The novel follows Martin Arrowsmith from a small Midwestern town to the upper reaches of American research science. As a boy in Elk Mills he reads anatomy in the town doctor’s office, and at the University of Winnemac he falls under the spell of Max Gottlieb, a German bacteriologist who teaches him to distrust easy answers and love the laboratory above the clinic. Martin’s career moves quickly from medical practice into research as a vaccine discovery vaults him from a small-town practice into a prestigious New York institute, and finally to a Caribbean island where bubonic plague is raging. There he faces an ethical conundrum: whether to withhold his unproven cure from half the population to prove it works, or whether to save as many as he can without conclusive evidence. When his wife Leora dies in the experiment, Arrowsmith throws caution to the wind and immunizes everyone, sacrificing his chance at greatness. In the aftermath, he walks away from money, marriage, and fame to chase pure science in a rural cabin, leaving the reader to decide whether he’s really a hero or just a reclusive crank. 

Lewis wasn’t the first American writer to champion medical science. Willa Cather and Oliver Wendell Holmes laid some of this ground first. But biographer Mark Schorer isn’t wrong in saying that “Martin Arrowsmith was a new hero, scientific idealism a new subject, and scientific individualism a new (and rather unscientific) perspective.” And Lewis was probably the first American writer to coauthor a major novel with a scientist, the bacteriologist Paul de Kruif. 

Arrowsmith won the Pulitzer in 1926 (though Lewis refused to accept the award), and the novel was a major factor in the Swedish Academy’s decision to award Lewis the Nobel Prize in 1930. It represents a hard-fought accord between science and art that has vanished from the literary scene today. But it’s hardly a one-note celebration of science. Lewis suggests that once scientific medicine withdraws from public view, the ominous tropes of the nineteenth century may creep back in. 

Like most of Lewis’s novels,  Arrowsmith is filled with overwritten scenes and dialogue riddled with slang. But I’d be curious, if I could teach it to medical students today, how much of themselves they might see in the character of Martin Arrowsmith, a boy from flyover country who nearly rose to medical immortality but crashed, Icarus-like, on his own hubris. 

A Novelist and a Whistle-Blower 

Lewis was immersed in medical culture throughout his young life as the son of a rural physician, but he was not a scientist himself, and never aspired to a career in medicine. His father, Edwin J. Lewis, began his medical training at Rush Medical College in 1875, graduating two years later as an M.D. and eventually opening a small practice in Sauk Centre, Minnesota, where he advertised himself as a physician and surgeon. Memories of his father provided a general basis for the opening scenes of Arrowsmith, set in rural Winnemac (or Minnesota), but Lewis needed to grasp both the passion and methodology of real scientists to create his medical hero. 

Lewis met his coauthor, Paul de Kruif, at a meeting arranged by his publishers. De Kruif held a Ph.D. in bacteriology from the University of Michigan. He had also worked as a researcher at the Rockefeller Institute in New York, but had been fired after the director discovered that de Kruif had published an anonymous exposé of the Institute’s financial corruption and premature publication of scientific results. He was an ideal partner for Lewis, whose satires of the American Midwest elevated skepticism to an ethical ideal. As E. L. Doctorow observes, “Expecting his countrymen to be more than they were, looking for a resonant truth and righteousness, Lewis had found an American spiritual life that could elicit from him nothing more than bitter derision.” Lewis and De Kruif counterbalanced one another professionally, one steeped in medical science, the other in literary art, but they were both truth-seekers, through and through. 

De Kruif was professionally destitute when he met Lewis, having recently lost his position at the Rockefeller Institute. He had seriously jeopardized his chances of finding work in his field, as university bacteriology departments and pharmaceutical companies balked at hiring known whistle-blowers. He needed Lewis and the stimulus of a major literary project as much as the author needed his expertise. 

Lewis gave De Kruif “assignments” during their travels, such as writing a fictional biography of Gottlieb, Arrowsmith’s mentor. The apprenticeship would later pay off for De Kruif, who became a bestselling author of scientific history just one year after the publication of Arrowsmith. His book The Microbe Hunters, which sold over one hundred thousand copies in 1926, alone, was one of the major nonfiction books of the decade. 

Indeed, De Kruif learned literary craft so well that it’s impossible to know who wrote certain passages in  Arrowsmith. Take, for instance, the scene where Martin realizes that he is about to make a potentially groundbreaking scientific discovery about the behavior of bubonic plague. Late at night, alone at the McGurk Institute (the fictionalized Rockefeller Institute), Arrowsmith simply can’t wait to process his lab results: 

At a hectic run, not stopping for lights, bumping corners and sliding on the too perfect tile floor, he skidded down the stairs and galloped through the corridors to his room. […] 

Then he forgot…war, night, weariness, success, everything, as he charged into preparations for an experiment, his first great experiment. He paced furiously, rather dizzy. He shook himself into calmness and settled down at a table, among rings and spirals of cigarette smoke, to list on small sheets of paper all the possible causes of suicide in the bacteria. 

Lewis and De Kruif collaborated so intimately that the scientist began to write like the novelist and the novelist began to think like the scientist. They should have shared the honors that followed, but Lewis insisted on crediting De Kruif more as a fact checker than as his equal. 

Cruelty or Cure? 

It’s hard to imagine language like this from a doctor now, but Martin Arrowsmith dedicates himself to the search for “the Why that made everything so.” Impatient with memorizing facts, he “wanted to look behind details and impressive-sounding lists of technical terms for the causes of things, for general rules which might reduce the chaos of dissimilar and contradictory symptoms to the orderliness of chemistry.” Arrowsmith believes in precise technique, but he’s also emotionally invested in the work, demonstrating an almost fanatical belief in the scientific method. 

His defining characteristic is his curiosity, which helps him crack riddles others see as mere aberrations. Lewis writes, to this effect: 

Now in Martin Arrowsmith there were no decorative heroisms, no genius for amours, no exotic wit, no edifyingly borne misfortunes. He presented neither picturesque elegance nor a moral message. He was full of hasty faults and of perverse honesty; a young man often unkindly, often impolite. But he had one gift: curiosity whereby he saw nothing as ordinary. 

When he sees something weird in his test tubes, he says, “Now there was some cause for that, and I’m going to find out what it was.” This is how Arrowsmith discovers the X Principle. He tells his wife Leora that it could lead to the cure of every germ disease, which overstates the case, but it is a major scientific breakthrough—not only for Martin, but potentially for humankind. 

Arrowsmith’s X Principle is a remarkable development in the novel. Perhaps for the first time ever in American fiction, Lewis invites a reader to participate in the euphoria of scientific discovery, rooting for the medical scientist as he plugs away in the laboratory. Later he causes a stir among the farmers in Wheatsylvania, the little town where he briefly sets up a private practice, by curing a seemingly unstoppable blackleg epidemic with an original vaccine prepared in the makeshift laboratory at the back of his doctor’s office. The vaccine requires several experimental dry-runs, but Martin works on the project after hours, glad to be searching for the root cause—the Why—of the disease. 

Later, Arrowsmith travels to St. Hubert, a fictional Caribbean island, to test the X Principle on a population besieged by bubonic plague. Verifying the efficacy of his bacteriophage would require a control group, which would mean denying the remedy to a portion of the populace. Is it more compassionate to inoculate everyone with an unproven (but promising) remedy or to withhold treatment for conclusive proof, thereby guaranteeing the health of future generations? It’s an important ethical question, but one that politics ignores. It’s hard to name a doctor today who is both publicly promoting scientific knowledge and defending human rights in quite this way. 

Arrowsmith develops a high-stakes debate over humanitarianism. One doctor argues that temporary cruelty does not justify eventual compassion; accordingly, he refuses to receive the preventive bacteriophage inoculation until the entire population of St. Hubert has been immunized. Arrowsmith’s mentor, Gottlieb, insists that true humanitarianism requires establishing irrefutable scientific facts. Gottlieb corners Arrowsmith before he leaves for St. Hubert and delivers one of his longest speeches of the novel. The St. Hubert experiment is Martin’s chance to become a “Great Man,” and Gottlieb intensifies the pressure: 

Be sure you do not let anything, not even your own good kind heart, spoil your experiment at St. Hubert. I do not make funniness about humanitarianism as I used to […]. So many men, Martin, are kind and neighborly; so few have added to knowledge. You have the chance! You may be the man who ends all plague […]. 

You must not be just a good doctor at St. Hubert. You must pity, oh, so much the generation after generation yet to come that you can refuse to let yourself indulge in pity for the men you will see dying. 

As I write this,  doctors are taking to Instagram to protest insurance companies who deny patients coverage for life-saving procedures. We’re having a hard enough time helping people now; no one is talking about the generation after the generation yet to come. But this is what Lewis imagines in Arrowsmith’s unorthodox heroism: by withdrawing from society into the laboratory, as he does to prepare his blackleg serum or to discover the X Principle, Arrowsmith has a chance to become a legendary benefactor of public health. But is the greatest degree of human compassion possible only through momentary cruelty? 

Arrowsmith’s heroism might have been lost on the popular audience had Lewis seen the St. Hubert experiment through to the end. Instead, Lewis creates a strategic compromise. First, he sets up the conditions of the experiment, outlining arguments for and against denying the vaccine to portions of the St. Hubert population; this lends credibility to Martin Arrowsmith as a scientific physician by highlighting the complexity of his choice. Then Lewis derails the experiment with the accidental death of Arrowsmith’s wife Leora, who dies suddenly of plague. Stricken with grief and guilt (because he had been entertaining adulterous thoughts at the time of her death), Martin begins administering his serum indiscriminately to the people of the island, compromising the scientific integrity of his results, but demonstrating his capacity for emotion. 

After Leora’s death, he returns to the self-destructive behavior of his vagrancy during medical school, drinking heavily and acting as if he no longer cares about knowledge or the accompanying reward of fame. Lewis writes: “[…] all day, Martin injected a line of frightened citizens, in the Surgeon General’s office,” during which time he “had a bitter satisfaction in throwing away all his significance, in helping to wreck his own purposes.” In the end, no one knows whether the plague disappears from St. Hubert as a result of “phage or rat-killing or Providence.” The result is tragic by Gottlieb’s standards, but it further endears Arrowsmith to readers, whom Lewis manages to educate about the ethical quandaries of research science while introducing the research scientist, himself, as a man of passion and human weakness. 

Arrowsmith loses his chance to enter the historical record alongside scientific greats such as Pasteur, but Lewis reinforces his heroic stature on the human level. Alongside characters like Hawthorne’s Rappaccini who becomes so obsessed with science that he forgets humanity, Arrowsmith’s capacity for emotion in the heat of his greatest experiment is extraordinary. In fact, I’d like a little more evidence that grief, for today’s doctors, is as powerful as scientific curiosity, profit, or personal branding. We could use more reminders that science happens in social contexts and that it is vulnerable to the weaknesses and biases of those who do it and the systems that support it. 

A Flawed Hero 

Arrowsmith is a bildungsroman—the first to show how an ordinary person becomes a scientific hero—but it borrows from other literary forms, such as the epic and the portrait of the artist. 

Martin is raised in a small town called Elk Mills, where he is the “unofficial” assistant to Doc Vickerson, the self-styled “plug doc” and alcoholic who has managed to compile the first museum of natural history in the county. In a drunken speech, Vickerson tells the young Arrowsmith to get all the training he can in the sciences in order to realize his full potential as a physician. “Set a high goal,” he admonishes Martin. “Don’t let things slide. Get training. Go college before go medical school. Study. Chemistry. Latin. Knowledge!” A nice little pitch for the liberal arts, even if it sounds quaint to us now. 

The University of Winnemac is Arrowsmith’s portal to opportunity, where preparation for medical school consumes his life. His entire identity revolves around his education, where “the purpose of life was chemistry and physics and the prospect of biology next year.” Arrowsmith’s junior year of college is set in 1904, and the descriptions he hears of Gottlieb, his professor of bacteriology, reflect lingering stereotypes of the medical scientist as a rogue. Rumors about Gottlieb suggest that “he was doing terrifying and costly experiments which probably had something to do with human sacrifice. It was said that he could create life in the laboratory, that he could talk to the monkeys which he inoculated, that he had been driven out of Germany as a devil-worshiper or an anarchist.” 

Gottlieb, whose name translates literally from German as “Godlove” and more accurately as “Beloved God,” recalls the master-apprentice relationship typical of the bildungsroman through his mentorship. From his introduction in the Winnemac scenes, Gottlieb remains the dominant influence on his young protégé throughout the remainder of the novel. When Arrowsmith asks to be admitted into his course before having taken all of the prerequisites, Gottlieb says: 

There are two kinds of students the gods give me. One kind they dump on me like a bushel of potatoes. […] The other kind—they are very few!—wish a liddle [sic] bit to become scientists, to work with bugs and make mistakes. Those, ah, those, I seize them. I denounce them. I teach them right away the ultimate lesson of science, which is to wait and doubt. Of the potatoes, I demand nothing; of the foolish ones like you, who think I could teach them something, I demand everything. (11) 

He goes on to tell Arrowsmith that he must take physical chemistry before he will be ready for bacteriology; this is the difference between true scientists and imitators. Gottlieb’s first public experiment, an inoculation of guinea pigs with anthrax repulses many of Arrowsmith’s classmates, but the young Martin later imagines himself repeating experiment: “as he remembered Gottlieb’s unerring fingers, his hands curved in imitation.” 

But Arrowsmith needs flaws if he is to be taken seriously as a character, and he nearly destroys himself at several crucial moments in the narrative. The same restlessness that fires his curiosity is also his potential undoing—binge drinking makes him careless in the laboratory and lack of sleep makes him belligerent. When Gottlieb reprimands him for a series of avoidable errors, Arrowsmith’s defiant response nearly ends his medical career. The medical dean decides to suspend rather than expel him, and Martin is temporarily exiled from the University that has been the primary touchstone for his identity as a young adult. 

But Arrowsmith’s flaws show that the most promising benefactors of public health sometimes seem the most misanthropic by nature. For Lewis and De Kruif, two idealists who effectively replace religion with science, pure science requires complete devotion. This is a high standard that none of Lewis’s characters fully attains; it’s in their failings that he endears them to readers, unveiling the joys and heartaches of a scientist, making the doctor’s emotional life known. 

Back to the Lab, Out of the World 

If the novel were to end in St. Hubert with Martin Arrowsmith doling out medicine to everyone in sight, it might be a story about compassion defeating cold-hearted science. Leora would be a martyr and Martin would be a widower, unselfishly serving humanity. But the story doesn’t end there: Martin marries Joyce Lanyon, a wealthy woman from New York, and briefly celebrates the birth of a son before divorcing Joyce, abandoning his son, and withdrawing to a remote cabin to dedicate his life to research. Arrowsmith is hard to like as a deadbeat father and cultural isolationist. Why, after taking such pains to help us understand the beauty and importance of science through Arrowsmith’s life, would Lewis turn his hero into such a miserable person? Is that really what science does to the heart? 

Lewis leaves us with a paradox. Nearly all of Arrowsmith’s flaws are scientific virtues: his brutal honesty, his distaste for wealth, his comfort with solitude. But  Arrowsmith’s  most troubling implication is that the medical scientist might give up trying to communicate with the public at all, choosing, instead, the uninterrupted calm of the laboratory, where discoveries happen unseen. When that happens, we’re thrown back to the distrust of the nineteenth century. Are the researchers devoted to unlocking the great Why beneath physical things today doing it for themselves or for humanity? Are they Arrowsmiths or Rappaccinis? 

The public story of medicine is a balancing act. It requires careful translation of facts into culture. It’s hard work, and it never ends. It’s much easier for suspicion to prevail. 

That’s why I see  Arrowsmith as a miracle. Think about what it took for that book to exist. It took a Paul de Kruif: a researcher with enough integrity to sacrifice financial gain for truth-telling. And it took a Sinclair Lewis: a kindred spirit who was willing to make an artist of a lab scientist. 

In Martin Arrowsmith, the scientific physician comes of age as a character, no longer a shadowy villain, but an artist in his own right: a figure whose potential for greatness or failure extends the medical narrative to the full scope of human experience. 

Web photo: Wiki Commons

The time has come when the existence of a private pestilence in the sphere of a single physician should be looked upon, not as a misfortune, but a crime; and in the knowledge of such occurrences the duties of the practitioner to his profession should give way to his paramount obligations to society.

— Oliver Wendell Holmes, “The Contagiousness of Puerperal Fever”

It would have been cold on February 13, 1843, when the Boston Society for Medical Improvement convened. But anyone who heard Oliver Wendell Holmes’s fiery speech about puerperal fever would have forgotten about the chill outside immediately.

Holmes stood just 5’ 3”. And he was young, only 34 years old. But he was hot with moral authority. He was so sure that puerperal fever was contagious that he accused his skeptical colleagues of murder. He knew that in order to make them listen, he had to do more than lay out the facts. He needed a persuasive story.

As I’ll show presently, it was precisely this approach that allowed Holmes to win Nathaniel Hawthorne’s trust as personal physician to the great author near the end of his life. No mean feat, since Hawthorne was terrified by medical science.

The Crowd Puller

In those days, you had to speak well publicly to make a name for yourself. Oratory was required in school. In New England, the rhetorical standard was set in the pulpit, and public discourse followed. So it wasn’t an insult if someone said your speaking or writing felt sermon-like. Good sermons could awaken, convict, inspire, and transform even the most uneducated souls. The best professors and the best doctors fit the ministerial mold.

In New England, good speakers were a dime a dozen. But Holmes stood alone.

One of Holmes’s students recalled how he could hold a crowd:

He always makes people attentive, and I have been told that there is no professor whom the students so much like to listen to. In one of his books he says that every one of us is three persons, and I think that if the statement is true in regard to ordinary men and women, Doctor Holmes himself is at least half a dozen persons. He lectures so well on anatomy that his students never suspect him to be a poet, and he writes verses so well that most people do not suspect him of being an authority among scientific men.

This was also a time when science was retreating from the public sphere. Hawthorne was writing short stories about the terrors of the lab, where Rappaccinis and Chillingworths played God. As Michel Foucault said, it was a time when some doctors took the patient into account “only to place him in parentheses.”

Holmes was a scientist, but he hated how science made some of his peers “think only in single file.” And so he tried to wake his colleagues up on that cold day in Boston with facts, but also with panache and metaphor.

The Case for Contagion

Attention spans were different in 1843. The full text of Holmes’s speech, which he later published in essay form, was over 12,000 words. It would have taken him at least an hour to deliver it. He had to review many cases in depth, not just spin fetching tales.

But that’s why everyone in the Boston Society had gathered that day. They wanted to get better as doctors, for medicine itself to improve. So they listened.

Holmes points out that William Dewees’s A Treatise on the Diseases of Females, published in Philadelphia in 1833, explicitly denies that puerperal fever is contagious and that the Philadelphia Practice of Midwifery (1838) omits mention of the disease entirely.

Unthinkable now, but it was commonplace for a doctor or midwife to deliver one baby and then move to the other without washing their hands. Holmes’s words for such a physician? A “death-carrying attendant.”

He also opens with a logical list, a kind of syllogism, something he’d have learned from his humanities education. If all these things are true, then there’s no room left for opposing views.

1. Not all forms of puerperal fever may be equally contagious. But evidence shows the disease appearing again and again among patients of a single practitioner, even when no epidemic is present. That pattern demands explanation.
2. Whether infection travels through the air a physician carries into the sick-chamber or passes directly from his unwashed hands, the practical result is the same. We need not settle the question to act on it.
3. Contagion does not guarantee infection. Even the smallpox vaccine, fresh and carefully administered, sometimes fails. Same for scarlet fever. But no one doubts those diseases are contagious.
4. Seasonal and regional influences may trigger or worsen the disease. But smallpox follows the same patterns of rise and fall, and no one doubts it spreads by contagion. Why should puerperal fever be different?
5. If physicians can be shown to carry death instead of health, no excuse will absolve them. “[W]henever and wherever they can be shown to carry disease and death instead of health and safety, the common instincts of humanity will silence every attempt to explain away their responsibility.”

It made Holmes angry that colleagues could explain the deaths of new mothers as Providence, using God’s will as an excuse for their own failures to stop preventable deaths. 

We do not deny that the God of battles decides the fate of nations; but we […] are particular that our soldiers should not only say their prayers, but also keep their powder dry. We do not deny the agency of Providence in the disaster at Norwalk, but we turn off the engineer and charge the Company five thousand dollars apiece for every life that is sacrificed. Why a grand jury should not bring in a bill against a physician who switches off a score of women one after the other along his private track, when he knows that there is a black gulf at the end of it, down which they are to plunge, while the great highway is clear, is more than I can answer.

I’ll not reprise Holmes’s full review of cases (he painstakingly covers more than half a dozen). You can read the full text that he reprinted in Medical Essays here.

What I want to emphasize is how storytelling was much more than a way to “sell” science for Holmes. He knew that story piqued an emotional understanding of science, which was how doctors could be persuaded to act, and also how public trust could be earned and held.

Here’s his passionate conclusion in full:

It is as a lesson rather than as a reproach that I call up the memory of these irreparable errors and wrongs. No tongue can tell the heart-breaking calamity they have caused; they have closed the eyes just opened upon a new world of love and happiness; they have bowed the strength of manhood into the dust; they have cast the helplessness of infancy into the stranger’s arms, or bequeathed it, with less cruelty, the death of its dying parent. There is no tone deep enough for regret, and no voice loud enough for warning. The woman about to become a mother, or with her new-born infant upon her bosom, should be the object of trembling care and sympathy wherever she bears her tender burden or stretches her aching limbs. The very outcast of the streets has pity upon her sister in degradation when the seal of promised maternity is impressed upon her. The remorseless vengeance of the law, brought down upon its victim by a machinery as sure as destiny, is arrested in its fall at a word which reveals her transient claim for mercy. The solemn prayer of the liturgy singles out her sorrows from the multiplied trials of life, to plead for her in the hour of peril. God forbid that any member of the profession to which she trusts her life, doubly precious at that eventful period, should hazard it negligently, unadvisedly, or selfishly!

I read recently that we respond much more powerfully to troubled characters in fiction than we do to stock types who move from one adrenaline-spiked obstacle to the next. That’s because our deepest emotional responses are driven by three chemicals (dopamine, cortisol, and oxytocin). These brain responses are strongest when we truly care about someone else.

Holmes was trying to do something similar by creating a moral dilemma within the physicians he addressed. The doctor who cared nothing about exposing his patients to risk had no soul. But the doctor who could imagine a family’s grief and wrestle with his own culpability was more complex, more colorful, more worthy of trust.

If you’d been listening to Holmes on that February day, you know which doctor you’d have wanted to be.

Converting the Chief Skeptic

Despite his charms, it took time for Holmes to push his reforms. People thought he looked too young. One woman ordered him out of her house when he accompanied a senior physician during his medical training. “Take him away!” she cried. “This is no place for boys.”

Holmes’s colleagues respected his medical skill, but thought him “impaired” for writing poetry. And not all readers of The Atlantic loved him. To some he was a “tiresome little man.”

As one biographer explains, Holmes “disarmed criticism…by courageously persisting in the same method which had originally produced it, namely, by the most fearless intimacy with his audience, never keeping back any jest or any expression of confidence.” In a word, he was not afraid to make himself vulnerable in his writing. 

Holmes and Hawthorne shared pages in The Atlantic Monthly and also knew each other through the Saturday Club, a gathering of literary celebrities that included Ralph Waldo Emerson, Henry Wadsworth Longfellow, and Harriet Beecher Stowe hosted by the publisher James T. Fields. Hawthorne was quiet and shy, brooding around the edges, but Holmes loved to regale the group. As Annie Fields recalled, “with Dr. Holmes sunshine and gayety came into the room.”

The two writers developed a close intellectual relationship, commenting on each other’s manuscripts and commiserating with one another over the dangers of pseudoscience and careless experimentation. So it was no surprise that when he grew ill in 1864, Holmes was the only doctor that Hawthorne would see. Hawthorne had watched a friend die of pneumonia while a quack prescribed a variety of ineffective drugs, poultices, even cupping and blistering, to no avail.

As the two men walked the Boston streets, Holmes conducted a “talking exam,” listening while Hawthorne reported his symptoms of indigestion and fatigue. Holmes recognized that Hawthorne suffered from a profound sense of despondency which signaled imminent death, that there was no cure but compassion. This was an intimate moment—as vulnerable as the introverted Hawthorne had ever allowed himself to be with anyone—and it illustrates Holmes’s ability to reassure even this great skeptic of his good intentions. 

Hawthorne’s simultaneous fear of alternative medicine and medical science left him nowhere to turn as his own death approached. On the one hand were the mesmerists who sought to control the individual through pseudoscientific means. On the other were the Rappaccinis whose misappropriation of science was equally hostile to the privacy of the soul.

Only Holmes could rescue Hawthorne from those two nightmares. He did it as a man of science, as an indefatigable optimist, as a caring friend, and, yes, as a storyteller who knew that passion is one form of understanding.

Web image of A young Oliver Wendell Holmes from PBS.

Hours later, after she has tried all the methods known to her, Agnes is asleep next to Judith’s pallet. Hamnet, overwrought that he is about to lose the “other side to him,” crawls from his pallet to Judith’s side, beginning to feel poorly also. He arranges himself next to Judith in a way that made it almost impossible for people to tell them apart, hoping as Death came to take her, it would be fooled into taking him instead. “And if either of them is to live, it must be her. He wills it. He grips it…He, Hamnet, decrees it. It shall be.” (p. 169) 

When Agnes awakens, she eventually discerns that “her daughter has been spared…but, in exchange, it seems that Hamnet may be taken.” (p. 208) She reinitiates the treatments she had tried on Judith, but nothing works. Hamnet takes his last breath. Agnes wonders how she could have saved him, how she could have missed Hamnet being at risk before she is able to comprehend: “he is dead, he is dead, he is dead.” (p. 219) 

From this event on, O’Farrell constructs the trajectory of the family’s grief with a particular focus on Agnes. Her grief is amplified by resentment and incredulousness over her husband’s return to London soon after the burial because he feared his work as an actor and playwright would lose irretrievable ground with a prolonged absence. These emotions and grievances reach a crescendo over a period of years before understandings are reached and catharsis experienced. 

The Plague Comes for the Twins 

Easily lost in the gripping story O’Farrell tells and the emotional torrents she evokes is the chapter explaining how the plague reached the twins. She takes the modern-day, biomedical understanding of the complex chain of events involved in the spread of plague and weaves it into how she imagines it could happen amidst everyday life in the countryside outside London during the 1590s.  

A basic biomedical reference O’Farrell could have consulted in piecing together a credible sequence of events leading to the twins’ infections would likely include the same details provided in a summary of plague spread published in the 2021 volume of the American Journal of Medicine*: 

An ancient disease, its bacterial agent (Yersinia pestis) is an aerobic, gram-negative coccobacillus in the family Enterobacteriaceae. Its primary vector for transmission is the Xenopsylla cheopis flea, although roughly 80 species of fleas can carry it. During the Black Death, the flea was transported by the black rat or Rattus. A controversial new theory argues that ectoparasites such as human fleas and lice also spread the disease during the second plague pandemic [1347-1665]. Fleas can also survive in infected clothing or grain. The bacteria multiply in infected rodents and block the fleas’ alimentary canal, causing the fleas to regurgitate the Y. pestis bacteria into its animal host…Plague transmission is generally from infected fleas by rodent vectors or, rarely, in clothing or grain but may also occur through ingesting contaminated animals, physical contact with infected victims, or direct inhalation of infectious respiratory droplets. 

O’Farrell could also find plenty of well-researched historical accounts of the plague impacts at the time and place she set the novel. The plague affecting Stratford then is thought to have first entered England in 1348 from ships docking in cities along the southwestern coastline. England struggled with it almost constantly for more than 300 years until it dissipated after 1665. From this biomedical and historical background, O’Farrell created a realistic framework for the story, and a reasonable representation of the all the factors needed for the infection to find the twins in 1596 Stratford.   

She starts her explanation of how the twins got infected by specifying that,  

two events need to occur in the lives of two separate people, and then these people need to meet. The first is a glassmaker on the island of Murano in the principality of Venice; the second is a cabin boy on a merchant ship sailing for Alexandria on an unseasonably warm morning with an easterly wind. (p. 140) 

The glassmaker is filling an order for decorative glass beads received from a dress shop in Stratford, England. But, because of a recent hand injury, a fellow worker is given the job of packing the order. This worker doesn’t know that the glassmaker “usually pads and packs the beads with wood shavings and sand to prevent breakage. He grabs instead a handful of rags from the glassworks floor and tucks them in and around the beads.” (pp. 140-141).  

Meanwhile, the merchant ship has docked in Alexandria, and the cabin boy has been sent ashore for provisions. He quickly encounters a man with a monkey, and the monkey quickly jumps on the cabin boy, and then all over the boy, passing along three infected fleas. One of them accompanies the boy back onboard ensconced “in the fold of the red cloth tied around the boy’s neck, given to him by his sweetheart at home.” (p. 144) The flea doesn’t stay there long. It jumps into the fur of one of the ship’s cats the boy picks up and nuzzles. Soon after the cat is sickened by its passenger and seeks comfort on the hammock of a midshipman, who upon approaching his hammock for a night’s sleep, finds a dead cat. The flea, now needing a new place to live “makes its way, by springing and leaping, to the fecund and damp armpit of the sleeping, snoring midshipman, there to gorge itself on rich, alcohol-laced sailor blood.” (p. 144) Three days later, the midshipman is dead. 

The ship arrives in Murano to pick up cargo including the glass beads. The cabin boy and the glassmaker come eye to eye as the glass beads are loaded onto the ship. And at that moment, the monkey flea, which had found a way back to the boy after time with some of the ship’s rats and its chef, leaped onto the glassmaker. He and many others in his factory subsequently succumb to “a mysterious and virulent fever.” (p. 149) 

In the hold of the ship now heading to England, the progeny of the monkey flea leap from dying rats to cats lying on top of the boxes filled with the glass beads until the cats die. The fleas eventually “crawl down into these boxes and take up residence in the rags padding the hundreds of tiny, multi-coloured millefiori beads (the same rags put there by the fellow worker of the master glassmaker…)”. (p. 148) The ship arrives in London and the boxes of glass beads are taken to a wharfhouse where they are stored for about a month before picked up for further transport. 

O’Farrell ends her tale of how the plague found the twins through the delivery of the box with infected fleas to their final destination. The box of beads “still wrapped in rags from the floor of the Venetian glassworks” is transported to an inn located near the northern reaches of London. (p. 149) Then, a messenger collects the box and takes them by horseback on a two-day journey to another inn near Stratford. O’Farrell adds how during this ride the mass of infectious plague vectors and organisms intensifies. 

The fleas in the rags crawl out, hungry and depleted by their hostless stay in the wharfhouse. Soon, however, they are recovered, rejuvenated, springing from horse to man and back again, then out on to the various people the rider encounters along the way…By the time the rider reaches Stratford, the fleas have laid eggs: in the seams of his doublet, in the mane of the horse, in the stitching of the saddle, in the filigree and weave of the lace, in the rags surrounding the beads. These eggs are the great-grandchildren of the monkey flea.  

The box with the beads and the fleas is now in the town where the twins live. An innkeeper there has it, and gives a boy a penny to deliver the box to the dress shop that ordered it many months before. The fleas have found Hamnet. 

Judith is at the dress shop helping out when the box is delivered.  

The seamstress holds aloft the box. ‘Look,’ she says to the girl, who is small for her age, and fair as an angel, with a nature to match. 
        The girl clasps her hands together. ‘The beads from Venice? Are they here?’ 
        The seamstress laughs. ‘I believe so.’ 
        ‘Can I look? Can I see? I cannot wait.’ 
The seamstress puts the box in her counter. ‘You may do more than that. You may be the one to open them. You’ll need to cut away all these nasty old rags. Take up the scissors there.’ 
 She hands the girl the box of millefiori beads and Judith takes it, her hands eager and quick, her face lit with a smile. (pp. 150-151) 

The fleas have found Judith. 

When Literary Narrative Serves as Biomedical Text 

O’Farrell’s narrative, fictional model of plague spread embedded in her story imagining what could have caused the death of an eleven-year-old boy in 1596 takes into account both the virulence of the infection and the many and varied ways it can spread. To make that point, she, much as would any epidemiologist, tells of others killed as the fleas made their way from Murano to Stratford, such as workers in the glassmaker’s factory, midshipmen on the boat, and various people encountering land-based messengers carrying the box of beads to those awaiting it. In that way, her model also explains how the mortality estimates of one-tenth to one-third of the populations from frequent plague visitations over three centuries could be generated. 

O’Farrell could have left this part out of the novel without losing much of the core storyline or emotion and drama of it. Indeed, the movie version gives it only a few seconds of attention showing the twins’ father walking by a street puppet show during a scene representing the spread of and death from plague delivered from a ship. By including the chapter, however, O’Farrell compounds the drama and emotion, and reveals the complexities involved in our fates.  

And, as I recall the drudgery of reading and mastering the intricacies of infectious disease spread and pathology such as those of bubonic plague, I wish I had O’Farrell’s novel Hamnet at the time. The experience would have been enjoyable and memorable where the experience with biomedical texts were not in either way. Perhaps this application was not in O’Farrell’s mind for the book, but it could go a long way in ridding us of the plague of turgid, mind-numbing, and indecipherable biomedical prose. Whether or not she knows it, O’Farrell has in this novel brought attention to a plague of another house.  

Hamnet
Maggie O’Farrell
Alfred A Knopf; 2020

*From: Glatter JA, Finkelman P. History of the Plague: An Ancient Pandemic for the Age of COVID-19.  American Journal of Medicine 2021; 134(2): 176–181. 

Image Credits

The path of infection of plague from rats via fleas to man, by A.L. Tarter from the Wellcome Collection. Attribution 4.0 International (CC BY 4.0). 
A rat on board a ship, carrying the plague further afield, by A.L. Tarter from the Wellcome Collection. Attribution 4.0 International (CC BY 4.0) 
The word plague hovers above a victim’s face, by A.L. Tarter from the Wellcome Collection. Attribution 4.0 International (CC BY 4.0) 

Although his story opens with the establishment of the Johns Hopkins Hospital in 1876, Barry immediately takes a detour into the history of medicine dating back to Hippocrates, and traces the history of medical/scientific thought from Ancient Greece to the end of the 19^th century. He then introduces a series of physicians, scientists, and medical researchers who will play their parts in the story of the pandemic (this first section is called “The Warriors”) and outlines their training, research, and interactions.  

It isn’t until page 91 that he takes us to the rural Kansas county in which the story of the pandemic begins. For although it was called the “Spanish Flu,” that was actually an eponym of convenience; in fact, the first cases of pandemic flu seem to have arisen on the American prairie. However, newspaper reporting on the new pandemic was felt by the Allies and Central Powers alike to be contrary to the public interest (the war was still raging), so it was left to neutral Spain, whose king had come down with the disease, to publish the early reports. In this section, “The Swarm”, Barry also briefly reviews the basic (not to worry, very basic) microbiology of viruses and the history of some prior pandemics. He follows this with the section called “The Tinderbox,” in which he traces the events leading up to the entry of the United States into World War I, and the importance of that war and the political and social conditions surrounding it in the history of the pandemic. From here on in the influenza itself takes center stage; in sections called “It Begins,” “Explosion,” “Pestilence,” “The Race,” and “The Tolling of the Bell,” the rapid and lethal course of the pandemic is described in gripping (no pun intended) detail. The last two sections discuss the scientific advances (and some false starts) brought about by the cadre of researchers working day and night to tame the outbreak, and then Barry finally turns to the retreat of the virus and ultimate end of the pandemic. The book ends as it began, returning to the stories of the individual men and women of science who engaged in the battle to beat the disease of which it had initially been said by many that “[t]his was, after all, only influenza.”  

For anyone seeking to understand the 1918 influenza pandemic not only from a scientific and medical historical standpoint, but also with an appreciation of the political and sociocultural milieu in which it took place, you can’t do much better than Barry’s work. It is not short—it clocks in at 461 pages, with another nearly 40 pages of endnotes and a 20 page bibliography—but it is well-paced and reads smoothly; the narrative carries you along, a testament to the author’s writing style. Barry succeeds in putting a human face on the pandemic and creates a mental image of the horror of pandemic disease which can stand up alongside those we have of the Black Death of the mid-fourteenth century, with which it is often compared. For those of us who know the flu as a seasonal visitor, (for most of us a major annoyance, but nonetheless a disease that kills tens of thousands each year), the images of massive and rapid death—villages abandoned except for piles of corpses, trains that “left one station with the living…[and]…arrived with the dead and dying”—seem surreal. Barry paces the book in such a way that one can almost hear the stopwatch ticking in the background; The Great Influenza is scientific and historical reporting done with great attention to detail and to getting the medical facts right, but it is reporting done with a novelist’s flair.  

Even as the pandemic begins to recede, leaving in its wake not only the dead but those living with its sequelae, such as post-encephalitic syndromes (the Woodrow Wilson/Treaty of Versailles anecdote is particularly striking), the helplessness of medical science is reaffirmed; the pandemic recedes of its own accord, because the virus mutates to less virulent forms, and the very large number of those who have survived helps to create herd immunity.   

In the book’s Afterword, added in 2018, the author discusses and compares influenza pandemics which followed the 1918 experience, talks about some of the antiviral drugs introduced over the years and how they work, and speculates about what the next great influenza pandemic might look like and how it might be prepared for. His concern was prescient, although it would be a coronavirus, rather than influenza, that would cause widespread death and societal disruption. In fact, one of the most jarring aspects of this story is the fact that, if one changes the dates and the names, the tale bears an uncanny resemblance to the COVID-19 story, right down to the attempts at minimization by the government and even the isolation and victimization of an ethnic group (in 1918 the Germans, who were the enemy in the world war, rather than Asian-Americans, as it would be during COVID).  

The Great Influenza is a detailed, highly readable, and sobering account of an episode which demonstrated once again that despite what we may think, we are not the masters of the world in which we live, and that a microbe could rapidly kill on a devastating scale and upend society—again—and there was initially little that could be done to stop it.  

THE GREAT INFLUENZA: A Story of the Deadliest Pandemic in History
John Barry 
Penguin Books, New York, 2004 (reissued with new afterword, 2018)
461 pages 

A previous version of this review was published in the NYU Literature, Arts, and Medicine Database.
Web image by Medhum.org

The modern world is full of inexplicable conflicts. As one who has spent my life developing vaccines against infectious diseases it is puzzling to see the growing opposition to vaccination, which in the United States and other developed countries have eliminated or limited diseases that once decimated populations. I am old enough to remember as a child the deaths of other children, and indeed as a child I suffered three serious infectious diseases, one of which caused temporary paralysis of my face. 

Later in life, I graduated medical school and became an intern at a large metropolitan hospital in Cleveland. One of the common infections I saw in children was due to a bacterium called Hemophilus influenzae type B, which causes meningitis and epiglottitis (swelling of the structure at the top of the trachea that leads to the lungs). I treated those infections with antibiotics, but that succeeded best if the illnesses were in early stages. I remember one night on duty when a 3-year-old gasping for air was brought in to the Emergency Room by his father. The child had been put to bed that evening appearing to be healthy, but became ill hours later. I rushed into the room ready to help but in seconds, before I could do anything, the child died before my eyes. I will not forget the anguish of his father, or the anguish of other parents I saw whose children were ill with infections. Owing to the later development and employment of a vaccine against H. influenzae type B, the disease has disappeared from the United States. 

In part, the current opposition to vaccines can be attributed to the absence of these diseases they cause, which makes people feel invincible, and in part to a society in which communication of lies and fabrications is easy and rife. Modern communication allows dissemination of arguments based on fabrications to masquerade as facts, and to allow some to profit from those fabrications. Another example of a foolish approach to the issue of vaccination is the attempt by the current administration to break up the measles-mumps-rubella vaccine into three separate injections, despite years and years of safe use of the MMR vaccine that has dramatically controlled those diseases. The effects on public health will be awful. 

Although there is no easy way to deal with this situation, I have long thought that including education in statistics for all school children would be one useful step, so that they understand the relations between risk and benefit when they become adults. The fact of the matter is there is no choice in life that is without risk. The question is what is the ratio of risk to benefits in making that choice? All statistical analyses show that vaccination has little risk and great benefit, so why should we let lies about vaccination prevail? 

All licensed vaccines go through a process involving 5 Phases: Phase 1 involves testing a vaccine in a small number of people. Phase 2 involves increasing the number to several hundred. Phase 3 involves thousands of vaccinees, compared to a group of placebo recipients, checking for safety and efficacy of the vaccine. Phase 4 is after licensure, when observations are accumulated in millions of vaccinees. Phase 5 involves collection and analysis by CDC and potentially other organizations of reports by physicians about safety and efficacy of the vaccine. 

Obviously, if a reaction to a vaccine is frequent, that will be detected in the first three phases. If a reaction is uncommon but significant, it will be detected in phase 4. (Actually, a vaccine against rotavirus, an important cause of infantile diarrhea, dehydration, and death, was taken off the market because of phase 4 findings, to be replaced by a safer vaccine developed in my lab.) The problem is that when millions are being vaccinated, bad things are certain to happen by chance. The question then is are they caused by the vaccine? The answer to that question can only be ascertained by careful study, not by jumping to conclusions. 

Web image from Wikicommons.

Then one day Dymov develops diphtheria, evidently contracted by “sucking up mucus through a pipette from a boy with diphtheria. And what for?  It was stupid… just from folly.”  Dymov soon becomes seriously ill and then dies. Suddenly, Olga is overcome with guilt and grief. Too late, Olga realizes that her husband was a hero.

Chekhov based this story on the real-life love affair between his good friends Isaak Levitan, a well-known (and married) artist, and Lika Mizinova, a young unmarried teacher, who had for many years been infatuated with Chekhov while he toyed with her affection.  In this interpretation, Chekhov bases the character of Dymov largely on himself, portrayed as a dedicated and disciplined worker who has no time to spare for frivolous romance. However, in reality, Chekhov had playful relationships with many women, but eschewed commitment until late in life. 

Another way of looking at the story is the dramatic tension between practicality (science, public health, and social consciousness), as exemplified by Dymov; and emotion (art, adventure, romance), as exemplified by Ryabovsky.  Olga at first chooses the latter, but Dymov’s death turns the tables.  After he becomes a martyr to science, she suddenly finds him more interesting and mourns her loss.  Was his death the result of a foolish mistake?  Did her infidelity play a role, perhaps by distracting him while he was aspirating the pus?  Or might Dymov have deliberately performed the foolish procedure, realizing that the infection would cause his death?  

The Wife & Other Stories. The Tales of Chekhov. Volume 5, New York, The Ecco Press, 1985.
Translated from the Russian by Constance Garnett.  
Shelby Foote (Ed.) Chekhov’s Later Short Stories. 1888-1903, New York, The Modern Library, 1999.
Translated from the Russian by Constance Garnett.  

A previous version of this review was published in the NYU Literature, Arts, and Medicine Database (Litmed).

Reviews of Chekhov’s Stories

Cold Eye, Warm Heart: Medicine and Anton Chekhov  

Jack CoulehanAug 6, 2025

An Awkward Business by Anton Chekhov 

Jack CoulehanJun 11, 2025

The Grasshopper by Anton Chekhov

Jack CoulehanMay 11, 2025

Ward No. 6 by Anton Chekhov

Jack CoulehanMar 11, 2025

Ionych by Anton Chekhov 

Jack CoulehanMar 11, 2025

A Doctor’s Visit  by Anton Chekhov 

Jack CoulehanMar 11, 2025

A Nervous Breakdown by Anton Chekhov 

Jack CoulehanFeb 11, 2025

Enemies by Anton Chekhov

Jack CoulehanJan 11, 2025

Alive: Our Bodies and the Richness and Brevity of Existence by Gabriel Weston 

Boston: David R. Godine, 2025, 304 pages 
ISBN 9781567928235 

The physician experience, medical history, motherhood, anatomy, and worries about her diseased mitral valve are tenderly sutured together by ENT surgeon Weston in her exploration of “the poetry of the body.” In thirteen chapters, she eloquently contemplates “the strange, unbridgeable gap that exists between the body science describes and the one each of us is living inside right this moment” (p194). In describing the anatomy of bones, brain, breasts, genitals, gut, heart, kidneys, liver, lungs, skin, and womb, Weston writes with a wit and intense curiosity reminiscent of popular science writer Mary Roach. But the book’s splendor arises from its attention to the art of doctoring. Weston notes how good physicians require a kind of “bifocal vision” that allows them to see the generalities of the human body but also the unique details of an individual patient. She extols empathy and elevates vulnerability: “We are not separable from those we care for, just as our strength is not separable from our vulnerability” (p263). Melding science and sentiment, mixing professional life with personal life, Weston enlivens anatomy and pays homage to the physician-patient relationship.  

The Land in Winter by Andrew Miller 

London: Sceptre, 2024, 384 pages 
ISBN 9781529354270 

Andrew Miller’s remarkable 1997 debut novel Ingenious Pain chronicles the complex life of an 18^th century highly skilled English doctor incapable of feeling pain. Twenty-seven years and many novels (Oxygen, Pure, The Optimists) later, Miller’s latest book spotlights a main character who also happens to be an English physician – but this flawed human being hurts (especially emotionally). Eric Parry is a 36-year-old country doctor having an extramarital affair with a married woman while his wife Irene is pregnant. Next door to their cottage is a farm owned by Bill Simmons and his pregnant wife Rita who suffers from mental illness and enjoys reading science fiction. It is winter (December, 1962 – January, 1963) and for a time the rural community is paralyzed by a brutal blizzard. Happy endings are in short supply here. One of the pregnant women has a miscarriage while sitting on the toilet. Characters get injured. Some patients die. Eric’s infidelity is exposed. Still, compassion and empathy occasionally sprout amidst the bleakness and the cold. Irene is cognizant that her husband’s work is hard as he “had to deal with people’s suffering all day” (p55). Eric excels at examining patients with a manner that “calmed” them. Secrets, loneliness, belonging, complicated personal relationships, and poor decision-making are essential elements of the plot. The story asks readers to contemplate whether virtuousness is a necessary requirement to be a “good doctor.” 

Doc or Quack: Science and Anti-Science in Modern Medicine by Sander L. Gilman 

London: Reaktion Books, 2025, 320 pages 
ISBN 9781836390152 

Bloodletting and purging (“heroic medicine”) employed for a wide array of diseases. Laetrile (a chemical present in apricot seeds) used for treating cancer. Hydroxychloroquine and Ivermectin prescribed for COVID-19. Spanning centuries, the list of wacky, ineffective, and sometimes dangerous remedies for illness is quite lengthy. In this standout history of scientific medicine from the mid-19^th century to the present, Gilman navigates “the ever-shifting boundary between good medicine and quackery” (p15). He reviews the rise of allopathic medicine that resulted from “following the science” as discovery and knowledge migrated from the laboratory to the bedside. He writes about the model of the physician-healer, the placebo effect (along with the morality of deception), superstitions (of both doctors and patients), and the faddish nature of medical practice. Gilman is rightly concerned about physicians experiencing burnout and patients feeling disconnected from their doctors in truncated office visits. He wonders if empathy and efficacy can coexist in contemporary healthcare. Three “case studies” are presented: peptic ulcer disease, the development of ophthalmic surgery, and acupuncture for back pain. A thoughtful study of historically “good” and “bad” medicine and the occasional blurring between the two. 

Additional recommended books published in 2025: 

The Mind Electric: A Neurologist on the Strangeness and Wonder of Our Brains
by Pria Anand 

The Age of Diagnosis: How Our Obsession with Medical Labels Is Making Us Sicker
by Suzanne O’Sullivan 

Web photo by Bermix Studio 

A child of unconventional, British-born parents, raised in the bucolic countryside of Vancouver Island, British Columbia, her relentless pursuit of science began in a love of animals, carrying her through two Canadian universities to a University of Chicago PhD in pharmacology and tenuous postdoctoral positions investigating the pituitaries of whales and armadillos. The research sent her to sea with grudging whalers and to inhospitable deserts by night. She married fellow pharmacologist Ellis Kelsey, followed him for his work, and became a mother of two daughters. Lack of paid opportunities for a woman scientist sent her commuting to medical school in Chicago where she obtained an MD degree in 1950 at age 36, while her husband kept the home and family together. She was working as a G.P. locum tenens and as an editor for JAMA. After a stint in South Dakota, the family relocated to Washington in 1960 where she began her lengthy career in the FDA, rising through the ranks to positions of prominence. Not long after the move, her stance on thalidomide earned her the Distinguished Federal Service Award of 1962, presented by President J​ohn​​ ​F. Kennedy. It also brought widespread admiration, mountains of fan mail, several other honours, and the resentment of male colleagues. Ellis died suddenly in 1966, but she kept working into her 90s, taking on the public-health challenges of other notorious “remedies” seeking approval. Kelsey’s fame eventually subsided but rose again in 2015 with late honours and her death at 101 years of age.  

Cheryl Krasnick Warsh​,​ who lives and works on Kelsey’s parental home of Vancouver Island, has given us a wonderful biography. With many previous publications in gender history and the history of alcohol and other drugs, Warsh is well placed to handle this vast and ​multifaceted​​ ​topic, sensitive to the misogyny of Kelsey’s century and with expertise on the nature and fortunes of licit and illicit substances.  

In twenty short chapters, Warsh divides this long life into three ​​segments– before​,​ during, and after thalidomide– and identifies her subject in three different ways. She describes “Frankie’s” early years in simple prose, reminiscent perhaps of Gertrude Stein or Emily Carr. Quirks and disputes in the Oldham home become evidence of a high-functioning, dysfunctional family. As a young woman, “Frances Oldham” delved into science studies at what would become University of Victoria and McG​i​ll in Montreal but made the ​trip ​back home every summer. She slipped into the laboratory of distinguished pharmacologist E.M.K. Geiling at the University of Chicago, when he believed the applicant was male. Despite his initial skepticism, Geiling fostered her career and supervised her doctorate. In 1937, she worked on the lethal side-effects of elixir sulfanilamide and determined that the solvent was responsible. At that time, she also became interested in researching harmful effects of pharmaceuticals on pregnancy and explored the legal protections (or lack thereof) for their consumers. With Geiling and Ellis Kelsey, Frances Oldham wrote a pharmacology textbook, one of the first in America, that went into four editions. These experiences, her medical degree and the work with JAMA were excellent preparations for her concerns about thalidomide. Now she was “Dr Kelsey,” one of two in the same home. 

Kelsey first doubted the value of this new drug when the side effect of peripheral nerve damage seemed to have been excluded from the incomplete applications and their inadequate trials. Further delay allowed for the early reports of fetal damage (coming from newspapers rather than manufacturers) to add to the concerns. While she succeeded in blocking the approval of thalidomide, it had managed to make its way into the US anyway, in the form of free samples given to practitioners sloppily engaged as researchers in shoddy “clinical trials.” Warsh carefully tracks the resultant American harm through reports of at least 56 damaged or dead infants documented in a survey of city health officers in 1962—probably merely the tip of an iceberg. She also probed the tragedy’s impact on attitudes to abortion, respect for the disabled, and increasing caution over medications. 

Beyond the thalidomide story, this biography provides a good sense of the evolving field of pharmacology and interesting chapters on the thorny history of several famous drugs–Krebiozen, laetrile, dimethyl sulfoxide (DMSO), artificial sweeteners, and diethylstilbestrol (DES)–and the harmful impact of Xrays on the pregnant belly. Kelsey found support from other women scientists, in particular Barbara Moulton and Helen Taussig​,​ who became her friends. 

Warsh has tapped into a wealth of sources—extending well beyond the numerous publications, FDA documents, and newspaper reports. She interviewed Kelsey, aged 99, in 2014 and spoke with her colleagues, daughters and other family members. She made excellent use of the personal papers, sorted by the pharmacologist herself with the help of FDA historian John Swann; they contain more than 78,000 items and occupy more than 100 feet of shelving in the Library of Congress. Moreover, Warsh follows the court decisions, changing legislation and rules governing not only drug approvals but ​also ​the ordering of female lives in terms of employment and reproductive freedoms. Yet she handles all this information with a deft light touch, accessible language and playful humour.  

A great read about a great scientist and a fascinating era in biomedical science. 

Frances Oldham Kelsey, the FDA, and the Battle Against Thalidomide
Warsh, Cheryl Krasnick
Oxford University Press. 
New York, 2024-03-15

Photos of Frances Oldham Kelsey from Wikicommons

Cheryl Krasnick Warsh Interviewed at Library of Congress

For more than a decade, I kept running into the Emperor of All Maladies at various bookstores, book shops, and libraries. Siddhartha Mukherjee’s Pulitzer Prize winning biography of cancer would glare at me from its position on the bookshelf, daring me to read it, but each time I saw it, I would mull over the idea of reading a 450 page history of medicine book, shake my head, and move on to something lighter and less strenuous. Mostly, tired from my day job as a family doctor, I just wanted to read something less medical.

Last fall, it happened yet again. I ran into the Emperor of all Maladies once more, this time at my local library’s annual used book sale. For the princely sum of $1, I picked up the book, flipped through it, and thought, why not?

What I discovered was a book that was all that I had expected it to be, and more. Yes, it’s a long, exhaustive read. Yes, it contains long sections of exposition, explaining the details of how protein kinases and mRNA work on a molecular level. But it’s also eye opening and moving and manages to make the connection between what happened in hospitals and clinics a hundred years ago with the state of not just modern oncology, but modern medicine as a whole.

Last fall, I joined MedHum and before long, we realized MedHum needed a podcast. But what would we talk about? And that’s when I realized that Mukherjee’s book, with its vast scope, and comprehensiveness would be the perfect starting point for the show.

Then I thought, I needed to convince someone to read this book with me. And who better than my literary podcast buddy, Mr. Luki Danukarjanto. Luki is a career coach, writer and the founder of Focus Inspired, a service dedicated to helping people achieve meaningful career change. He also lives in Toronto.We’ve been talking about books on the W5H Book Club podcast together for the last several years. Why not read about medical humanities?

The result is two dudes who love to read talking about a great book.

Welcome to the premiere episode of Apollo On Call. Enjoy.

Dr. David Hsu

Transcript from this episode

“At once it struck me what quality went to form a Man of Achievement, especially in Literature, and which Shakespeare possessed so enormously — I mean Negative Capability, that is, when a man is capable of being in uncertainties, mysteries, doubts, without any irritable searching after fact and reason.”¹ 

The young physician then went on to cite Samuel Taylor Coleridge as a poet whom he considered deficient in negative capability because he was “incapable of remaining content with half-knowledge.”¹ What exactly did Keats mean? That Coleridge was too curious or too intellectual to be a great poet? We’ll never know because Keats, who died of tuberculosis less than four years later, never referred to negative capability again, either in his letters or other writings.  

A single mention in a private letter is not much of a pedigree. Nonetheless, Keats’ casual turn of phrase has generated plenty of writings by others in the centuries that followed. Literary critics generally interpret negative capability to mean being open to the world without having preconceived theories, a willingness to suspend judgment, and/or the ability to function imaginatively in the face of incomplete knowledge (e.g. uncertainties, mysteries). In recent decades notable psychoanalysts and philosophers have championed the importance of negative capability in their own fields. In fact, with the enthusiasm of a dilettante who knows little about literary criticism, I’ve gone so far as to argue that negative capability is an important quality for clinicians to develop.²  

Wait a second! There’s something wrong with this picture. Physicians not “searching after fact and reason”? Doctors “remaining content with half-knowledge”? How can negative capability be a positive quality in scientific medicine? It sounds negative for sure, but not very capable.  

What did John Keats have in mind when he invented the term? In 1816 he had successfully passed his examination for a medical license and joined the Worshipful Society of Apothecaries, yet had also become increasingly ambivalent about a career in medicine. By late 1817 he and his brothers had rented a house in Hampstead, where John devoted himself to writing poetry, as well as taking care of Tom, who was dying of tuberculosis. Keats had given up the idea of practicing medicine. Yet could medical training have had any influence on his concept of negative capability?  

Medicine has a long tradition that attributes a special quality to the diagnostic and therapeutic thought processes of good clinicians, an attribute independent of intelligence, medical knowledge, or even logical deduction—with all due respect to Sir Arthur Conan Doyle and his teacher, Dr. Joseph Bell, who served as the model for Sherlock Holmes. When I was a medical student, my teachers referred to this quality as clinical intuition or clinical judgment. Yet the word “intuition” was always suspect because it smacked of mysticism, and “judgment” was co-opted in the 1970s by clinical epidemiologists, like Alvan Feinstein, who characterized it in mathematical terms of probability and utility, which sounded good but didn’t capture the experiential quality of medical thinking.³  

In an episode of “Star Trek,” when Spock questions Captain Kirk about an apparently foolhardy decision that has endangered the entire crew of the USS Enterprise, Kirk replies, “It’s not logical. It doesn’t make sense. It’s my gut feeling!” Kirk, as usual, had chosen the right course of action and by the end of the episode saves the day. However, even if clinical judgment can’t be reduced to an algorithm, surely it must have more going for it than gut feelings. I recently found an interesting, and I think plausible, definition in the nursing literature: “a judgment in which visual and verbal cues are so rapidly and subliminally observed that their contributions to the final decision are virtually forgotten.”⁴ 

Yet visual and verbal cues can’t stand alone. They require something to integrate them, a process, a creative spin. Some years ago Edward de Bono coined the term “lateral thinking” for an indirect approach to problem solving, involving ideas that might not be obtainable by using traditional step-by-step logic. (Parenthetically, I imagine that for de Bono the more traditional approach to problem solving must logically be entitled “medial thinking, i.e. closer to the center, whatever that means.) De Bono’s lateral thinking seems roughly equivalent to today’s favorite metaphor for creativity, “thinking outside the box.” Alternatively, those of us who slavishly adhere to reason are doomed to remain trapped inside the box, like Schrödinger’s cat, neither dead nor alive.  

Whatever you call it, I find something attractive about attributing a special openness and curiosity to the art of medicine, an openness that permits a greater variety of information to enter the box, rather than kicking the logical brain out of it. In his famous turn of phrase, Keats obviously chose to give “negative” a beneficial meaning. Negative in this context implies passivity, receptivity, and humility , yet it seems these qualities are precisely what made the difference between a competent poet like Coleridge and a truly creative one. Does this sense of negativity have a place in the art of medicine? Does it tell us anything about the difference between merely competent and master clinicians?  

One aspect of the comparison fails immediately. Unlike Keats, whose primary goal was beauty, physicians are heavily invested in truth. So “searching after fact and reason” is the name of the game in medicine, not the road to mediocrity. But other aspects of negative capability seem more promising. What if you view negative capability as intellectual and emotional openness, a willingness to be reflective and mindful about one’s practice? While “reaching after fact and reason” may be a defining feature of scientific medicine, clinicians confront a human reality that remains opaque, even after machines and lab tests have yielded their results. If we as clinicians predicate our care entirely on “irritable reaching,” or abandon patients because of “uncertainties, mysteries, doubts,” we lose much of our effectiveness as healers.  

Of course, poetry is only one of many tools that can assist us in developing the habit of reflectiveness, but for me it offers a glimpse into the paradox of the art of medicine: the ability to function at the interface between detachment and engagement, steadiness and tenderness, resilience and vulnerability, science and art. In pursuing the steadiness and detachment required to master clinical practice, it is tempting to neglect the more difficult project of nourishing engagement and tenderness in our relationships with patients—and with ourselves. In an address to medical students at McGill University, William Osler claimed,  

“Nothing will sustain you more potently in your humdrum routine… than the power to recognize the true poetry of life—the poetry of the commonplace, of the ordinary man, of the plain, toil-worn woman, with their loves and their joys, their sorrows and their griefs.”⁵  

That “power to recognize the true poetry of life” is a function of negative capability. Notice that Osler speaks of sustaining the physician through the “humdrum routine” of professional life, not specifically of patient benefit. Could it be that physicians who develop negative capability are happier, more productive, less likely to burn-out? 

I’ll end with an example close to home. In my narrative medicine elective at Stony Brook, I used to ask students to keep a clinical journal. In one of her final entries, one fourth year student, reflecting on her experience in medical school, wrote, “The practice of medicine is simply poetry in motion. The art of medicine is the validation of everything that makes the human experience. I learned more about myself than I ever imagined….”  

Simply poetry in motion.  

I wonder what John Keats, who rejected medicine for poetry, would have to say about that?  

References

1. Keats J. The Complete Poetical Works and Letters of John Keats, Cambridge Edition. Houghton, Mifflin and Company, 1899, p. 277. 
2. Coulehan J, Clary P. Healing the healer: Poetry in Palliative Care, J Palliative Medicine, 2005; 8: 382-389. 
3. Feinstein A. Clinical Judgment. Baltimore, Williams & Wilkins, 1967. 
4. Cioffi J. Heuristics, servants to intuition, in clinical decision-making. J Adv Nurs 1997; 26: 203-8. 
5. Osler W. The student life. In Osler’s ‘A Way of Life’ & Other Addresses With Commentary & Annotations, eds. S Hinohara and H Niki, Durham, Duke University Press, 2001, pp. 305-330.  
   

Web image from Keats Letter Project.