Pharmakon
Notes from a Family Meeting, Vol. 2, No. 6
I will be your pharmakon
Keep you well when day is young
Light your life just like the sun
Steal your breath when day is done
Love like a poison
September is going, going, goneI will be your remedy
Bring you up and help you see
Hold you close then set you free
Promise what I cannot keep
Buried deep is a quiet seed
Winter comes and all the small creatures sleep
Pharmakon by Humbird
When I was in medical school, I transformed my lectures into pages and pages of charts. Most of the information we were learning could be bound into the rows and columns of my organized, color-coded charts. Pharmacology lent itself very nicely to this method, with columns for indications, metabolism, adverse effects, and all the other minutiae we were learning. I spent hours with those charts. It wasn’t until I had gotten to residency and spoke pharmacology like a second language that I began to stumble over some hidden qualities of the medications I prescribed. It’s not that my pharmacology classes were wrong, but they didn’t tell the whole story.
I saw that medications, and really all medical interventions, carried hopes and fears. They could stigmatize and normalize. They were heroes and villains. They could lift burdens and impose them. They could hold terrible diseases at bay and render financial ruin. More often than not, “and” was the right way to see these things, not “or.” That’s what the old Greek term “pharmakon” means - both remedy and poison. It’s the ambiguity that makes the pharmakon so bedeviling and unwieldy. Its behavior in the real world always evades our expectations, for good or ill.
I encounter the pharmakon daily in my practice as a palliative care physician. When I first meet people, I explain that I do two big things: I help folks with anything that bothers them (pain, nausea, sleep, etc.), and I also support them and their families going through the tough times of serious illness and the complicated medical decisions that can arise. Many of the symptoms I manage are fallout from other medical interventions.
Adverse effects of medical intervention are the most obvious manifestation of the pharmakon in clinical medicine. The surgery that saved someone’s life has left them with chronic pain. The chemotherapy targeting someone’s cancer wracks them with nausea. The steroid intended to reduce inflammation electrifies sleep with anxiety. These are the trade-offs we need to consider when trying to discern if a particular intervention will help someone pursue their goal of care.
But the pharmakon brings still other boons and burdens. Asha Persson described the social ramifications of lipodystrophy, a well-known adverse effect of some antiretroviral therapies for HIV. While patients need the medication to survive, lipodystrophy afflicted them with the stigmatized marks of HIV, an otherwise “hidden” illness. Persson wrote:
“For all their innocuous appearance, every pill is a potent fusion of ingredients, including scientific practices, political agendas and commercial interests, along with social activism and media spin. Medicines, therefore, are more than merely chemical compounds; they are cultural entities. As such, they are products of human culture, but also producers of it, affecting people’s sense of being and social lives as intimately as food, money and other charged ‘things’.”
The psychosocial impact of antiretroviral therapy exceeds the biomedical lens most clinicians use to assess the effect of their prescription. This means the pharmakon sneaks around the clinical encounter and patients’ lives without the experts seeing it.
In my line of work, this comes up not uncommonly when patients are concerned about being perceived as (or actually becoming) someone who abuses opioids, particularly if I recommend methadone for pain. The medication carries more psychological weight than the physiologic risk actually entails, for the risk of opioid abuse is low when these are appropriately prescribed, taken, and monitored. These medications don’t just relieve pain, then, but are powerful entities capable of changing one’s behavior, relationships, and even identity.
Sometimes the promises of a medication are almost entirely illusory, like a substance given in a phase 1 cancer trial. A phase 1 trial is quite literally an attempt to discern at what dose this substance becomes poisonous. There is no therapeutic intention, but many patients sign up for phase 1 cancer trials with the hope they might benefit. It’s not only that patients need treatment for their cancer, but they also need the hope afforded in the offer of continued treatment. Hope is the siren’s call of the pharmakon. Even if the substance in a phase 1 cancer trial isn’t at all therapeutic, the concrete hope of cancer treatment swells to match the burden of enduring the trial protocol.
We find another example of the pharmakon in masks and vaccination during the COVID pandemic. A physical barrier intended to reduce the risk of transmission and infection of this virus has become a hyper-polarized shibboleth (to use another ancient word). An inoculation of what is essentially the fingerprint of the virus has become the same, despite vaccines being one of the medical marvels of the twentieth century responsible for saving countless lives. These are now more than a mere medical interventions; in some parts of the United States, they’re political statements, and serve to form the culture in particular ways, both in their presence and their absence. Masks and vaccines have identities that no one can now control, despite their best attempts at education and explanation. Ironically, the more one tries to explain that these are merely a medical interventions, the more entrenched some might become in believing otherwise. Attempts to dispel disinformation, misunderstanding, or anxiety show that we don’t really see the whole picture; we’re missing the pharmakon again, even though we’d disagree with that assessment. This isn’t an apologetic for the anti-mask/anti-vaccine camp. I only want to highlight how the work of the pharmakon can divide communities as people come to feel the impact of interventions differently. The power of the pharmakon can’t be overcome with education. Where education fails, we think coercion might work. And if the aim is to simply get vaccines in people’s bodies, coercion does work to a certain extent, but it still won’t overcome the formative work of the pharmakon.
The pharmakon doesn’t just affect patients. Clinicians use therapies with the earnest hope that their patients will benefit. They become the primary means through which clinicians demonstrate that they care. When that happens, the insidious poison of the pharmakon can get to work, convincing them that these therapies are the only means of caring. As palliative care physician Diane Meier noted, this can lead to over-treatment as clinicians see treatment cessation as abandonment. The act that once provided remedy can both harm the patient with over-treatment and harm the clinician by atrophying their compassion. Not that they aren’t compassionate in the first place, but they forget how to be compassionate in the absence of ceaseless prescribing or operating.
Nor does the pharmakon only manifest in medical interventions like medications and surgeries. Communication in the clinical encounter is a pharmakon. The words a clinician speaks intending to convey important information may also harm via viscerosomatic amplification (wherein the words themselves actually exacerbate symptoms). The very same words that convey compassion may create the suffering that calls for that compassion. The very same words that convey one type of hope (e.g., that someone will survive) may take another hope away (e.g., that they’ll be able to walk again). The words that offer a choice may create a condition in which it would have been better to never have chosen at all.
The pharmakon is everywhere. It’s inescapable.
Handle with Care: The Pharmakon and You
Recognizing that most of the things we do in medicine have the spirit of the pharmakon within them, what can we do? It’s not as easy as just avoiding them, for in so doing, we would forsake our work altogether. We also can’t educate ourselves away from its thrall. Its effects are too wide-ranging, too formative, too subtle, and not entirely rational to begin with. Education about the adverse effects of a drug might help us approach its use eyes wide open about the risk of taking it, but it won’t help us resist the culturally formative impact of how, say, psychotropic medications make us see ourselves.
Neil Postman, writing about technological change in 1998, offers a guide here centered on humility and honesty. He had five observations that I’ll use here to frame how we might think about handling the pharmakon:
“All technological change is a trade-off.”
I’ve discussed trade-offs before when regarding the goals of care and how to talk about them. Nearly every medical intervention comes with a trade-off, even if it’s vanishingly small - like the burden of remembering to take folic acid every day, which is seemingly minor when compared with a the possibility of a neural tube defect in a child. The language of trade-offs is a straightforward and humbling way to acknowledge that our attempts to help often impose their own burdens, whether annoying or crushing. These trade-offs aren’t just physiologic, but can be financial, psychological, and social too. What are the trade-offs in using the medical intervention you’re considering?
“Advantages and disadvantages of a new technology are never evenly distributed among a population. … new technology benefits some and harms others.”
So, too, it’s humbling to recognize that our medical interventions are unjustly offered more frequently and with greater success to some than others - many have written about the inequities in healthcare. It’s also true that the spirit of the pharmakon will affect people differently. Some will derive more hope or less, be more or less impacted by the lipodystrophy of antiretroviral therapy, or be more or less stigmatized taking a D2 antagonist for psychosis. Scientific trials can give us an idea of how things will go when we use a particular medical intervention, but the epistemic leap from general evidence to particular patient is a leap indeed. This is a wicked problem. Even if we ironed out all the inequities due to ethnicity, socioeconomic status, sex, age, and so on, the pharmakon would still befall people in different ways due to its very nature: its cultural identity might change in different cultures, its psychological impact might change depending upon the psychology of the one who handles it, and so on. Scientific development in medicine tempts us to speak of medical interventions as if they’re as generalizable as laws of nature. Instead, recognizing the power of the pharmakon, we should avoid speaking of medical interventions as if they’re monolithic. What’s unique about this situation that could make the medical intervention you’re considering do unexpected or unintended things?
“Every technology has a philosophy which is given expression in how the technology makes people use their minds, in what it makes us do with our bodies, in how it codifies the world, in which of our senses it amplifies, in which of our emotional and intellectual tendencies it disregards.”
Medical technology is more than a mere collection of tools. It’s even more than a lens through which we see the world. It shapes how we think through its reductionism and its promises. Of course we want to believe that we’re helping when we deploy medical technology upon someone else’s life, for it’s unfathomable to believe that the opposite may be true: that sometimes the best uses of chemistry, plastic, and electricity are harmful, in both obvious and subtle ways. If we call everything we have a “therapy,” then none of it is ever a poison, which belies the reality of the pharmakon. Medical technology has an agency of sorts. It behaves in ways we can’t always predict nor that we intended when we used it. Perhaps agency isn’t the right word; I’m open to suggestions here. Nevertheless, the relationship between people and medical technology isn’t always one of user and tool. The relationship is bidirectional, complex, formative, and fluid. If we behold this agency, then we might grow in respect for this unknowability and its power. If you think of a medical intervention you commonly use, how might you understand it to possess some of this kind of agency?
“Technological change is not additive; it is ecological. … A new medium does not add something; it changes everything.”
The twentieth century witnessed amazing developments in medicine. Consider something like the ventilator. Before the ventilator, untold numbers would die from respiratory failure. After the ventilator, we didn’t just have one more tool in the toolbox; we had a whole new world of medicine. The intensive care unit revolutionized the world, and with it, how we think about dying. It also came with the hidden barb of chronic critical illness - something no one could have predicted. The power of the pharmakon is best seen as ecological in this sense: changing culture, changing perspectives, twisting in our grip and doing something unexpected. Not every new medical technology has such wide-ranging impact, but to the extent they don’t, it’s probably because they’re modeled on previous technologies that did. Chlorpromazine (Thorazine) revolutionized the treatment of psychosis. The seemingly endless development of its D2 antagonist grandchildren, each offering some incremental change, has been less-than-revolutionary. In what ways is the medical intervention you’re considering reaching beyond its individual use to impact the broader community and culture around you and your patient?
“Media tend to become mythic. … a common tendency to think of our technological creations as if they were God-given, as if they were a part of the natural order of things.”
The thing with revolutions is that, when successful, they become a new regime responsible for maintaining the new status quo. As revolutionary as its development was, It’s hard for those in the developed world to imagine clinical medicine without the ventilator, which is one among numerous reasons why the pandemic has struck such a demoralizing blow - we have, at times, found ourselves without this pillar of critical care medicine. COVID has shaken us from the dream that the ventilator is a given; that it’s burdens and benefits are just the usual business of critical care medicine. Short of catastrophe or very persistent and often unpopular research, mythical medicines are very difficult to interrogate. Isn’t it obvious that knee arthroscopy should help osteoarthritis? It turns out it doesn’t, but that was the conventional wisdom for years. This helps the pharmakon evade detection. However, the risk of simply questioning all the givens around us is, at the extreme, distrust for the institutions that make our work possible. How can we investigate the pharmakon without totally disrupting our institutions? Or is total institutional disruption what’s required in order to understand and handle the pharmakon well?
Perhaps I’ve left us with more questions than answers. I think that’s a good idea when facing the pharmakon. The right questions matter as much or more than the answers we gather, because the questions set the frame for our inquiry. Some questions are never fully answered and we wrestle with them throughout our lives. That wrestling is more impactful than any easy answer we might wish we had. Maybe it’s in such wrestling that we’re able to more carefully see and handle the pharmakon, even if there are no easy ways to do it.
Trajectories
Following a meandering reading-path, sharing some brief commentary along the way.
“Prognostication in advanced cancer: update and directions for future research”
A helpful review from a couple years ago on the latest evidence regarding prognostication. Unfortunately, it doesn’t address a holistic prognosis (except in covering toxicities of systemic therapy, insofar as that would relate primarily to symptoms). Nevertheless, a good review of the data out there related to life expectancy and cancer.
“Phase I cancer trials: a collusion of misunderstanding”
This piece is older, so it doesn’t take into account the immunotherapy revolution in oncology. Nevertheless, many of the concerns remain valid because phase I trials in oncology remain laden with therapeutic misperception. Most phase I trials enroll healthy volunteers, but in oncology, the thinking is that, given that the medications have such a high risk for toxicity, only patients with cancer enroll - and those who have been extensively pre-treated. The point of the trial design is to find a safe, tolerable dose of the drug, not to induce a therapeutic response. But the vast majority of patients hope that the drug will help them individually (Miller cites that < 1% of patients benefit; an updated review from 2020 indicate the response rates are better, particularly among immunotherapy, but keep in mind that a surrogate response rate doesn’t necessarily correlate to clinical benefit). Miller found that he could only navigate this problem if he explained, in detail, how his relationship with patients as a researcher was different than that of a clinician, and the purposes of phase I research.
“Problems: Philosophical and historical exploration of why we spend so much time on notes.”
Adam Rodman is the host of the wonderful Bedside Rounds podcast, exploring the history of medicine. In this grand rounds lecture, Rodman traces the path of medical documentation throughout history, arguing that how we write is how we think. The latest iteration of documentation has been Larry Weed’s “problem-oriented medical record” and the “SOAP” note, which was in reaction to the incomprehensibility of medical records at the time. Ironically, we now encounter the bloated chart that, while being technically problem-oriented, is almost as incomprehensible. These notes don’t help clinicians think about their patients, despite how much time clinicians spend on them. This also has humanistic ramifications: if you spend years describing patients as the “50 year old female with cholecystitis,” and proceed to write a pathophysiologic narrative about this female, then you will see people in this way: as mere physiology. Rita Charon’s counter to this within the realm of narrative medicine is a shadow chart in which clinicians can write about the other aspects of the clinical encounter, but realistically only a fraction of clinicians will do this. How can we improve documentation to better humanize not only patients but also the clinicians who are writing?
“It’s misleading to call addiction a disease”
Carl Fisher, a psychiatrist and in recovery himself, wants us to look beyond the limited medical paradigm of addiction: “I believe that waking up to addiction is a tremendous gift, because it points us toward universal human struggles with self-control and working with our pain. In that sense, addiction is profoundly ordinary, contiguous with all of human suffering. We cannot end it, we certainly cannot cure it, and medicine alone will never save us. But if we drop the idea of disease and open up to a fuller picture of addiction, it will allow for more nuance, care and compassion.” Certainly the disease model of addiction has done a lot of good in de-stigmatizing the plight of those who struggle with these things. When we reduce it, like almost any other disease, to mere pathophysiology, we’re bound to miss some things.
Writing of the tension between tending to the iPatient in the electronic medical record and the real patient to whom we’re actually beholden, Abraham Verghese exhorts, “It is a one-word rallying crying for patients and physicians, the common ground we share, the one thing we should not compromise, the starting place to begin reform, the single word to put on the placard as we rally for the cause. Presence. Period.” So much threatens to erode the presence clinicians have with their patients, and presence doesn’t always promise quick results. Building a relationship isn’t a speedy endeavor. So being steadfast and present is an exercise in trust as much as compassion. We have to trust that, through our presence as well as through our technique, we can help this other person.
Closing Thoughts
“There is no reason whatever to assume that the languages of science are less limited than other languages. Perhaps we should wish that after the processes of reduction, scientists would return, not to the processes of synthesis and integration, but to the world of our creatureliness and affection, our joy and grief, that precedes and (so far) survives all of our processes.“
Wendell Berry, Life is a Miracle