Introduction

Daniel R. George

Since the 1990s, the United States has seen a precipitous rise in Deaths of Despair (DoD), defined as mortality resulting from suicide, drug overdose, and alcohol-related liver disease (Case and Deaton 2015). While these despair-related deaths were first noted in 2015 among rural working-class white adults with low educational attainment in midlife (see Fig. 1), they have more recently extended across racial, ethnic, and gender lines, as well as into cities and suburbs (Woolf et al. 2018; Brignone et al. 2020; George et al. 2021; Friedman, Hansen, and Gone 2023), in part due to the influx of fentanyl in the US drug supply.

Fig. 1
figure 1

On the left: US death rates for whites began to rise around 1995, whereas rates in other wealthy countries have continued to fall. Major causes across ages are Deaths of Despair. On the right: Deaths of Despair rise steeply among successively younger birth cohorts. Thus, the cohort born in 1970 (upper red arrow) reaches 100 deaths/100,000 by the age of 45 (lower red arrow), but the cohort born in 1985 (upper red arrow) hits that mark by age 30 (lower red arrow; only one data point is shown). Both tables are redrawn from Case and Deaton (2017) and reprinted, with modifications, from Sterling (2020)

Full size image

Deaths of Despair have emerged out of a specific set of historical conditions. Rates of despair-related mortality are disproportionately higher in economically distressed regions—particularly areas like the Rust Belt Midwest and South that have been aggressively reshaped by post-1970s neoliberalism (e.g., globalization, free trade, privatization, deregulation, austerity, de-unionization, etc.), as well as technological shifts (e.g., automation and robotics). Tellingly, the primary predictor of risk for a despair-related death is the lack of a college degree (Case and Deaton 2020). In a post-industrial economy that has largely shifted to service-, knowledge-, and gig-economy labor, it appears increasingly difficult for Americans with low educational attainment to establish strong job prospects and stable incomes.

The gradual decline in material conditions for the US working class has engendered a corresponding degradation of community bonds, shifting family structures, and growing loneliness, isolation, and social dislocation. For many, these transitions appear to be increasing a desire to numb, escape, or make more bearable the pain of modern life. Into this milieu of widening despair has flowed prescription painkillers and other lethal synthetic opioids/tranquilizers (heroin, fentanyl, xylazine, isotonitazene), cheap and accessible alcohol, and rising rates of gun ownership, all of which have contributed to excess mortality. Indeed, despair-driven deaths have historically been highly sensitive to economic volatility, political instability, and rising psychosocial stress. In the 1990s, after the fall of the Soviet Union and the rapid neoliberal reordering of the country’s economy, Russia experienced 7.3 million excess deaths and an unprecedented fall of six years in mean life expectancy, with the largest contributions from rising levels of suicide, alcohol, and illicit drug consumption (King, Scheiring, and Nosrati 2022). In the US, the worsening domestic crisis has only been further exacerbated by the socioeconomic shockwaves of the COVID-19 pandemic. In 2020, a record 186,763 annual DoD were documented (Trust for America’s Health and Well Being Trust 2022), with annual despair-related mortality contributing to the longest sustained decline in US life expectancy since 1915–1918 (Arias et al. 2022).

Humanities scholars and social scientists are well-suited to engage with this era-defining public health catastrophe. Action on DoD has been paralyzed by an unresponsive political system, overreliance on biomedical frameworks, and culture war tendencies to distract, scapegoat, and divide rather than solve social problems. In contrast, humanists and social scientists are more able to address and illuminate suffering, including identifying the root causes and structural drivers of the DoD crisis. The health humanities, that is, can contextualize the phenomenon of despair-related deaths both within the more recent history of political-economic assaults on the humanity and material well-being of workers and the working poor in these communities and with respect to the broader human condition.

In this forum feature, three essays model how health humanities frameworks can help us interpret and act vis-à-vis the DoD catastrophe. Political scientist and philosopher Benjamin Studebaker examines how ideas from ancient and contemporary philosophy, political theory, and social science can contribute to our thinking about the age-old challenge of meaningfully integrating people into society. He explores the DoD crisis through what he refers to as the “Five A’s” (anomie, alienation, atomization, anxiety, and absurdity), factors that are perhaps intrinsic to the human condition but which have converged in the neoliberal era in especially deleterious ways to drive despair-related mortality and morbidity. Dr. Studebaker further draws upon perspectives from Plato, Durkheim, Marx, Polanyi, and others to imagine how wiser statecraft could buffer against despair and protect those who might otherwise be set adrift amidst the dispossession, discontentment, and so-called creative destruction of modern global capitalism.

Neuroscientist and anthropologist Peter Sterling follows with an essay arguing that contemporary biomedicine, with its reductionist tendencies, is “hopelessly flawed” in dealing with the worsening DoD crisis. He offers a perspective informed by evolutionary anthropology that establishes a dialectic between human biology and cultural context. As with Dr. Studebaker’s essay, the humanities lens applied by Dr. Sterling enables us to see pathways through which contemporary societal structures are quite literally engineering despair, anomie, and ill-health and also exposes the folly of seeking molecular fixes to crises that exist at the level of population health.

Lastly, medical sociologists Megan S. Wright and Cindy L. Cain argue that health humanities scholars must engage with the lived reality of despair and humanize the static and emotionally sterile epidemiologic narrative that has predominated in mainstream discourse. In thinking upstream of the overwhelming annual numbers of despair-related deaths, they argue that we in humanities disciplines must tell the stories of those suffering in the 2020s, examine the structural failures driving social determinants of their despair, and think about solutions across systems.

Together, these essays offer powerful insights into the causes of and potential solutions to despair-related illnesses. My goal with this forum feature is to challenge humanities scholars to address this contemporary catastrophe and jump-start health humanities research in this domain, which urgently needs our attention and action.

Five sources of despair

Benjamin Studebaker

In the US, the Deaths of Despair crisis is often discussed in cultural terms. Liberals tend to point out that the crisis disproportionately affects white men and use this to argue that it is caused by anxiety about a potential loss of social privileges (Boyd 2020; Metzl 2019). Conservatives tend to frame the same situation as a crisis of masculinity or as a symptom of decadence (Peterson 2018). These approaches converge in framing despair as an education problem. They suggest that despairing citizens just need to be taught to think the “right” way about cultural issues. They suggest that despair is just a mistaken attitude, something to be managed largely by public schools, religious organizations, and psychologists and otherwise addressed in the form of individual self-help.

But political theorists and sociologists have long understood that despair has deeper roots in both the human condition and the economic organization of societies. When people are not integrated into society effectively, they become deeply dissatisfied with their lives. Plato points out that when citizens lack meaningful social roles, their frustration can lead to violence. For Plato, as economic inequality increases and the rich purchase the property of the poor, the dispossessed become “drones” with no clear role in their cities. These drones are divided into “stingless drones” or “beggars” and drones “with stings” who become “evildoers” (Republic 552c–d). Plato does not just worry about drones. He also worries that social roles might be misallocated and that some citizens may end up in roles that do not suit them. For Plato, the proper fit of one’s role is so central that he goes as far as to define justice as “doing one’s own work and not meddling with what isn’t one’s own” (Republic 433a–b). When this principle of specialization is broken, it produces civil conflict, as citizens fight with each other over who gets which roles. Plato even writes that “civil war” is “always and everywhere ‘of this lineage’” (Republic 547a).

These two problems—having no role and having the wrong kind of role—are expressed again in the works of Émile Durkheim and Karl Marx. Durkheim, a French sociologist who wrote in the late nineteenth and early twentieth centuries, argues that economic problems “have an aggravating effect” on the suicidal tendency because, when people lose their jobs or find themselves in dissatisfying jobs, they lose their sense of purpose and direction (Durkheim 2005, 201). He writes that when “the workman is not in harmony with his social position … he is not convinced that he has his desserts” (211). Durkheim also applies this analysis to the family, arguing that suicide becomes more likely both when widows lose their spouses and when people get divorced (220–25).

Marx, for his part, argues from the perspective of political economy that social roles become alienating when the goals of the role and the goals of the person performing the role become estranged (Marx 1844). A cobbler designs and assembles shoes and does so for the purpose of making high-quality shoes that are of value to society. But if that cobbler is reduced to working on an assembly line in a shoe factory, the relation to the object of one’s labor changes. Line workers are not asked to think about what kinds of shoes are best. They do not design shoes, and they do not craft them. Instead, they perform a small role in the shoe-making process. The purpose of the process is to produce high-quality shoes that are salable in the market. But because the line worker is only superficially making shoes, they perform the job largely for the purposes of obtaining a wage with which to secure a means of subsistence. The shoe factory provides the worker with a role, but it is an unsatisfying role in which the worker’s creative capacities are stifled and eventually atrophy. This dissatisfaction generates instability.

Durkheim and Marx associate these forms of social malaise with modernity or with capitalism. Industrializing societies are changing quickly. They create and destroy roles more frequently and in larger numbers. They subject more people to a loss of role, and decentralized markets often create roles without fully considering whether those roles will be appropriate for the specific people inhabiting them. Political theorists have always had to worry a bit about changes in the way roles are allocated, but in modernity and under capitalism, these changes occur more frequently, with less time to plan them out and help citizens adapt.

Karl Polanyi (2001) argues that as the market system develops, it puts greater pressure on people. Competitive labor markets make it easy to fire employees. Efforts to fight inflation restrain wage growth. The growth of international trade can expose workers to competition over their jobs and reduce their leverage with their employers. The need to earn enough to keep a stable life forces people to work longer hours, leaving less time and energy for other activities outside of work. For Polanyi, these changes necessitate state intervention. Otherwise, the market system undermines the social system necessary to maintain the market system in the first instance.

When the state fails to act, the market system dominates increasing areas of social life, causing further disruption to social roles. Contemporary American political scientist Robert Putnam (2000) points out that, over the past 70 years, there has been a marked decline in group membership in the United States. When too much time and energy is taken up with work, there is not much left for participating in other activities. In the twentieth century, Americans who were not wholly satisfied with their jobs might nonetheless have avoided despair by joining civic organizations of various kinds. But there is less time and energy available for these clubs now. In recent years, new technology—the internet—has combined with the COVID-19 pandemic to further eliminate opportunities for meaningful in-person interactions, thus reducing the “buffering” effects these social connections have on individual well-being.

This also affects people who might otherwise like their jobs. Many people who do creative work in the twenty-first century do much of this work remotely. They interact less with colleagues, which can diminish the degree to which they feel their work is meaningful. Fewer opportunities to interact in person make it harder for people to build family structures of both traditional and non-traditional varieties. Even when average citizens are able to construct families, weak wage growth makes it hard for families with children to keep a parent at home, pushing them to pay for childcare, further increasing their expenses, and making it even more important that they work more hours (Hodge and Lundeen 2013). The financial stress causes many families to fight about money, which can, in turn, lead to divorce, diminished access to one’s children, and the loss of filial roles that are important to well-being (Ragusa 2021).

Even when people have roles that they like and are sufficiently social, they have to worry that their situations might change sooner than they think. When there is rapid change and roles are flippantly created and destroyed, no one can be sure their role is safe. Americans worry that they might lose their jobs, they might keep their jobs but lose their pensions or health insurance, their jobs might change in upsetting ways, they might be forced to move to another city or another state for work, or their businesses might fail. Even if these things never happen, the fact that there is a lot of technological and economic growth and that the state cannot be relied upon to cushion the volatile actions of the market generates endemic anxiety about the future. Albena Azmanova argues that in recent decades there has been a “universalization of insecurity” and that the “majority of the population” is affected by this, “almost irrespective of employment type and income level” (Azmanova 2020, 2).

Some Americans do not have roles, some have roles that do not suit them, some have roles that leave them socially isolated, and some fear that they will lose good roles. On top of all this, the feeling that these problems cannot be overcome politically itself produces feelings of despair. The late Peter Mair—an Irish political scientist—argues that voters increasingly feel they have been left with: “What is still called democracy, now redefined so as to downgrade or even exclude the popular component” (Mair 2013, 15).

Mair suggests this produces more irregular voting behavior. Creeping fatalism makes voters feel their electoral choices do not matter much, so they start disengaging or voting flippantly. As he puts it, there are “more and more citizens who, when they think about politics at all, are likely to operate on the basis of short-term considerations and influences … a form of voting behavior that is increasingly contingent, and a type of voter whose choices appear increasingly accidental or even random” (Mair 2013, 42). Mair’s voters feel that the political system is radically unresponsive to them. The political system begins to seem absurd. If political action does not appear effective, it can either be a waste of time or a source of entertainment. Voters in this situation stop taking politics seriously, adopting a nihilistic, absurdist attitude toward it.

In this piece, I have described five different distinct problems with social roles that can plausibly lead to despair:

  1. 1.

    Anomie: the lack of a social role in the first instance and the feelings of purposelessness that accompany this.

  2. 2.

    Alienation: the sense that one is in the wrong role, roles have been misallocated, and one’s role frustrates the development or use of one’s capacities.

  3. 3.

    Atomization: the sense that, even if one’s role is otherwise acceptable, it provides insufficient opportunities for social interaction and the feelings of loneliness that accompany this.

  4. 4.

    Anxiety: the fear that, even if one has a role that is acceptable in some or all respects, it is not secure against future socioeconomic changes.

  5. 5.

    Absurdity: the feeling that the whole political and economic system is out of tune, it does not respond to human values, and it is pointless to engage seriously with it.

Taken together, we can call these “The Five A’s.” The Five A’s can, of course, appear together. Sometimes a person feels alienated and atomized at the same time. Sometimes a person is alienated and atomized but still anxious about losing their role and being plunged into outright anomie. The feeling that the system is absurd often comes out of the current or past experiences of the other A’s. If we were to argue that the despair crisis is caused by just one of these factors, that would not be quite right. It is likely that they all interact with one another.

A person experiencing The Five A’s may be looking for individuals or groups to blame for these experiences. Cultural antagonism may itself be caused by The Five A’s, as people try to make sense of their situations by constructing enemies to account for why things feel so dire. When someone in despair blames cultural enemies for their circumstance, this does not mean that the culture war is, in fact, the cause. Cultural explanations are too easy—they allow us to dismiss the despair crisis as a problem that only affects morally and culturally flawed individuals. If we, instead, go deeper and explore how, precisely, we are failing systemically to integrate people into society, it is much more likely that we will find ways to intervene constructively. A more robust set of fundamental economic rights—to a good job with reasonable hours and paid family and medical leave; tertiary education relevant to one’s talents and inclinations; basic goods necessary to secure people against economic instability, like health care, housing, and energy—could help protect citizens against The Five A’s and, in this way, rescue them from despair. Insofar as cultural antagonisms are fueled by the feelings The Five A’s produce, new economic rights could help to soothe cultural tensions too.

What biomedicine gets wrong in responding to rising US mortality rates and Deaths of Despair

Peter Sterling

Francis Collins, on stepping down from 13 years as Director of the National Institutes of Health (NIH), published an essay titled “Precision Medicine in 2030—Seven Ways to Transform Healthcare.” With co-author Joshua Denny, he states: “Precision medicine promises improved health by accounting for individual variability in genes, environment, and lifestyle. Precision medicine will continue to transform health care in the coming decade as it expands in key areas: huge cohorts, artificial intelligence (AI), routine clinical genomics, phenomics and environment” (Denny and Collins 2021, 1415). The authors conclude: “The technologies undergirding precision medicine are already transforming care. Transformative molecular treatments have been developed for rare diseases … computation algorithms and high-resolution data will dramatically increase … to deeply measure our populations” (Denny and Collins 2021, 1419; edited for brevity).

Director Collins (and co-author Joshua Denny) could not have missed the Deaths of Despair mortality crisis, especially since the US National Academy of Sciences had just published its report High and Rising Mortality Rates Among Working-Age Adults (2021). Did Collins and Denny deliberately look away? How are we to understand Collins’s insistent focus on rare diseases, more drugs, and deeper measurements that skate over the surface of our rising medical crisis? And how are we to understand the National Academy’s failure to ask in its report how Western Europe avoids our problem? Denny and Collins’s essay and the National Academy’s report reflect the mindset and practice of the entire biomedical establishment in the United States, which defines every disturbance to human health as a medical disorder with a molecular cause to be treated at the molecular level. This approach to our crisis is hopelessly flawed.

Most of our deepest physical and mental disturbances are not merely biological disorders. All our physiological and mental systems evolved to function over a particular range of demands. When life circumstances drive them to the extremes of their evolved specifications, all systems adapt. However, when extreme circumstances prove chronic, all systems are driven chronically at the limits of their evolved specifications––that is, they are chronically abused––and then damage accumulates (Sterling 2020). Consider why our immense national investment in health care, as represented by former NIH Director Collins, fails to stem this rising mortality and how our biomedical community—with some provocation from the health humanities and social sciences—might respond. Consider the following examples at the core of our current Deaths of Despair crisis.

Hypertension

Our cardiovascular system evolved to operate with a mean arterial pressure of around 100 mm Hg. For efficiency, pressures are lower by night and higher by day according to need. This pattern, preserved across 200 millennia, still serves our extant hunter-gatherers and horticulturalists whose lives involve physical effort, sharp wits, and social cooperation. Such peoples remain fit across their lifespan. Their arterial pressures do not rise with age, nor do they exhibit cardiovascular or metabolic disturbance (Pontzer et al. 2018). But when human lives require neither effort nor wit nor cooperation nor sharing, arterial pressure starts to rise in childhood and advances continually with age (Fig. 2; Sterling 2020).

Fig. 2
figure 2

US: blood pressures rise as children enter school. By graduation, 25 percent reach the hypertensive range (140 mm Hg systolic). Reprinted from Sterling (2020)

Full size image

Precision medicine defines hypertension as a disorder when systolic pressure reaches a threshold of 140 mm Hg. But this is arbitrary. The neural systems regulating blood pressure are not broken; rather, they are responding to experienced socio-psychological stressors that tell the brain to prepare for higher demands. To meet prolonged stress, the brain adapts the body more extensively: arterial muscle thickens; kidneys retain more salt and water; salt appetite rises; and pressure-reducing mechanisms desensitize (Sterling 2020). Precision medicine typically focuses on genetic predisposition, which can help explain individual vulnerability but not our nearly universal rise of pressure with age or the broad prevalence of hypertension.

So-called precision drugs can block various pathways for raising pressure, but the brain compensates by driving others harder (Sterling 2020). A second precision drug can block another pathway, but again the brain compensates. Ultimately, precision pharmacology can dominate mechanisms for raising pressure, but then the individual cannot increase cardiac output to walk uphill. Moreover, since each drug affects multiple systems, improving one system commonly worsens others. For example, a beta blocker for the heart raises glucose in the blood, exacerbating type-2 diabetes and requiring more drugs. We can be stabilized by polypharmacy, but true health is responsiveness, which is what precision medicine impairs (Sterling 2020).

Since established hypertension enhances all sorts of cardiovascular pathology, it certainly needs treatment. But the most obvious need, all but ignored by precision medicine, is to treat the source: reduce chronic stress. When the brain predicts lower metabolic demand, it encourages the whole organism to readapt. Here emerges a therapeutic principle: strive for measures that (unlike polypharmacy) reduce prolonged excess demand and enhance responsiveness.

Obesity

Our bodily systems for feeding and digestion evolved to provide just the right nutrients in just the right quantities to fuel our catabolic needs for muscular activity and our anabolic needs for bodily surveillance, repair, and maintenance. It all works because of neural circuits inherited from worms that drive us insistently to seek––food, water, warmth, sex, companionship, and so on. When, following some effort, we find something better than expected, the circuit delivers a pulse of dopamine that allows a pause to our seeking––but only briefly––because seeking must resume in order to serve the next need. Dopamine cannot be commanded but only obtained from effortful activities that deliver positive surprises (Sterling 2018).

Humans who live without supermarkets, such as today’s hunter-gatherers and horticulturalists, obtain their daily dopamine pulses from food, water, and comfort that reward their individual efforts and communal cooperation. Such peoples remain lean with age. But when we obtain food without effort, surprise, or cooperation, it delivers little dopamine; moreover, the isolation and the stresses of poverty and social disruption reduce our social sources of dopamine. It is readily attainable, however, by eating sweet, greasy food (Kenny 2013). Thus, obesity starts in childhood and grows more prevalent with age (Wisconsin Health Atlas, n.d.).

Obesity, like hypertension, grows fastest and steepest in the most highly stressed communities with the least education, highest unemployment, and lowest quality jobs—that is, those most at risk for Deaths of Despair. Precision medicine searches for gene variants associated with obesity and finds thousands. But, as for hypertension, when most members of a population express the condition (73 percent of US adults are obese or overweight), genetics can help explain individual vulnerability but not why most of the population chronically overeats. A key clue: US maps for obesity strikingly resemble maps for Deaths of Despair (Ward et al. 2019).

Since obesity contributes to myriad pathologies, it attracts precision medicine to seek druggable targets. Some drugs try to burn off more fat per level of physical effort. Other drugs shed nutrients through the digestive and renal systems, and still, others tweak the brain to reduce appetite. But obesity, like hypertension, is not a molecular or neural disorder, and there is nothing to “fix.” Therefore, precision therapeutics simply seek control. Extreme cases are targeted for deep brain stimulation, and now many are treated with neuropeptides, such as semaglutide, that induce the brain to reduce appetite (Wilding et al. 2021). This strategy was tried before with a precision cannabinoid antagonist (Sam, Salem, and Ghatei 2011) that reduced satisfaction from eating. People ate less––but they grew depressed and suicidal. Will semaglutide now, in reducing our appetite for food, also reduce our appetite to live? Novo Nordisk, which markets semaglutide, does not inquire. Of course, it does not. At $1,300/month/person (Blum 2022), the potential US market of 70 million obese adults would earn the company over $1 trillion annually––20 percent of our current expenditure for all health care.

Drugs and alcohol

According to Nora Volkow, Director of the National Institute on Drug Abuse (NIDA),

We now understand substance use disorders (SUDs) to be chronic but treatable brain disorders. Adverse social determinants enable biological vulnerabilities to SUDs to emerge. Research has led to the development of effective prevention and treatment interventions, providing hope for the more than 40 million people in the United States with SUDs. (Volkow 2022)

In plainer words, drug addiction is said to be an intrinsic brain disorder poised to emerge following an unnamed adverse social determinant. Following the Director’s claim of effective interventions, she acknowledges: “Drug overdoses in the United States have been increasing exponentially for at least 40 years” (Volkow 2022; italics added), citing the dismal observations shown in Fig. 3. But obviously, if effective interventions existed, we would not be suffering this long-term rise.

Fig. 3
figure 3

Source: Volcow (2022)

US drug overdose deaths have been rising exponentially.

Full size image

NIDA’s research goals follow precision medicine in seeking molecular causes. But as for hypertension and obesity, there is no evidence of disorder. There is simply another instance where our seeking circuits demand some dopamine. When it is unavailable from effortful, challenging work, we seek it from drugs that, like junk food, release dopamine in great surges to which the circuits soon adapt and require larger doses that further escalate consumption. This adaptation is no disorder or dysregulation but a standard feature of all neural circuits; in fact, it is a key principle of neural design (Sterling and Laughlin 2015).

Yet, although lacking an identified disorder, NIDA seeks technical control, and to achieve this, it proposes new formulations of existing medications to improve the treatment of opioid use disorder; novel medications to treat all substance use disorders; immunotherapies, including vaccines, monoclonal antibodies, and other biologics; neuromodulation techniques, such as transcranial magnetic stimulation, peripheral nerve stimulation, and deep brain stimulation (NIDA 2022). The likelihood of solving our escalating drug problem with these fantasied measures is infinitesimal.

Alcohol has warranted a separate agency: the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Like NIDA, the NIAAA identifies alcohol addiction as a medical disorder (alcohol use disorder) and proposes technical approaches plus more research. Again, genome-wide association studies identify hundreds of genes associated with alcoholism, which can help explain how it distributes but not its considerable prevalence. Once more, none of the precision medicine approaches heralded by Collins and others have worked because the problems lie elsewhere. No technical approach can overcome our societal failure to fulfill the core needs of our evolved life cycle.

Mental disturbance

Mental disturbance presents the same story. Symptom clusters are defined arbitrarily as “disorders” according to a checklist (American Psychiatric Association 2013). The key categories—major depression, schizophrenia, and bipolar disorder—are most prevalent in the poorest, most distressed communities (as for hypertension, obesity, and drug/alcohol addiction). Depression is strongly predicted by childhood trauma (Caspi et al. 2020; Lippard and Nemeroff 2020). Moreover, like hypertension and obesity, mental disturbance is highly prevalent: a study by Caspi et al. (2020), for example, found that 86 percent of an urban population in New Zealand have experienced a diagnosable mental disturbance by age 45.

Mental disturbances are not largely attributable to genetic vulnerabilities since (like hypertension, obesity, and addiction) they are associated with thousands of gene variants of mostly small effect. Moreover, variants associated with the major categories of mental disturbance overlap substantially, perhaps suggesting an overarching disturbance with varied manifestations. Consistent with this overlap, disturbed individuals may experience depressive, schizophrenic, and bipolar symptoms simultaneously or intermittently as separate episodes across decades (Caspi et al. 2020).

These major disturbances, despite persistent claims, have not been localized to any brain region or neural circuit (Sterling 2022). Nor have they been associated with any disordered molecule or neurochemical imbalance (Ang, Horowitz, and Moncrieff 2022). Thus, an individual’s mental disturbance cannot be diagnosed by neuroimaging, genetics, chemical or molecular tests, or any other biological measure that would justify the term disorder. The state of this field has been summarized by neurogeneticist Daniel Geschwind as follows: “What we call psychiatric diseases are just levels of impairment. … The threshold is not scientific but a clinical/practical threshold for when individuals are unable to function in the world. These syndromic diagnoses are just one end of a continuum of normal variability” (Geschwind 2017).

Nevertheless, precision medicine offers another plethora of drugs––all brilliant in the narrow sense of their molecular specificity: Valium and Xanax bind to the GABAA receptor, allosterically enhancing its synaptic actions; Prozac and Paxil block serotonin transporters, increasing serotonin in the synaptic cleft; ketamine binds to the NMDA receptor, enhancing its postsynaptic actions; Clozaril, Risperdal, and Zyprexa antagonize various subtypes of dopamine receptors; Adderall and Ritalin increase dopamine in the synaptic cleft; Oxycontin and Fentanyl bind to opioid receptors.

But the drugs fail in the broad sense. First, as for hypertension, obesity, and addiction, there is no scientific rationale for tweaking neural circuits that are not broken (Sterling 2022). Boosting serotonin for someone suffering from depression is nothing more than a wild guess; indeed, for most people, psychopharmacology is roughly as effective as placebo (Khan et al. 2012; Stone et al. 2022). Second, as for hypertension, drugs that drive circuits or block them reduce overall responsiveness, which reduces progress toward cognitive and emotional health. Third, neither drugs nor bogus electrical and magnetic manipulations address the sources of trauma and stress that generate most mental disturbances and despair. Fourth, as for hypertension, obesity, and addiction, brain receptors adapt to the drugs administered for mental disturbance, rendering consumers drug-dependent and thus uncomfortable or miserable if they withdraw (Horowitz and Taylor 2022).

Some principles for population health

We cannot return to our hunter-gatherer lifestyle (Kaplan and Gurven 2005; Kaplan and Robson 2002; Boyd and Richerson 2009; Pontzer, Wood, and Raichlen 2018; Sterling 2020). Nor should we abandon the knowledge, products, and skills achieved by biomedicine’s brilliant trajectory. Right now, however, we need some principles to guide us past the current Deaths of Despair crisis.

Start with Hippocrates’ injunction to “first, do no harm.” Precision medicine, while certainly doing good, also does considerable harm. Deaths attributable to medical error are estimated at 10 percent of all deaths, the third leading cause in the US (Makary and Daniel 2016). Moreover, beyond preventable errors, harm is done by full-bore polypharmacy that stabilizes unhealthy individuals but reduces their responsiveness, the true measure of health. Thus, a corollary to Hippocrates: shift the foundation of therapeutics from polypharmacy toward fundamentals. Consider four features of human design with implications for a healthy life cycle.

First, our species’ success depends on a large brain that matures gradually. Neonatal circuits just suffice to keep us breathing, sucking, and emitting sounds and aromas that reward persistent care. Nutritional and emotional dependence continues throughout childhood and adolescence (Sterling and Platt 2022). Were this 20-year debt assumed by just two adults, births would need to be spaced more widely, and our species would risk extinction through failure-to-replace (Kaplan and Robson 2002). So, for 200 millennia, our innate circuits fostered an obligatory, intense sociality (Boyd and Richerson 2009; Muthukrishna and Henrich 2016). But now, with diminishing assistance from grandparents and often not even a second parent, despair rises. We are constantly spurred toward socio-economic independence and resilience. But, as independence––isolation––so powerfully opposes our evolved nature, it proves unmanageable (Sterling and Platt 2022).

This evidence of our obligatory prolonged dependence suggests another principle for biomedicine: invest in prenatal care and every sort of postnatal care––physical and emotional––for families during early childhood and adolescence. Absent assistance from grandparents and neighbors, society must nurture families by providing parental leave, daycare, preschool, and family vacations. Relief from chronic stress by guaranteeing some income would help stabilize adult unions and reduce child abuse, which causes mental disturbances whose prevalence in an urban population reaches 50 percent by the age of 18 (Caspi et al. 2020). For example, a simple intervention like cash payments to families leads to better child mental health (Sears 2022).

Second, our species’ success depends on extreme variation between individual brains (Sterling 2020). Every brain either omits certain cortical circuits or shrinks them, leaving deficits but opening territory for other circuits to expand. Thus, evolution endowed every small community with individuals that possess different innate talents, who then developed them through play (Gray 2013). This diversity suggests another principle for health: structure childhood education around helping children discover and practice their innate talents.

Such a return to our evolved method of education would greatly reduce the prevalence of what is diagnosed as ADHD (attention deficit hyperactive disorder) and its extensive precision treatment with addictive stimulants. Naturally, there should be instruction in fundamental skills (reading, writing, and arithmetic) while recognizing that our innately diverse cortical circuitry makes acquiring a particular skill harder for some, who therefore need more assistance (Gray 2013). We also need real physical education to make physical activity a lifelong pleasure and habit––essential to healthy aging––and thus change from our current state where most physical activity is vicarious (e.g., watching professional sports).

Third, our species evolved play and practice to prepare adolescents for adult levels of mental and physical effort. When they were finally admitted (around the age of 20) to the community of adult hunter-gatherers/horticulturalists, there were trades to learn and skills to expand over decades. Thus, for 200,000 years, since our species’ emergence, careers had an arc with learning across the lifespan. But 200 years ago (0.1 percent of our species’ existence), the steam engine spurred rapid industrialization, which confined great masses of people in mines and mills, where their evolved needs could not be expressed. Although we evolved to explore the planet, multitudes now punch a ticket or scan a bar code. This mismatch between our abilities, on the one hand, and our opportunities to exercise them, on the other, is a wellspring of despair (Sterling 2020). Thus, another principle for health: restructure our economy to ensure that the innate talents developed during childhood and adolescence can be exercised across the adult years.

Fourth, our brain devotes considerable space and energy to cortical circuits that have no obvious economic value but foster cognitive and emotional health. These are circuits for various forms of sacred practice, including graphic art, music, dance, storytelling, and visions fostered by meditation, trance, and prayer––sometimes enhanced by social use of stimulants and psychedelics. Such activities, once practiced within a small community, are now widely experienced alone via small screens and earbuds. Thus, another principle: invest in diverse sacred practices that deliver us from the vicarious to the participatory.

To follow such broad principles for treating despair, biomedicine must identify in detail the conditions and social relationships that cause the anomie and alienation that lead to suicide in all its forms. These conditions emerged as part of the capitalist system of production and were studied deeply in the nineteenth century by observers such as Marx and Durkheim. The essay by Benjamin Studebaker earlier in this collection treats this topic with clarity and suggests, at a finer level, what needs to be fixed.

Who will pay?

Principles and new programs are fine, but always comes the question: Who will pay? The math is simple. The US now spends 20 percent of its GDP (gross domestic product) on health care. Western European democracies spend half that––precisely because they support all the above-mentioned social measures. Reallocating half of our current investment in precision medicine would free $2.5 trillion––which would go a long way toward implementing these principles and reversing the curve of our rising mortality. Allocation of funds could be guided by European experience with adjustments, of course, for cultural differences.

What to do about despair: Imagining potential roles for the health humanities

Megan S. Wright and Cindy L. Cain

The US is currently mired in a life expectancy crisis that reaches beyond the COVID-19 pandemic and implicates the morbidity and mortality caused by substance misuse or abuse and suicidality (Brignone et al. 2020; Case and Deaton 2017; Parmet and Huer 2018). While there is debate about what has precipitated an increase in diseases and subsequent Deaths of Despair, prominent scholars Case and Deaton (2015, 2017, 2020) hypothesize that this increase is the result of the decline of the white working class over the past several decades and, more specifically, of societal changes such as fewer job opportunities for individuals without a college degree and a decline in their marriage rates, religious participation, and other forms of social cohesion. Fewer opportunities and lower levels of social cohesion for this population lead to lower individual and family income and increased isolation. Low income and social isolation lead to a decline in social status accompanied by feelings of hopelessness and despair, which are theorized to increase risky, pain-numbing behaviors that may lead to preventable disease, injuries, and death. They call their explanation of DoD one of “cumulative disadvantage” and express pessimism that policy can quickly respond to this problem (Case and Deaton 2017; Parmet and Huer 2018).

Economists and health services researchers have documented the DoD phenomenon, and there have been responses both at the level of law and policy and at the level of the clinical encounter. While such descriptions and responses are necessary, we need to ensure that other scholarly perspectives are included—in particular, the disciplines that make up the health humanities—and to bring their respective strengths in responding to this social crisis.

In the remainder of this brief essay, we offer a few thoughts about how the humanities disciplines can help us understand and respond to DoD. Specifically, we argue that humanities scholars have a role in focusing on the lived reality of despair, ensuring that interventions target despair rather than solely the downstream diseases and deaths caused by it, complicating narratives about what populations suffer from despair and why, and imagining a better future. We write from our viewpoints as medical sociologists, bioethicists, and law and policy scholars, and we realize that ours is only a partial perspective and that others in the health humanities will have additional insights to offer.

Understanding despair and humanizing those affected

Although the concept of DoD is an improvement upon earlier understandings of deaths caused by substance misuse or suicide in that the term draws attention to the social conditions that may give rise to feelings of despair, there is inadequate awareness of the experience of despair and its causes. As others have noted, “The concept of despair remains largely understudied, with manifestations in cognitive, emotional, behavioural and biological domains as well as in social and political-economic contexts” (Brignone et al. 2020, 8). Scholars in the humanities can focus on understanding the despair that is leading to preventable diseases and death, using best practices of their disciplines, be it historical analysis, textual or narrative analysis, arts-based or musical approaches, qualitative methods, quantitative methods, or other perspectives.

Economists and others using quantitative methods have done a remarkable job of documenting DoD, and much of the current literature on the subject is dominated by tables and graphs. But the numbers can be overwhelming. In fact, psychologists have documented “compassion fade,” defined as the phenomenon where, as the number of people suffering increases, people’s compassion is reduced, and they eventually are unable to feel for others at all (Butts et al. 2019). We witnessed this happen as data on COVID-19 deaths were widely publicized, and it is reasonable to presume the same thing is happening with DoD.

Scholars in the health humanities can go even further to humanize the people who become numbers in the tables and graphs. Telling the stories of people affected, using arts and expressive mediums to communicate the experience of despair, and generating social and political support for policies that would reduce despair are all worthwhile goals for the work of the health humanities. For those in empirical areas, qualitative research is ideal for creating this more complete story (Brignone et al. 2020). Quantitative approaches and mixed-methods designs could also be used in ways that better humanize and give a face to the numbers.

Targeting interventions appropriately

Although preventing despair is a logical place to focus resources, many of the medical, public health, and policy responses to DoD in the US have focused on the stage after the onset of despair, when social problems manifest in medical settings. For example, harm reduction strategies such as prescribing methadone for opioid use disorder are only appropriate once someone already has the disorder, and such substance abuse treatment does nothing to address the cause of the disorder, including tending to suffering that leads to substance use. As another example, cutting-edge drug trials are taking place right now to find a safe and effective pharmaceutical intervention to treat addiction to methamphetamine, thereby reducing over 20,000 deaths annually (Facher 2022). But even if this drug is ultimately approved by the US Food and Drug Administration, the compound may save lives but will not address the underlying causes of addiction. Outside the substance use context, some have suggested that physicians should ask their patients whether they have access to firearms, discuss firearm safety, and screen for suicidality and violence to try to reduce injuries and deaths from firearms (Ryan 2019). But such screening does little to address the suffering that may prompt an individual to use a firearm to harm themselves or others. Furthermore, laws and policies designed to reduce access to firearms or substances do not tend to suffering, only mitigating the consequences of what people do in response to their suffering.

In brief, when medicine responds to DoD, it is generally late in the crisis, and clinical interventions address symptoms rather than causes. Indeed, as other scholars have argued, “[W]hile a better understanding of the clinical manifestation of diseases of despair may inform efforts at targeted intervention and mitigation, it must be acknowledged that the ultimate public health goal must be addressing structural root causes of despair” (Brignone et al. 2020, 5 and 8). Social determinants of health approaches are part of this mission to address root causes, but when the medical system intervenes in the late stages of despair, there are challenges to identifying patient and community needs, developing solutions, and garnering support and resources for implementation.

Additionally, there are reasons to be cautious about focusing on the clinic as a site for solutions to DoD, in part because solutions in this context concentrate more power in the hands of clinicians relative to patients and society as a whole (Wright 2022). Further, if the causes of such deaths and comorbidities are indeed due to structural conditions such as lack of socioeconomic stability or social cohesion (as is argued in the essays above), it is somewhat peculiar and obviously insufficient to ask physicians to take the lead on addressing the issue, given that they are medical experts and not public policy experts or social workers. Focusing on medicine and doctors to tend to DoD is, in effect, medicalizing social problems; moreover, addressing structural problems with individual-level interventions is a mismatch. Instead, perhaps we can use our fuller knowledge of how social factors affect morbidity and mortality to design stronger social structures and more supportive communities.

Indeed, we need to take care when educating future physicians that they understand the social determinants of health and know the limits of their expertise (i.e., teach them humility) while also training them to do what they can to prevent disease and death due to social factors. The health humanities can serve a vital role in this training, as the Association of American Medical Colleges recognizes, noting that the humanities are necessary for the development of physician empathy and communication skills.

Complicating existing narratives

Better solutions require a more complete picture of populations affected by despair. While Case and Deaton (2015) examined mortality trends in the post-industrial white working class to develop their narrative about the causes of DoD, it is important also to acknowledge (as Case and Deaton do in their follow-up study [2017] and book [2020]) that a rise in excess mortality—especially related to social causes like substance use, injury, and suicidality—is also observable in other groups. Moreover, large-scale social inequality is exacerbating life expectancy gaps between advantaged and disadvantaged groups (Gutin and Hummer 2021). For instance, suicide rates for Black youth (10–19 years old) have risen by 60 percent in the last 20 years, a bigger increase than any other group (American Academy of Child & Adolescent Psychiatry 2022). And as others have noted, while the increase in premature deaths of working-class whites has generated significant media attention, these issues—particularly substance abuse and suicide—have long been leading causes of death for American Indian and Alaska Native populations (Komro 2018); however, their exclusion from existing quantitative analyses hides this fact, a phenomenon referred to as “Indigenous data genocide” (Friedman, Hansen, and Gone 2023). Even these trends are conditioned by gender, age, sexual orientation, marital status, disabilities, citizenship, and other social statuses. Indeed, recent scholarship has shown that drug overdose mortality is high and increasing for Black women, in part due to “institutional racism and sexism” (Harris and Mandell 2022, E2). The health humanities have a role in bringing to light the diversity of experiences of despair and how they shape one’s life chances. Humanists must craft another narrative about this problem rather than only emphasizing the decline of the white working class.

Imagining a better future

Another role for those in the health humanities is to imagine interventions for and solutions to DoD beyond what currently exists in the scholarly and policy literature. This literature focuses largely on clinical settings for intervention because the outcome of despair so often manifests as a medical problem to be treated and because clinical interventions are perhaps the only feasible solution in our dysfunctional political environment. But one role of the humanities is to think beyond what is currently possible and imagine a variety of better, more creative interventions—that is, the health humanities can be somewhat utopian rather than purely pragmatic and push the conversation toward other possibilities.

Indeed, if we humanize individuals who are suffering due to hopelessness in the face of structural problems by using their stories and narratives, we may be able to obtain public support that can later be converted into political support for policies that currently seem impossible in a highly polarized and broken political system. We have seen this phenomenon in the context of long-stalled health care reform where, over the past decade, states have expanded Medicaid over the objection of their legislatures when voters directly decide on the issue, in part due to campaigns highlighting residents’ lived experiences with health care. The health humanities can imagine solutions to despair outside of the health care system and then work to build political will to implement these solutions locally and more broadly, improving conditions for all affected by despair.