At the height of the HIV/AIDS epidemic, on Nov. 30, 1993, Larry Kramer, the late writer and gay rights activist, sparred with Anthony Fauci, then director of the National Institute of Allergy and Infectious Diseases, on a C-SPAN call-in program over the Clinton administration’s response to the crisis. Journalist Steve Scully moderated the conversation, also taking calls from civilians whose questions and comments revealed varying levels of understanding of the disease and compassion for those living with it and their loved ones. 

Daniel Fish’s Kramer/Fauci offers a verbatim staging of this conversation, starring Thomas Jay Ryan as Kramer, Will Brill as Fauci, Greig Sargeant as Scully, and Jennifer Seastone as the various callers. All four listen to the C-SPAN recording through in-ear speakers. 

Kramer casts Fauci as the face of an indifferent bureaucracy committing a genocide by inaction. “Tony, if you start that business about, ‘Science isn’t done that way,’” he says, “I’m going to come down there and slap your face.” 

“All right, Larry, hang on for a sec,” replies the career public servant. “I love you, Larry.” 

They are equal parts allies and antagonists, their genuine affection bubbling through their disagreements and making their complicated relationship [1] especially compelling to watch. What I found less compelling was the machine that releases a tidal wave of bubbles, enveloping Kramer. At one point, Fauci lies near the foam in a Titanic-style “draw me like one of your French girls” pose. If the suds are meant to represent lives lost to AIDS, this image risks reducing an enormous human toll to a theatrical flourish; the absurdism does little to illuminate the government’s inadequate response. Seastone dons roller skates at one point and an inflatable chicken suit at another. Are these props meant to suggest that the titular characters are skating past each other? Playing some game of chicken? 

I am still glad I saw the hour-long production. It offers a different experience from watching Fauci sit in a studio or Kramer appear via video screen. The actors roam in the cavernous venue, putting the audience physically inside the conversation. But there is more to theater than the theater itself or theatricality for its own sake—than paltry props and a bevy of bubbles. 

Kramer indicates that, despite Fauci’s diplomatic, controlled persona, he is privately frustrated by the political and bureaucratic constraints holding back AIDS research. What if we had seen imaginings of Fauci’s anger behind closed doors? What if we had witnessed how the men’s relationship evolved—how Fauci began working with AIDS Coalition to Unleash Power, co-founded by Kramer, to expand access to life-saving experimental treatments, or how Kramer later shouted at a government hearing, “Tony, I have called you a murderer in the past, but you are now my hero”? 

What if the production had used its visual language to evoke the toll of the epidemic rather than providing sporadic spectacle? Panels from the AIDS Memorial Quilt. Stories of the 700,000 Americans who died. The more than 1 million Americans living with HIV today, with Black and Hispanic/Latino Americans and men who have sex with men among those disproportionately affected. 

Otherwise, Fish risks reducing AIDS to a metaphor for COVID-19 and its fallout. Kramer/Fauci should not be relevant only because COVID-19 has reshaped the public’s relationship with science, or because Fauci, three decades later, has once again been called on to defend his work during a plague. It should be relevant because the history it depicts remains unfinished. 

C-SPAN recording of the Kramer/Fauci call-in show  

Fauci remembers Kramer 

[1] Fauci, Anthony. “Anthony Fauci on Larry Kramer and Loving Difficult People.” The New York Times, 4 July 2023, https://www.nytimes.com/2023/07/04/opinion/anthony-fauci-larry-kramer.html.  

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Frustrated in their attempts to access information, seek compensation, and prevent future deaths, the families convinced the flamboyant lawyer, Jan Schlichtmann, to take on what was thought to be a hopeless cause. Suddenly, the case seemed to promise a multi-million-dollar settlement. Large industrial concerns, as well as government officials, began to pay close attention. Obsessed with the enormity of the apparent crime, the creative Schlichtmann amassed a huge amount of damning evidence through careful and expensive scientific research. But the accused companies also invested large sums in experienced lawyers and scientists who used other data and legal technicalities to refute the charges. The families lost their case in 1986, and Schlichtmann was financially and emotionally ruined. By that time, 21 cases of leukemia had been identified – 4 times the anticipated rate for the population. A public health report found “no significant differences” in exposure between the leukemia cases and controls, yet concluded that “it is not possible to rule out exposure to this water as a factor” (Cutler et al 1986). 

Author Jonathan Harr began work on A Civil Action in 1986 before the opening of the trial, and he accompanied Schlichtmann to almost all meetings, relied on court transcripts, and conducted many painstaking interviews with the families and opposing lawyers. The result is an omniscient yet intimate perspective on these true events that reads like an action-packed thriller, complete with dialogue. It won many awards and was on the New York Times bestseller list for 65 weeks. It stands as an interesting commentary on the nature of environmental health and on the American justice system. 

Three years later, Steve Zaillian wrote and directed the award-winning film, A Civil Action (1998), based on Harr’s book and starring John Travolta and Robert Duvall. Shlichtmann received $250,000 for the portrayal rights, but is quoted as saying, “John Travolta made more money playing me than I ever did playing me” (Kix 2009). Forty years later, now at age 75, he continues to champion environmental causes, aiming for settlements rather than court cases and recounting his “lessons learned” on the speakers’ circuit. 

Woburn and A Civil Action had coincided with other prominent environmental disasters, caused by industrial failures: Three Mile Island (1979), Love Canal (1977-1979), Times Beach, Missouri (1983), Bhopal (1984), to name only a few. The book and the film contributed to rising awareness about the health risks of environmental damage, and they added to increasing skepticism over the intentions of private entrepreneurs and the courts. They also heralded a period that saw a growing body of legislation aimed to define responsibilities and regulate industrial pollution – measures coming, alas all too frequently, after new problems arose and covering jurisdictions defined only by political boundaries, which have nothing to do with the flow of water and air. In 2022, the United Nations declared that a healthy environment is a human right. Dozens of countries, including Canada (2023) and several American states, have enshrined that ideal in law, even if practicalities and protections lag far behind. 

Less known is that fact that Woburn triggered a public-health preoccupation with “clusters” and the nature of proof (Alexander et al., 1999; Kingsley et al., 2007) Do clusters indicate important dangers or are they unfortunate but random occurrences? A decade later, the Center for Environmental Health Sciences at Massachusetts Institute of Technology reported on its vain “search for causes” in the industrial toxins of the Woburn leukemia cluster (Durant et al., 1995). In 2002, a controlled study, based on Woburn, failed to establish a causal correlation between disease and contamination; it pointed out that incidence had returned to anticipated levels, while 8 consecutive years had seen no leukemia cases at all (Costas et al., 2002). Woburn has also been cited in efforts to provide better statistical evaluation of “clusters” (Waller, 2000). Woburn prompted recommendations to incorporate qualitative methods into public heath reporting (Brown, 2003) and to recognize the value of citizen science and epistemic differences in lay and professional “ways of knowing” (Brown, 1992; Petteway et al, 2019). Woburn is still being cited in public health assessments of environmental causes of malignancy, often with ambiguous outcomes (Binczewski et al., 2026). 

A Civil Action helped prepare the terrain for these many studies with their controls, statistics, and tracking of chemicals–mind you, only those chemicals that are already recognized and detectable. We no longer question the harm in smog and smoking, while improvements in respiratory diseases proclaim the benefits of keeping air clean. It is dismaying that the idea of water pollution as a harm to human health continues to be such a hard sell, while disasters like Flint, Michigan, or Grassy Narrows, Ontario, roil on. 

Water degradation is bad for flora, for fauna, and for the planet. Therefore, it is bad for us too. But for industry, the courts, and even some epidemiologists in their many ways of knowing, it remains an unproven hunch. 

References 

• Alexander, Freda E. 1999. Clusters and clustering of childhood cancer: A review 
• European Journal of Epidemiology 15: 847-852.
• Binczewski, N.R., Morimoto, L.M., Wiemels, J.L., Richardson, D.B., Bartell. S.M., Metayer, C., Vieira, V.M. 2026. Spatial analysis of residential location at birth, PFAS in public water, and childhood cancers in Southern California (2000-2019). Journal of Exposure Science & Environmental Epidemiology 2026 Mar 5:10.1038/s41370-026-00850-1. doi: 10.1038/s41370-026-00850-1. Epub ahead of print. PMID: 41781477; PMCID: PMC13032745. 
• Brown, Phil. 1992. Popular epidemiology and toxic waste contamination: lay and professional ways of knowing. Journal of Health & Social Behavior 33(3):267-81. 
• Brown, Phil. 2003. Qualitative methods in environmental health research. Environmental Health Perspectives 111(14):1789-98.  
• Costas, K., Knorr, R.S., Condon, S.K. 2002. A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water. Science of the Total Environment 300(1-3):23-35. 
• Cutler, J.J., Parker, G.S., Rosen, S., Prenney, B., Healey, R., Caldwell, G.G. 1986. Childhood leukemia in Woburn, Massachusetts. Public Health Reports 101(2):201-5. 
• Durant, J.L., Chen, J., Hemond, H.F., Thilly, W.G. 1995. Elevated incidence of childhood leukemia in Woburn, Massachusetts: NIEHS Superfund Basic Research Program searches for causes. Environmental Health Perspectives 103 Suppl 6:93-8. 
• Kingsley, B.S., Schmeichel, K.L., Rubin, C.H. 2007. An update on cancer cluster activities at the Centers for Disease Control and Prevention. Environmental Health Perspectives 115(1):165-71.  
• Kix, Paul. 2009. In the shadow of Woburn, Boston Magazine, City Life, 22 September:  https://www.bostonmagazine.com/news/2009/09/22/in-the-shadow-of-woburn
• Lagakos, S. W., Wessen, B. J., Zelen, M. 1986. An analysis of contaminated well water and health effects in Woburn, Massachusetts. Journal of the American Statistical Association 81(395):583–596.  
• Petteway, R, Mujahid, M., Allen, A., Morello-Frosch, R. 2019. Towards a people’s social epidemiology: Envisioning a more inclusive and equitable future for social epi research and practice in the 21st century. International Journal of Environmental Research and Public Health 16(20):3983. 
• Waller, L.A. 2000. A civil action and statistical assessments of the spatial pattern of disease: do we have a cluster? Regulatory Toxicology & Pharmacology 32(2):174-83. 
• Jonathan Harr discusses A Civil Action on C-Span 

Web image by Medhum.org

When the Food and Drug Administration (FDA) was created in 1930, its mission was to ensure the safety of prescription medications. In 1962, with the passage of the Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act, the FDA also became responsible for certifying drug effectiveness. Positive results in one or more randomized double-blind clinical trials became the gold standard for approval. Thus, patients were assured that when their doctor prescribed a “hot” new drug that had appeared on the market, it had met the FDA’s rigorous safety and effectiveness criteria.  

Yet, sixty-three years later, near the beginning of Rethinking Medications (2025), Dr. Jerry Avorn writes:  

“In 2021, the Food and Drug Administration (FDA) gave its approval to Aduhelm, a new drug for Alzheimer’s disease that didn’t work, could cause brain damage, and was poised to cost the nation each year a sum the size of NASA’s annual budget. How did the world’s once best prescription drug regulatory body fall so low” (p. 31) 

The FDA not only approved Aduhelm but did so over an almost unanimous negative vote of its scientific advisory panel. What had happened to the promise of safety and effectiveness? Jerry Avorn MD, founder and director of Harvard’s Division of Pharmacoepidemiology and Pharmacoeconomics, argues that the Aduhelm approval resulted from a longstanding decline in the FDA’s regulatory standards, a slippery slope greased by social, political, and especially pharmaceutical industry pressures. Rethinking Medications is a comprehensive assessment of the pharmaceutical industry, the FDA, and their complex relationship in the 21^st century. Much of the book addresses three core issues: Does a new drug work? Is it safe? And what should it cost? Other chapters deal with education, patient empowerment, and the specific examples of psychedelics and pain killers. 

According to Avorn, the FDA’s rigor began to break down during the late 1980s when the agency initiated an accelerated or “fast track” review process in response to the AIDS epidemic, a reasonable change in light of the rapid spread of this incurable and deadly disease. (pp. 30-32) Initially, “fast track” approval involved greater FDA monitoring and quicker action but still required evidence of clinical effectiveness. In the case of AIDS, a hematological marker, CD4 T-cell count, was highly correlated with clinical outcome, which made it an excellent index of effectiveness. 

However, not long afterward, the FDA opened its accelerated approval pathway to medications for chronic, progressive diseases and to use a favorable change in such surrogate markers (e.g. blood tests or images) as substitutes for clinical improvement. For example, in the case of Alzheimer’s disease, reduction in the number of amyloid plaques was considered a sufficient reason to approve Aduhelm, though the study had not documented symptom reduction or slower decline in functioning. While some surrogate markers are good predictors of outcome (e.g. Hb A1c in diabetes), most markers used for chronic disease drug approvals lack strong predictive evidence.¹ 

However, the accelerated track includes a presumed fail-safe mechanism. The pharmaceutical company is required to complete a long-term confirmatory study to confirm clinical effectiveness. By 2022, more than half of new drug applications were being processed in the expedited track, and over 80% of these were approved. (p. 77) The confirmatory study requirement, even if honored by the companies, allowed medications to be prescribed for years before a negative finding might cause approval to be revoked. According to Avorn, the increasing use of surrogate markers as endpoints tells the industry, “You can market your drug if it makes a lab test look better in a short study, compared to a placebo. We won’t be on your case too much about those confirmatory follow-up studies.” (p. 37) [Avorn engages in hyperbole here. Aduhelm was shown to be ineffective and withdrawn from the market in 2024.]² 

Avorn next addresses the safety of newly approved drugs. Serious side effects must be recognized, if possible prior to approval. However, according to the author, the profit motive sometimes outweighs evidence of significant harm. He discusses the case of Vioxx (Merck Pharmaceuticals, 1998), a COX-2 inhibitor approved because it had fewer GI bleeding side effects than other NSAIDs. Several studies subsequently showed that patients taking Vioxx had almost double the number of myocardial infarcts and strokes of those taking other NSAIDs. Nonetheless, Merck rigorously disputed this evidence for several years before finally removing Vioxx from the market in 2004. Largely as a result of the Vioxx scandal, Congress passed the FDA Amendments Act in 2007, which introduced several safeguards for ensuring drug safety. These included (a) creating a nationwide system for monitoring adverse effects, (b) preventing companies from hiding clinical trial results by requiring that all trials be registered in a federal registry, and (c) insisting that companies complete follow-up studies after the drug has been approved. (pp. 167-170) 

In 2007, a far more widespread safety failure was still a decade from being revealed. When Oxycontin was approved in 1995, the FDA believed the long-acting form of oxycodone would result in less abuse potential, since the drug would be absorbed slowly without an immediate “rush” to promote abuse. This belief had a theoretical basis, but there were empirical findings that strongly suggested otherwise. Over twenty years later, a presidential commission (2017) “concluded that the FDA’s mishandling of the evaluation, approval, and use (of oxycontin) was an important cause of the nation’s opioid crisis” (p. 393). 

Anyone who watches broadcast television today will find it difficult to believe that prior to 1997, essentially no prescription drug advertising appeared on television. In 1997, the Food and Drug Administration approved a new rule allowing pharmaceutical companies to state only “major risks” in their ads, rather than its previous requirement of a full list of all possible risks, contraindications, and side effects, which had effectively precluded direct-to-consumer advertising. The industry quickly learned how to package major risks into brief statements aired sotto voce at the end of their commercials under images of smiling patients picnicking in a park. Since then, ads for expensive new pharmaceuticals have spread like wildfire.  

Aggressively promoted new drugs are mostly treatments for chronic, malignant, or degenerative diseases that require continued use over many months or years. The producers, in essence, have monopolies on these products because they are protected by patents from competition for a certain number of years. Without competition, companies are able to charge very high prices, which they justify as necessary to compensate for costs of research and development.  

Avorn identifies several reasons to doubt that excessive R & D costs are a determining factor in pricing new drugs. First, many Big Pharma companies spend more on marketing, most of which is direct-to-consumer advertising on TV and other media, than they do on research and development. Thus, much of the actual “investment” is spent in devising ways to convince consumers that new is better.  

Secondly, most newly approved medications are not innovative, but rather modifications of existing drugs for which the patents will soon expire. The manufacturer seeks to have a replacement drug with a claimable advantage (e.g. fewer side effects, fewer daily doses) sufficiently different to be patented and approved before it loses patent protection on a profitable product. When generic versions of the product appear on the market costing up to 60% less than the original, the manufacturer attempts to maintain profits and market share by heavily promoting its “new, improved version.”  

Third, “breakthrough” medications that employ a newly discovered mechanism, or work dramatically better than available alternatives, are generally the result of NIH-funded basic science and clinical trials performed by university faculty. While the Bayh-Dole Act (1980) allows universities to patent promising new drugs, only pharmaceutical companies have the ability to develop and market the drug commercially. When a company purchases the patent from its home university, the scientists and the university profit from the purchase, but lose control over the medication that results. Although Big Pharma does invest significantly in developing these drugs and bringing them to market, the basic research and initial clinical trials are supported by federal grants. “The largest engine driving the nation’s prodigious ability to bring new drugs to market is the hundreds of billions of taxpayer generated dollars in the National Institutes of Health and other public and philanthropic of biomedical discovery.” (p.197) Not Big Pharma.  

Finally, retail prices for the same drugs in Canada, Europe, Australia, and Japan average about 60% lower than in the United States, even though their manufacturers presumably still make a profit. The real reason they set prices much higher in the United States is simply because they can. Most other countries have mechanisms to control drug prices based on realistic cost/benefit estimates.  

Rethinking Medications is a compelling analysis of today’s pharmaceutical industry and its regulation by the FDA. Big Pharma is clearly the “heavy” in Avorn’s analysis. The FDA failures result from some combination of responsiveness to the need for new therapies in chronic diseases, inadequate resources and personnel to enforce the requirement for confirmatory studies, and the withholding of critical data by pharmaceutical companies. The FDA Amendments of 2007 corrected many of these problems, although the FDA’s fate under the Trump administration is yet to be seen. The prospects are not promising because the Department of Health and Human Services is directed by a man who aggressively promoted hydroxychloroquine as a treatment for Covid and doubts the effectiveness of vaccines.  

Despite Dr. Avorn’s focus on failures and deficiencies, the reader should keep in mind that the American pharmaceutical industry does have a remarkable track record of producing innovative and effective medications. This, of course, does not justify the industry’s rampant profiteering and deceptive practices. It would require strong federal regulation, especially regarding pricing, to address these problems. Here again, the current administration’s anti-regulatory stance makes progress in the near future improbable.  

Notes 
1, Wallach JD, Yoon S, Doernberg H et al. Associations Between Surrogate Markers and Clinical Outcomes for Nononcologic Chronic Disease Treatments. JAMA, 2024; 331 1646-1654. 
2, Two anti-amyloid monoclonal antibody medications, Legembi and Kisunla, have now been approved for treatment of early Alzheimer’s disease. Both have been shown to slow its progression by several months.  

RETHINKING MEDICATIONS
Jerry Avorn MD 
Simon & Schuster, 2025: 512 pages 

Web image by Jaretuz 

Rumor is a major source of vaccine rejection. The author discusses in detail the case of Andrew Wakefield and his contention that MMR (measles, mumps, rubella) vaccine causes autism. This belief, based on a 1998 paper in The Lancet (later retracted) has been shown to be false by numerous large-scale studies, but is accepted by perhaps millions of people throughout the world.    

In Stuck, Dr. Larson makes a strong case that vaccine hesitancy and rejection are widespread and growing global problems. The book is much weaker in proposing effective solutions. It’s clear that simple solutions, based on the premise that resistance will fade away as soon as public health agencies “educate” people, have failed.  Dr. Larson recommends listening more carefully to antivaxxers’ concerns and developing creative pro-vaccine messaging. Since the publication of her book, the massive initiative to vaccinate the American population against Covid has confirmed the extent and multiplicity of antivaccine beliefs in our society. It has also led public health agencies to develop more sensitive and engaging messaging than in the past. Nonetheless, the core problem remains.  

Stuck
Heidi J. Larson 
Oxford University Press, New York, 2020:  155 pages. 
A previous version of this review was published in the NYU Literature, Arts, and Medicine Database.
Web image by Medhum.org

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.

The artist depicts Chekhov as he was in the early 1890’s, soon after he had purchased a small, dilapidated estate and moved there from Moscow with his family. In addition to serving as country doctor and public health official in Melikhovo, Chekhov at that time was composing many of the stories and plays that made him one of Russia’s most well-loved writers and a major influence on 20^th century literature. How was he able to pursue two such different and demanding careers? Several years earlier, at the height of Chekhov’s early literary success, his friend Alexi Suvorin had urged the young writer to give up medicine. Don’t spread yourself too thin, he said. You’ll never reach your potential unless you concentrate on writing. In response, Chekhov wrote, “You advise me not to chase after two hares at once and to forget about practicing medicine. Well, I don’t see what’s so impossible about chasing two hares at once… Medicine is my lawful wedded wife and literature my mistress. When one gets on my nerves, I spend the night with the other. This may be somewhat disorganized, but then again, it’s not boring, and anyway, neither loses anything by my duplicity.” (1) In this famous passage, the 28-year-old writer dances lightly over a fundamental truth of his life and identity. In fact, Chekhov’s career was not so much a matter of jumping from one bedroom to another, as was the case perhaps with the poets Wallace Stevens and T. S. Eliot, or the composer Charles Ives. Rather, Chekhov thrived on the effective, if not always seamless, integration of the arts of medicine and writing, which reinforced one another throughout his creative life. This essay explores that integration, and the manner in which Chekhov’s cold eye (objectivity) and warm heart (compassion) reveal themselves in his medical and literary lives. 

DOCTOR CHEKHOV  

“Medicine Is My Lawful Wife” 

When he graduated from the Moscow State University School of Medicine in June 1884, Chekhov was already earning his living as a professional writer. The grandson of serfs, Anton was the third of six children in a poor merchant family from Taganrog, a southern provincial town on the shore of Sea of Azov. His father had moved the family to Moscow after going bankrupt in 1877. By the time Anton entered medical school on a scholarship in 1879, the Chekhovs were living in squalor. His father had a dead-end job. His older brothers were alcoholics and generally unemployed. Anton soon discovered that he could ameliorate the situation by selling comic sketches to local magazines for eight kopecks per line. This was a type of moonlighting he loved. He wrote obsessively, often knocking off a story or two each night, after spending the day listening to lectures or working in the hospital. Chekhov ultimately published more than 200 pieces while a medical student, most of them under his preferred pseudonym, Antosha Chekhonte. 

Chekhov was a natural storyteller. Thus, it wasn’t surprising that the newly minted Doctor Chekhov continued to write, even after he opened his office and patients began to arrive. “Continued to write” is an understatement. Chekhov published 54 stories in 1885, 76 in 1886, and 57 in 1887. His work evolved from humorous sketches to longer, more serious stories for leading literary journals. In 1888 Chekhov won the prestigious Pushkin Prize and published “The Steppe,” his longest and most innovative story to date. Ivanov, his first full-length play, had a successful premiere in St. Petersburg in January 1889. By that time the young doctor had become one of the best known writers in Russia. 

Yet Chekhov always saw himself as a physician, even though in 1889 he did, in fact, retire from a normal paying practice; after that, he offered his medical services at no charge, even though the generous Chekhov often found himself financially strapped. He took care of the peasants near Melikhovo (as depicted in the painting), donated his services to the government as a district physician, and engaged regularly in public health initiatives. In less than five months in 1891, Chekhov reported seeing 453 patients at a district health center and making 576 house calls, in addition to his home practice. (2) Throughout his life, Chekhov also was heavily involved in grass roots activism, building schools for peasants, raising funds to help famine victims, and, later, near the end of his life, supporting the establishment of a sanitarium for tuberculosis victims at Yalta.  

“My Debt To Medicine” 

One of the best known of these public health efforts was his 1890 epidemiological survey of health and social conditions in the prison colonies on Sakhalin Island. Traveling by himself, Chekhov journeyed six weeks by train, steamboat, and horse-drawn carriage across Siberia to reach the 1000-km long Pacific island on which the Czarist government had recently established a notorious gulag. There, he embarked on a one-man, three-month survey of the population, tenaciously picking his way from settlement to settlement and from house to house, often by foot.  

Biographers have long tried to pinpoint his motivation for this perilous journey. During the year prior to the trip, Chekhov had undergone a crisis of confidence. In a letter to Suvorin, he opined, “I don’t love money enough for medicine, and I lack the necessary passion—and therefore talent—for literature. The fire in me burns with an even, lethargic flame; it never flares up or roars… I have very little passion. Add to that the following psychopathic trait: for two years now, seeing my works in print has for some reason given me no pleasure.” (3) He reported symptoms suggestive of clinical depression, perhaps precipitated by grief over the death of his brother Nicholas from tuberculosis. There was also a literary issue. The master of the short story had promised himself that he would create a Tolstoy-like novel that would confirm his status as a serious writer. But he was unable to do so.  

Undoubtedly a major factor for choosing Sakhalin was Chekhov’s desire to pay his debt to medicine. He had recently developed a scientific interest in penology and had read about the dismal conditions in the Siberian gulag. He saw an opportunity to influence this situation by obtaining accurate data on the health status of Sakhalin convicts. He had never completed the research thesis (the equivalent of a Ph.D.) that would make him eligible to be a medical specialist or professor. Hence, his notion of “my debt to medicine”—he would perform a survey, write his thesis, and become a teacher. 

Ultimately, Chekhov claimed to visit every settlement and survey every household on Sakhalin Island, using a 12-item data collection form. He said he completed over 10,000 of these forms in three months, a feat that (if true) qualifies Chekhov as the speediest shoe-leather epidemiologist of all time. After his return to European Russia, the author found it difficult to organize his data into a coherent study. While he had planned to write a strictly scientific monograph, his creative spirit struggled with the limitations of science. What about his personal experience? What about the interesting stories? After struggling for years, in 1895 Chekhov published The Island of Sakhalin, a curious (but engrossing) mixture of journal, geography, history, medicine, statistics, and travelogue. (4) Unfortunately, the faculty of the University of Moscow was unimpressed.  

“As I Grow Older, the Pulse of Life in Me Beats Faster” 

Picture the mature Chekhov—a middle-aged bachelor, longish face, rather neatly trimmed beard, a prince-nez clipped to the bridge of his nose. His household included his aging parents and his sister Masha, an unmarried schoolteacher who had become his confidant and secretary. His three surviving brothers looked to him for guidance and financial help. Anton was popular, witty, and generous. Among the guests at Melikhovo, there were frequently female admirers. Chekhov’s encounters with women were flirtatious and obviously enjoyable. He had teasing, sexually charged relationships with several women, but whether any of these liaisons are actually “affairs” is uncertain.  

The doctor in the painting already suffered from the tuberculosis from which he would die at the age of 44 years. In fact, he first coughed blood as a medical student. Yet, Chekhov dismissed that episode and each subsequent episode that occurred with disheartening regularity as “influenza” or “bronchitis,” steadfastly refusing to label himself consumptive. As a physician Chekhov must surely have understood the meaning of his symptoms. Was his denial simply a face to show others? Or was his denial so great that it made him unaware? The cat finally came out of the bag in early 1897. While dining at a restaurant in Moscow, Chekhov had a violent spell of hemoptysis that left him critically ill. For the first time, he sought medical treatment and entered the clinic run by Dr. Ostropov, one of his medical school professors. Chekhov’s chronic illness progressively worsened. At the insistence of his doctors, Chekhov left his beloved Melikhovo after 1898 and lived mostly at a new home in the sunny Black Sea resort of Yalta. 

It was also during these last years that the bachelor writer courted and married Olga Knipper, an actress with the Moscow Theater Arts Company. Even after their marriage in 1901, Olga remained at work in Moscow during much of the year, while the invalid Chekhov lived in Yalta, theirs being perhaps one of the earliest examples of the modern two-career commuter marriage. Chekhov found himself able to devote less and less of his waning energy to writing, especially since he refused to give up his social and philanthropic activities. Nonetheless, between 1898 and his death in 1904 Chekhov completed some of his greatest work, including several stories, two novellas (“Peasants” and “In the Ravine”), and his last plays, The Three Sisters (1900) and The Cherry Orchard (1903).  

COLD EYE, WARM HEART 

Chekhov’s Doctors 

Several characteristics of Chekhov’s work reveal the influence of medical training and practice. He used clinical knowledge to lend accuracy to his descriptions of disease and medical situations. This characteristic is perhaps most clearly seen in the characterization of mental disorders. For example, the title character in Ivanov is a subtle portrait of a man suffering from clinical depression, who eventually commits suicide. The young heiress in “A Doctor’s Visit” presents symptoms we would now label as generalized anxiety or panic disorder. The title character in Uncle Vanya appears to have a neurotic depression, a condition that meets today’s DSM 5 criteria for Persistent Depressive Disorder. In the peculiar story called “The Black Monk,” Chekhov describes a psychotic condition, presumably schizophrenia.  

Chekhov also drew from his medical experience in creating a multitude of physician characters. Doctors play significant roles in nearly 30 stories and in all of his major plays, except The Cherry Orchard. The author’s sensibility as a medical insider gives insight and poignancy to these characters, who range from committed altruists to lazy bureaucrats to burned out cases. Chekhov knew too much about the contemporary state of medical science to portray his doctors as curing many people. Thus, they often appear impotent. Yet, at their best Chekhov’s doctors convey the seamless fabric of tenderness (compassion) and steadiness (detachment) that lies at the heart of good medical practice. They also demonstrate courage, altruism, and self-effacement. For example, in “The Grasshopper” (1892) Dr. Dymov dies as a result of contracting diphtheria from a patient. Dr. Kirilov in “Enemies” (1887) demonstrates extraordinary devotion to duty by leaving his distraught wife and dead son in order to make an emergency house call.  

Perhaps Chekhov’s most textured portrait of a good physician appears in “A Doctor’s Visit” (1898). The protagonist, Korolyov, is a young doctor substituting for his boss, the professor of medicine. During the course of the story he moves from being a careful observer (detached concern) who ascertains that his young patient has nothing wrong but a “case of nerves,” to making an imaginative leap by which he connects more deeply with her. This empathic connection allows him to relieve some of her suffering by re-framing her illness. While he cannot solve her existential problems, his demonstration of solidarity leads her to trust him and to gain insight. Korolyov is like Chekhov himself. Dr. Pavel Archangelsky, who supervised Chekhov’s first job as a physician, captured the author’s ability to listen carefully when he later commented: “… he did everything with attention and a manifest love of what he was doing, especially toward the patients who passed through his hands. He listened quietly to them, never raising his voice, however tired he was and even if the patient was talking about things quite irrelevant to his illness.” (5)  

At the other end of the spectrum, some of Chekhov’s doctors are insensitive, incompetent, or impaired. Mayer, the callous medical student in “A Nervous Breakdown” (1889) is a disaster. Mayer can rattle off statistics on the number of whores in London and Moscow, but he is unable to “see” (empathize with) the suffering of the living-and-breathing whores he encounters. Shelestov in “Intrigues” (1883) and the public health doctor in “Darkness” (1887) are examples of self-centered physicians a little further along in their professional lives. The former is superficial and pompous; the latter is narrow-minded and detached.  

Chekhov’s most complete insensitive and acquisitive social climber is found in “Ionych” (1898). Dr. Startsev, when the reader first meets him, is a young physician setting up practice in a provincial town. After surviving an unrequited infatuation with the daughter of a wealthy townsman, Startsev devotes himself entirely to work. His practice prospers and he branches out into real estate. As he grows corpulent and wealthy, Startsev loses touch with his patients (and his own humanity): 

“Probably because his throat is covered with rolls of fat, his voice has changed; it has become thin and sharp. His temper has changed, too; he has become ill humored and irritable. When he sees his patients, he is usually out of temper; he impatiently taps the floor with his stick, and shouts in his disagreeable voice: ‘Be so good as to confine yourself to answering my questions! Don’t talk so much!’” (6) 

“Ionych” traces the progressive destruction of a medical practitioner who finds that medical affluence is more to his liking than the emotionally and physically difficult path of medical virtue.  

Some of Chekhov’s most interesting doctors are tortured by existential or spiritual conflict. Chekhov accurately depicted professional burnout, a syndrome characterized by depletion, detachment, depersonalization, denial, and depression. (7) Dr. Kirilov, who chooses to “go to the office” instead of mourning with his wife, may illustrate the relatively early phase of emotional detachment. Dr. Ovchinnikov in “An Awkward Business” (1888) demonstrates the more advanced symptom of depersonalization when he slugs his assistant in response to the man’s incompetence. The overworked Ovchinnikov reacts to his personal depletion by objectifying and dehumanizing his assistant, a response that compromises the medical care he is trying to protect. Chebutykin in The Three Sisters (1900) illustrates the extreme of alcoholism. Though still employed as a military physician, Chebutykin convincingly asserts that he has forgotten all the medicine he ever learned.   

Ragin in “Ward #6” (1892) and Nikolai Stepanovich in “A Dreary Story” (1889) are complex characters in whom depression and burnout are superimposed on a deep sense of existential failure. Like many of Chekhov’s characters, these physicians suffer from a lack of self-knowledge; they move through life relying on one form of self-deception or another. When they were younger, they committed themselves to noble ideals—Stepanovich to teaching and Ragin to practice in a provincial hospital. But in the long run they never “found” themselves. Professor Stepanovich yearns for a unifying moral principle that would knit together the fragments of his life. Dr. Ragin experiences his failure as emotional numbness. He yearns to suffer, assuming that if he experienced pain, he would be freed from his inability to feel. Thus, the academic physician pines for salvation in the cognitive sphere; the practitioner yearns for emotional redemption. In each case the focus remains inward, rather than turning outward to others, in whom salvation might actually be found.  

Medical Sensibility 

Medical attitudes and methodology play a larger role in Chekhov’s work than does medical knowledge. He believed that his duty as a writer was to present his observations clearly and accurately; in other words, to lay out the data in an objective fashion and allow readers to reach their own conclusions, rather than providing an author’s interpretation. He wrote, “The artist should not be a judge of his characters and what they say, but only an objective observer.” (8) 

This objective attitude put him in conflict with most other Russian writers of the time. It was a major source of conflict with Tolstoy, who was widely revered at the time as a living saint. The two men enjoyed a close personal bond but approached writing with radically different philosophies. After his mid-life religious conversion, Tolstoy viewed literature as a way to communicate his moral vision. He preached the gospel of a radical Christianity, in which all men work together to achieve economic and social equality. However, he rejected the concept of material progress and was particularly skeptical of medicine and doctors. Chekhov, on the other hand, strove to be objective, to present people as they are and the world as it is. His medical training taught him to be a careful observer; his medical attitude made him leery of judging others.  

Other Russian writers and intellectuals spoke out against the czarist government’s repressive social institutions. While this protest was disguised in various ways in order to satisfy the state censors, late 19^th century Russians (like their 20^th century counterparts) learned to speak and understand a subtle code of insurrection. The intellectuals addressed “big issues”—democracy, education, social revolution. They wrote articles, organized meetings, and gave speeches. Here again, Chekhov found himself on a different wavelength. He rarely engaged in theoretical discussion and did not advocate radical social change. Rather, he preferred a pragmatic, case-based approach. His goals were relatively limited, but achievable. Treat the sick patient. Document and publicize the abysmal condition of prisoners. Contain the cholera epidemic. Provide financial assistance to keep farmers afloat during the famine. Raise money for a new school. On and on, but always specific and personal.  

In “About Love” (1898), the narrator speculates on the essence of love. Are there universal characteristics that identify love wherever it occurs? “What seems to fit one instance doesn’t fit a dozen others,” the narrator concludes. “It’s best to interpret each instance separately in my view, without trying to generalize. We must isolate each individual case, as doctors say.” (9) Indeed, Chekhov’s stories and plays rigorously follow this dictum. While many of his Russian contemporaries used fiction to advance moral or social theories, Dr. Chekhov focused on the complexities of human interaction. In Chekhov’s world, biology and circumstance constrain freedom. People often do not listen. Acts performed with good intentions frequently result in hurtful outcomes. And yet occasionally and in unexpected places, one finds a glimmer of love, courage, spirituality, or healing. “Never generalize,” Chekhov tells his readers. “Never theorize. Pay attention to the particulars. Focus on the concrete.” In this respect, the 19^th century physician-storyteller presages the 20^th century physician-poet, William Carlos Williams, who coined the aphorism, “No ideas but in things.”  

In the long run, Chekhov’s objectivity and aversion to theory played a major role in the development of modern literature, as 20^th century writers followed Chekhov in attempting to describe the world of human character and relationship objectively, and allowing that world to speak for itself. To the extent that Chekhov’s “lawful wedded wife” contributed to his sensitivity, skills, and attitudes, perhaps medical education and practice played an unanticipated role in the history of literature, his delightful “mistress.” 

Adapted in part from Coulehan J. (Ed.) Chekhov’s Doctors, Kent State University Press,  2003

Sir Luke Fildes’ “The Doctor,” is in the Tate: File:The Doctor Luke Fildes crop.jpg – Wikimedia Commons 

Portrait of Chekhov: File: Chekhov 1898 by Osip Braz.jpg – Wikimedia Commons 

REFERENCES 
1, Chekhov A. The Selected Letters of Anton Chekhov, translated by Sidonie Lederer, New York, The Ecco Press, 1984, p.  
2, Coope J. Doctor Chekhov. A Study in Literature and Medicine, Chale, Isle of Wight, Cross Publishing, 1997, p.  
3, Chekhov A. The Selected Letters of Anton Chekhov, translated by Sidonie Lederer, New York, The Ecco Press, 1984, p. 81. 
4, Chekhov A. A Journey to Sakhalin, translated by Brian Reeve, Cambridge, Ian Faulkner Publishing, 1993.  
5, Coope J. Doctor Chekhov. A Study in Literature and Medicine, Chale, Isle of Wight, Cross Publishing, 1997, p. 27. 
6, Chekhov A. Ionych. In: The Tales of Chekhov. Volume 3, translated by Constance Garnett, New York, The Ecco Press, 1972, p. 91. 
7, Coulehan JL. Being a Physician. In: Mengel MB, Holleman WL (Eds.) Fundamentals of Clinical Practice. A Textbook on the Patient, Doctor, and Society, New York, Plenum Medical Books Company, 1997, pp. 73-101. 
8, Chekhov A. The Selected Letters of Anton Chekhov, translated by Sidonie Lederer, New York, The Ecco Press, 1984, p. 54. 
9, Chekhov A. About love. In: The Tales of Chekhov. Volume 5, translated by Constance Garnett, New York, The Ecco Press, 1972, p. 290.

Reviews of Chekhov’s Stories

Cold Eye, Warm Heart: Medicine and Anton Chekhov  

Aug 6, 2025 6986

An Awkward Business by Anton Chekhov 

Jun 11, 2025 1980

The Grasshopper by Anton Chekhov

May 11, 2025 1812

Ionych by Anton Chekhov 

Mar 11, 2025 2994

A Doctor’s Visit  by Anton Chekhov 

Mar 11, 2025 2299

Ward No. 6 by Anton Chekhov

Mar 11, 2025 3885

A Nervous Breakdown by Anton Chekhov 

Feb 11, 2025 2093

Enemies by Anton Chekhov

Jan 11, 2025 2142

Painting an Ideal: Luke Fildes’ The Doctor with Hannah Darvin

Dec 28, 2024 1753

The Knick portrays all that goes on in and around a hospital struggling to provide care for the poorer classes in lower Manhattan during the early 1900s. It shows that many of what were then considered important advances in medicine, technology, society, and culture were later considered dangerous, unethical, barbaric, inhumane, and racist. The series asks whether health care of any era, along with associated social and cultural factors at work, are destined to be seen sometime in the future in similar ways. 

Storylines of the Poor and the Famous 

The Knick was inspired by the Knickerbocker Hospital, founded in Harlem in 1862 to serve the poor. In this twenty-part television series spread over two seasons, the fictional Knick is located somewhere in the lower half of Manhattan around 1900. The time covered during the series is not marked in any distinct way. The characters do not age much, and although fashion and customs remain static during the series, the scope and significance of advancements that come into play were actually adopted over a longer time than the episodes cover.  

The series builds on some known history. The central character, the chief surgeon Dr. John Thackery, is modeled on a famous surgeon of the time, Dr. William Halsted, in both his surgical adventurism and in his drug addictions. The character, Dr. Algernon Edwards, who is an African-American, Harvard-educated, and European-trained surgeon, is based in part on Dr. Louis T. Wright, who became the first African-American surgeon at Harlem Hospital during the first half of the twentieth century.   

Storylines of human drama and folly run through the series. Among them are medical cases both ordinary and bizarre, heroic successes and catastrophic failures, loves won and lost, gilded lives and wretched existences, honor and corruption, racism and more racism. Within these storylines are the scientific, medical, and industrial advances of the period, as well as the social frameworks that form fin de siècle hospital care and medical research in New York City.   

Some of the industrial advances adopted by the hospital include electrification, telephone service, and electric-powered ambulances. We see that transitions to these new technologies are not without risks and catastrophes: patients and hospital staff are electrocuted, and when the ambulance batteries died — a frequent occurrence– many of the patients they carried died, too. 

Medical advances integrated into various episodes include x-rays, electric-powered suction devices, and an inflatable balloon for intrauterine compression to stop hemorrhages. Thackery is a driven researcher taking on some of the big problems of the day, such as making blood transfusions safe, curing syphilis, and discovering the physiologic mechanisms of drug addiction. We see how he learns at the cost of his patients, or rather his subjects. We also get a glimpse of movements directed at population health. For example, epidemiological methods are applied to find the source of a typhoid outbreak, which drew from the actual case of Mary Mallon (aka, Typhoid Mary). Shown juxtaposed to the advances in epidemiology is the concurrent interest that was rising in eugenics and its broad application to control for unwanted individual traits and particular groups of people. Research ethics and regulations were a long way off.  

Time Tells 

Each era possesses its own hubris based on the technological advances and social progress made over those of previous eras, and on the certainty that the mistakes made before have not been repeated. Time reveals whether those attitudes and positions were justified. For Soderbergh, the director of the series, this idea was top of mind, and he stated as much in an interview published in the August 1, 2014 New York Times:  

There are so many treatments on the show that make you gasp because they’re so wrong…It just makes you wonder what treatments we’re all taking at face value that 10 or 15 years from now we’re going to be told, ‘Well, that didn’t work, and in fact that makes it worse.’  

Early twenty-first-century medical care has benefited from advances in molecular biology, medical devices, surgical procedures, data analytics, and epidemiological methods among others. People only participate in experimental protocols with their informed consent, and health care workforces are highly diverse. Impressive indeed, but none that in any way dwarf some of the advances shown during the series, and many that make twenty-first-century medical care possible. And, while The Knick shows how patients were often victims of bad science, bad technique, unproven technology, and malfeasance, the current era of health care is rife with risks for its own harms. Based on a complex analysis from several sources, the U.S. Institute of Medicine estimated in 1999 that between 44,000 and 98,000 people die from preventable medical errors each year in the US (To Err is Human). In 2016, researchers from The Johns Hopkins University reported in the May 3, 2016 issue of The BMJ (The British Medical Journal), that at the time The Knick was running in 2014–2015, medical errors were the third leading cause of death in the U.S. While the the accuracy of these estimates could be challenged, we can take from them with some amount of certainty that medical error exists today to a significant degree.  

The Knick pushes us to consider and to beware of what we may see resulting from modern-day biomedical and technological advances as time passes. To the medical drama and personal drama of most television medical serious, The Knick adds the drama of time. 

—————————- 

The Knick
Steven Soderberg, director 
Cinemax 
Twenty episodes, 2014-2015 
Running time: 42–57 minute episodes 

Awards
Peabody Award 
Six Primetime Emmys 
Three Critics Choice Television awards 

The Knick began streaming on HBO Max on February 20, 2021 

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

In Dangerous Medicine: the Story behind Human Experiments with Hepatitis, Sidney A. Halpern tells the story of America’s decades-long investment in hepatitis inoculation experiments, of which the infamous Willowbrook study was only the final and perhaps most egregious example. The experiments began in 1943 in response to an epidemic of “serum” hepatitis among military draftees who had received yellow fever vaccine. The initial idea was to characterize the infectious agent that caused the disease and to examine its clinical features under controlled conditions. In later years, studies involved testing various preventive measures, both for serum (B) and infectious (A) hepatitis.  

During World War II, the Armed Forces Epidemiology Board (AFEB) initiated a series of inoculation studies among conscientious objectors, prisoners, and mental patients. Most of the subjects were conscientious objectors who volunteered, despite having a wide variety of service options. “Virtually all the men serving as hepatitis subjects spoke of a desire to engage in meaningful and consequential humanitarian service.” (p. 63) Investigators told the volunteers, “It is our judgment that the possibility of permanent or even protracted or severe impairment of liver function following participation in the jaundice experiment is very slight.” (p. 48) At that time, of course, long-term consequences of hepatitis B infection—chronic infection, cirrhosis, and hepatocellular carcinoma—were unknown. However, many of the subjects did develop clinical disease and at least one subject developed fulminant liver failure and died.  

After the war, hepatitis researchers relied almost exclusively on institutionalized subjects. For example, Joseph Stokes Jr. of the AFEB “not only drew subjects from a mental hospital and multiple institutions for children, but he also enlisted inmates from five state correctional facilities… in New Jersey.” (p. 101) Stokes claimed the research was “beneficial for both the facility and its residents.” (p. 96) Later, researchers at Johns Hopkins, Yale, and the NIH conducted studies at other institutions. For prisoners, participation offered multiple benefits, including the possibility of early release. Among the objectives of studies during the 1950s were attempts to eradicate the infectious agent by sterilizing the infected serum, which were unsuccessful. During these studies, four subjects died of fulminant hepatitis, two at McNeil Island Penitentiary in Washington and two at Lewisburg Penitentiary in Pennsylvania.  

Willowbrook was one of two long-term hepatitis inoculation programs begun in 1956. At the time, Willowbrook State Hospital on Staten Island had one of the largest populations of the cognitively impaired in the USA. It was the overcrowded home to some of the state’s most disabled patients – 39% were non-ambulatory, and 64% unable to feed themselves. A New York University team, later headed by Saul Krugman, professor of pediatrics, established a hepatitis unit which each year admitted approximately forty-eight children between three and ten years of age. Many of the experiments involved injecting subjects with serum containing live infectious (A) or serum (B) hepatitis virus. Major study findings included clearly distinguishing between the natural history and characteristics of hepatitis A and B, and discovering that gamma globulin was an effective means of preventing clinical illness in hepatitis A. 

This decades-long sequence of inoculation studies occurred despite post-war developments in research ethics. The Nuremberg Code was promulgated in 1947, followed in 1964 by the Helsinki Declaration. These documents established principles designed to protect the rights and welfare of research subjects, including respect for individuals, voluntary participation, informed consent, risk/benefit analysis, confidentiality, and scientific integrity. However, at least in the United States, hepatitis investigators, among others (e.g. Tuskegee syphilis study), ignored or evaded these principles.

Except for wartime experiments on conscientious objectors, hepatitis inoculation studies violated almost every ethical principle set forth in the Nuremberg Code and Helsinki Declaration. The vast majority were conducted in closed institutions among subjects who either lacked the ability to consent, or whose participation was not necessarily voluntary (i.e. prisoners). Where consent was obtained (e.g., from a prisoner or surrogate), the investigators provided incomplete or false information (e.g. stating that risk was minimal), despite several deaths from fulminant liver failure. Yet, Joseph Stokes claimed that virus inoculation could “in our opinion be of benefit to the individual himself.” (p. 98) In addition, coercive tactics were used (e.g., quicker admission to an institution, or earlier release from prison).  

Dangerous Medicine highlights unethical practices in American hepatitis research throughout the mid-20^th century. While contemporary ethical standards had yet to be established, broad ethical principles articulated by the Nuremberg Code and Helsinki Declaration and reiterated (at least, in part) by the American Medical Association, were ignored. Public outcry in 1972 against Willowbrook, Tuskegee and other unethical research led in 1974 to the establishment of the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research and, subsequently, to the Belmont Report, the Common Rule, Institutional Review Boards, and contemporary standards in human subjects research. Interestingly, as far as Dr. Halperin is aware, no follow-up studies have ever been done to ascertain the long-term health consequences of these hepatitis study subjects.  

Dangerous Medicine tells a sobering story, well-worth reading. And, given the prevalence of academic incentives and multiple conflicts of interest, I’m afraid the story of unethical research is far from over 

1. Beecher HK. The Ethics of Clinical Research. New England Journal of Medicine. 1966; 274: 1354-1360. 

Dangerous Medicine: The Story behind Human Experiments with Hepatitis
Sydney A. Halpern
Yale University Press, 2021
304 pages 

Web image of Hepatitis B from Wiki Commons