obsession and the scientific definition.

In scientific terms, an obsession is a recurring thought or mental image that seems intrusive and inappropriate, and that causes anxiety and distress. It’s different from simply being preoccupied with a cute classmate or a favorite hobby, because even after obsessive thoughts start causing serious problems, the person feels powerless to stop thinking them. At some point, the person realizes that the thoughts are controlling him or her instead of the other way around.

Obsessive thoughts aren’t just exaggerated worries about real-life concerns. Instead, they’re overblown fears and anxieties with little basis in reality. Yet once these thoughts push their way into someone’s mind, they refuse to leave no matter how hard the person tries to push them out.

Consider my obsession with images of disease, for instance. Flipping through magazines as a boy, I sometimes came across disturbing images of plague and pestilence, such as flies buzzing over open sores. When I saw such pictures, I carefully avoided touching them. Occasionally, though, I would make a mistake. My finger would drag across the ink on the page until it hit one of the infected people. Whenever this happened, I screamed inside. I ran to the bathroom, slathered myself in soap, and turned the hot water up to boil. I was steaming, and I must have looked like a lobster by the time I emerged from the bathroom.

My reaction to touching the images illustrates another critical point: Obsessive thoughts lead to intense anxiety about something bad or harmful that the person fears will occur. The anxiety is so strong that the person feels compelled to do something – anything – to get relief and ward off the feared consequence. That’s how compulsions, such as my excessive hand-washing, are born. From a scientific standpoint, then, a compulsion is a repeated act, either behavioral or mental, that a person feels driven to perform in response to an obsession, to keep something bad from happening or to reduce the associated distress.

William R. Clark is Professor and Chair Emeritus of Immunology at the University of California, Los Angeles.  His new book, Bracing For Armageddon?: The Science and Politics of Bioterrorism in America, provides a reassuring overview of what we really need to worry about – and what we don’t.  In the excerpt below we learn about one early bioterrorism attack in America.

In 1981, the Rajneesh cult, founded by a displaced Indian mystic named Bhagwan Shree Rajneesh, purchased a 60,000-plus-acre ranch in north central Oregon, not far from the city of The Dalles (population 11,000).  The Rajneesh commune soon grew to several thousand souls, who enjoyed various degrees of success in their search for peace and enlightenment, in an atmosphere of easy drugs and sex.  But the Bhagwan clearly flourished.  He accumulated ninety Rolls Royces, five private jets, and a helicopter.

Not content with having built a thriving community on their own land, cult members gained electoral control of the nearby small (population 75) town of Antelope in Wasco County.  They named their new town Rajneesh and quickly converted it to their own needs and ends, to the utter disgust of the mostly retired locals.  Soon, perhaps growing weary of life in such a small town, Rajneeshees began vying for seats on Wasco County boards and commissions.  Reaction at the county level was mixed, but mostly negative.  A few saw potential downstream benefits from the influx of money and reasonably educated people, but most shared the views of their compatriots in Antelope.

In mid-September 1984, a dozen people who worked in or had recently eaten in several restaurants in The Dalles became ill from food poisoning.  One of the restaurants, a Shakey’s Pizza franchise, was co-owned by a member of the Wasco County land-use board, but this raised no particular flags at the time.  The number of victims grew over the following week, and the biological culprit behind it was soon identified by public health officials: Salmonella enterica typhimurium, a bacterium commonly causing food poisoning.  Everyone was treated with appropriate antibiotics, no one died, and the incident seemed to have subsided.

But a week later it was back.  This time ten restaurants were involved.  Local health services, including medical laboratories, were overwhelmed.  The only hospital in The Dalles quickly ran out of beds.  The number of persons who became ill soon exceeded 700, considerably beyond what might be expected in a community of this size for a normal outbreak of salmonella poisoning.  The city called the Centers for Disease Control and Prevention (the CDC) in Atlanta for help.  By the time help arrived, local health officials determined that most or all of the affected people had eaten at salad bars, and restaurants were immediately advised to stop serving salad.  They did.

There followed an exhaustive investigation of all suppliers of salad vegetables and dressings to local restaurants.  Everything came up clean; even the local water.  Preliminary reports from state and federal health investigators stated that the poisonings were most likely caused by accidental incursions of salmonella into the food supply of the restaurants involved.  Even the CDC felt that the food handlers were the most likely source for introduction of the bacteria into the salad bars.  Some locals, in particular another member of the Wasco County land committee, believed the Rajneesh cult was somehow involved, but lacking any hard evidence or direction from health authorities, investigations into this possibility eventually fizzled out.

The involvement of the Rajneeshees became clear only as the result, a year or so later, of internal squabbles within the cult. The Bhagwan himself implicated some of his lieutenants in the affair, and called for a government investigation, after which he beat a hasty retreat to India.  Authorities found abundant evidence at the commune of not only S. enterica typhimurium but a fairly sophisticated medical research laboratory and evidence that the cult had considered employing other deadly pathogens, including HIV – the AIDS virus.  They had purchased salmonella essentially over the counter, from a Seattle scientific supply house.  Among their intended victims, in addition to various county officials, was U.S. Attorney Charles Turner, the top federal prosecutor in Oregon.  He was to be spared infection with salmonella.  Cult members planned to shoot him.  They failed.  But they also intended to use their cultured salmonella to poison the Dalles water supply in the days before an upcoming election.  The grand plan, as it turned out, was to reduce the number of Wasco County citizens able to vote, thereby increasing the influence of Rajneeshees.  For various reasons, this never came about.

Probably no more than a dozen Rajneeshee leaders were fully aware of our involved in the salmonella poisonings.  Seven cult members were ultimately indicted in various murder or attempted conspiracies.  The cases against the conspirators came to a close only in 2005, when the last of these returned from self-imposed exile in Germany and surrendered to authorities.

While the Rajneesh incident gained national and international attention among those who had been predicting bioterrorism in America, it could be argued that what happened in Oregon was not so much a form of bioterrorism as a simple criminal attempt to manipulate a specific civilian population and its various civil agencies through malicious intimidation – a biocrime.  There was no discernible political aim beyond an attempt by a few members to influence a single election and to expand their power and influence within the cult, and perhaps the intimidation or possible elimination of some individuals.  Still, many of the features of bioterrorism were there: preparation and crude weaponization of a human pathogen, delivery of the pathogen to intended victims, and serious social and psychological disruptions in the targeted population.

The AMA Manual of Style is the ultimate go to resource for writing articles as well as understanding ethical standards in medical and scientific publishing, and it is now available online.  In the article below, Phil Sefton, ELS, Senior Manuscript Editor at JAMA and a contributor to www.amamanualofstyle.com, weighs in on “nauseating” vs. “nauseous.” This article first appeared on the AMA Manual of Style site.

Writers and editors rushing to meet deadlines know the feeling. The effects of stress, a few too many cups of coffee, and perhaps a candy bar or bag of chips in place of a meal can conspire to make the most steely-nerved wordsmith feel a tad nauseated. Or is it nauseous? And what of that stress, that coffee, that ill-chosen meal replacement—are its effects nauseating or nauseous?

Grammarians with more prescriptive leanings (ie, those concerned with language as it “should” be used, which presumably would include most writers and editors) would say that a person feels nauseated and that which has made him or her feel that way is nauseous. Those with more descriptive leanings (those concerned with language as it is actually used, which includes professional linguists as well as armchair observers of language) are eager to point out that while nauseated is still more often used to mean feeling the effects of nausea, the use of nauseous in that subjective sense is rapidly gaining acceptance. Similarly, while nauseous is still more often used to mean causing nausea, the use of nauseating in that causative sense will soon be more prevalent, if it is not already. Debates on the merits of prescriptive vs descriptive use of these terms can be quite heated, and current dictionaries and usage guides often attempt to walk a line between the two camps—which, considering the potential for rancor, is probably not a bad idea, particularly taking into account the ever-evolving nature of language as well as the history of these terms.

So first, a little history. Despite the pronouncements of some prescriptive grammarians promoting the idea that nauseous, when used to mean “feeling the effects of nausea,” is yet another example of a weed newly sprung up in the garden of educated usage, it appears that the term was used in that sense as early as 1604. What is more, it was likely not used to mean “causing nausea” until 1612 or later. At some point, the rule was set forth dictating that nauseous should be used to indicate causing nausea and nauseated to indicate the subjective feeling of nausea—a rule that for the most part held sway until the mid-20th century, when nauseous once again began to be used by persons describing how they feel.

Nauseous, then, when used to describe the feeling of nausea, is something of a grammatical atavism, a throwback to an earlier usage that seems to have fallen into disfavor in the intervening centuries. The term has regained its original meaning in a few generations, a resurrection only accelerated by today’s fast-paced media mix. For example, when comedian Mike Myers’ Saturday Night Live character, Linda Richman, claimed that something “makes me nauseous” (always pronounced as two syllables, with the slightest of pauses when pronouncing the first: “naaw′ shus”), the use of the term in that sense gathered steam in short order, gaining an ever-widening circulation as viewers of the program used it in conversation and e-mails; it likely now lives a healthy and happy life in the various social networking media. Other related terms from the 17th century—nauseation, nauseative, nauseity, nausity—are now obsolete or used very rarely, but for now nauseous as used to describe the subjective state of nausea seems here to stay.

So how does all of this pan out for the person seeking guidance on the use of nauseous, nauseated, and nauseating? As is often the case, an answer—very seldom is there such a thing as the answer—lies in the ever-shifting borders between the spoken and the written word. Whereas the use of nauseous in the subjective sense when speaking now seems a given, nauseated is still holding its own in text. Conversely, the use of nauseous to indicate the cause of nausea is rapidly falling into disuse in spoken conversation (and when it is used, it is sometimes confused with noxious), whereas it maintains only a rapidly diminishing tenuous lead over nauseating in text.

Accordingly, JAMA and the Archives Journals very seldom use nauseous in the causative sense and not at all in the subjective sense (unless part of quoted material); nauseating is used for the former and nauseated for the latter, at least until the dust has settled on another generation or two of language evolution. In the meantime, writers and editors rushing to meet deadlines are encouraged to take steps to eliminate or reduce stress, consume coffee in moderation, and make prudent dietary choices if skipping meals.

Robert Veatch is Professor of Medical Ethics at the Kennedy Institute of Ethics, Georgetown University. He received the career distinguished achievement award from Georgetown University in 2005 and has received honorary doctorates from Creighton and Union College. His new book, Patient, Heal Thyself: How the “New Medicine” Puts the Patient in Charge, he sheds light on a fundamental change sweeping through the American health care system, a change that puts the patient in charge of treatment to an unprecedented extent. In the original article below, Veatch looks at how the empowerment effected Michael Jackson’s medical decisions and the responsibility of his doctor.

Dr. Conrad Murray is the doctor who apparently administered a fatal dose of the anesthetic, propofol, to Michael Jackson in a desperate attempt to respond to his cries for help in getting some sleep. He has received rough treatment from the media. Jackson’s death has been ruled a homicide and the media are reporting that he will be charged with manslaughter. I think that judgment is too quick and want to come to the doctor’s defense.

The case is, of course, being tried in the press before we have all the details, but the likely scenario is emerging. Making some plausible assumptions, I think a case can be made for the doctor’s decisions. Let me assume, for purposes of discussion, that the doctor did not intend to kill Michael (He was reportedly being paid $150,000 a month to be Michael’s full time physician. Even if he had completely abandoned his duty to serve the patient, he would be a fool to intend the death.) Let me assume that the lethal effects were foreseeable, but not inevitable side effects of a very potent drug. Let me also assume that Michael had been informed by Dr. Murray how dangerous the drug was and how unusual it was to use it for this purpose. Possibly, he had even told Michael that the drug’s labeling did not include the use of propofol outside of a hospital and that almost all physicians would refuse to use it this way.

With these assumptions, a prosecutor will have a difficult time accusing the doctor of a crime. It is not even clear to me that “homicide” is the right term for the death. First, it is important to realize that “off-label” uses of drugs by doctors is not illegal. It is done all the time when a physician becomes convinced that it in the patient’s interest. Second, it is critical to understand that medical choices about what is in a patient’s interest are directly dependent on the patient’s goals and values. They cannot simply be read out of a textbook as if medical science can prove what is in a particular patient’s interest. (Think about whether aggressive chemotherapy is in a terminal cancer patient’s interest or whether an abortion is in the interest of a pregnant woman.) The patient’s interest is necessarily a subjective matter about which only the patient can have direct knowledge.

It seems clear that Michael was in the advanced stages of insomnia and was in excruciating agony from persistent lack of sleep. That is an awful situation about which patients often have to make desperate choices. None of us can know what was in Michael’s head that caused the insomnia or led him to plea for pharmacological intervention. We do know that other drugs had been used even that fateful night (benzodiazepines that are often used to reduce anxiety and induce sleep). These other drugs had failed to solve the problem and made the use of the propofol even more dangerous, something Dr. Murray surely knew and presumably had told Michael.

Now the question for Dr. Murray and for Michael Jackson is, given his desperate situation, is the only drug that will give him some sleep worth the very great risk of side effects, even death? Surely, for most of us the answer would be negative, but that doesn’t mean it was Michael’s answer. Given that he had apparently received the drug many previous times without side effects, I don’t see how we can claim that Michael would be wrong to decide that the risk would be worth it in his case. Deciding whether the drug is “worth it” is a value judgment, not a scientific fact that the doctor can look up in a book. Even if almost everyone else would have decided not to try the desperate off-label use, I don’t know how we can say Michael’s gamble was wrong for him.

But, you might say, even if Michael’s judgment was understandable, surely Dr. Murray was wrong to go along with his patient’s demand. Surely, other physicians would not have agreed. A physician is supposed to be a responsible professional who has the right not to go along with a patient’s very unusual and risky demand. Most physicians would have refused to provide the propofol (at least outside of a hospital) and that is understandable, but this does not prove that Michael’s value judgment about the risk was wrong or that Dr. Murray was wrong to comply. Some medical issues are appropriately judged by what is called a “standard of care.” The correctness of the physician’s behavior is judged by what his colleagues similarly situated would have done. This, however, is not a decision that should be judged by that standard. If it is possible that Michael had made a rationally defensible decision that the risk was worth it for him, then a physician is within his rights to decide to cooperate in a legal behavior if he so chooses. He surely would have had the right not to provide the dangerous drug for off-label use, but he also has the right to decide it is a tolerable risk. If he does so after the patient is adequately informed, I don’t see how we can fault him assuming that the lethal effect was not intended.

This turns out to be crucial for the rest of us if we are to get high-quality, rational medical care. We have for many years recognized that most powerful, valuable drugs have anticipated side effects. If we choose to take the risk and the side effect occurs, we don’t say that the choice was a mistake. If the side effect is death, we don’t say it was a homicide. Provided the intended beneficial effects are good enough, we say that the side effect is tolerable even if it is foreseen. That, in fact, is precisely the justification for doctors’ use of narcotics to control severe pain in cancer patients even though they know that the side effect can be respiratory depression and even death. Most ethical systems have long acknowledged that such “unintended, but foreseen” deaths are tolerable. Normally, such a death is not deemed a “homicide.” Just may be, if we put ourselves in Michael’s shoes and plug in the value judgments he made, we can understand why Dr. Murray, apparently with great reluctance, was willing to go along. I can’t fault him if that was what he did.