Regardless of the metric chosen, any map of the burden of disease exposes disparities within and among populations. Two aspects of the burden of disease have remained particularly vexing: changes over time in the prevailing diseases and the persistence of health inequalities.

By examining the many new diseases that have appeared over the past two centuries, historians have categorized the ways in which diseases emerge. New causes (e.g., severe acute respiratory syndrome, motor vehicle accidents, radiation poisoning), new behaviors (cigarette smoking, intravenous drug use), and even the consequences of new therapies (insulin transforming the course and manifestations of diabetes) can produce new diseases. Changing environmental and social conditions can increase the prevalence of once-obscure ailments (myocardial infarction, lung cancer, kuru, and “mad cow” disease). New diagnostic technologies and therapeutic capacity can unmask previously unrecognized conditions (hypertension). New diagnostic criteria can expand a disease's boundaries (hypercholesterolemia, depression). Changing social mores can redefine what is or is not a disease (homosexuality, alcoholism, masturbation). New diseases can emerge as the result of conscious advocacy by interested parties (chronic fatigue syndrome, sick building syndrome). HIV–AIDS alone demonstrates many of these modes of emergence. The emergence, recognition, and impact of disease are never just a bioscientific process; the advent of a new disease always involves social, economic, and political processes that shape its epidemiology and influence our understanding and response.

The interaction between the biologic and the social is equally apparent in the decline of a disease. Cannonball injuries, a frequent cause of concern in 1812, disappeared from the Journal, only to be replaced by a new and more terrible litany of war-related injuries. Neurasthenia, a widespread phenomenon of depleted nervous energy in the late 19th century, has disappeared, but traces of it have remained recognizable in other diagnoses throughout the past century. In some cases, a disease's decline clearly resulted from medical action. Immunizations eradicated smallpox and may someday eradicate polio. Genetic screening has led to dramatic reductions in Tay–Sachs disease, thalassemia, and familial dysautonomia (2009). But often the potential for eradication has been incompletely realized — witness the continued prevalence of AIDS and tuberculosis in low-income countries and of atherosclerotic heart disease globally.

Even as prevailing diseases have changed, health disparities have endured. Inequalities in health status have always existed, regardless of how health has been measured or populations defined. When Europeans arrived in the Americas, they witnessed stark disparities in the fates of European, American, and African populations. During the ravages of 19th-century industrialization, physicians grew familiar with health disparities between rich and poor. Health inequalities remain ubiquitous, not just among races and ethnic groups but also according to geography, sex, educational level, occupation, income, and other gradients of wealth and power.5

The persistence of health inequalities challenges our scientific knowledge and political will. Can we explain them and alleviate them? Genetic variations don't explain why mortality rates double as you cross Boston Harbor from Back Bay to Charlestown or walk up Fifth Avenue from midtown Manhattan into Harlem. Nor do they explain why Asian-American women in Bergen County, New Jersey, live 50% longer than Native American men in South Dakota.6 Although we know something about the relationships among poverty, stress, allostatic load, and the hypothalamic–pituitary–adrenal axis, doctors and epidemiologists need more precise models that sketch in the steps between social exposure, disease, and death.

Accounting for the history of disease also requires us to examine why some disparities in disease are seen as proof of a natural order while others are considered evidence of injustice. The 4.3-year life-expectancy gap between blacks and whites in the United States provokes outrage, but the 4.9-year gap between men and women does not. It is tempting to assume that differences between the sexes are natural and those between races are not. But a 19th-century Journal reader might be skeptical of this explanation: men then lived at least as long as women. The survival advantage of women that appeared in the 20th century owed as much to changes in childbearing, improvements in obstetrical practice, and a new epidemic of heart disease disproportionally affecting men as to differences between the X and Y chromosomes. Disparities in health and disease are outcomes that are contingent on the ways society structures the lives and risks of individuals.

Recognition of the contingency of health inequalities should make them a target for intervention, yet the opposite has frequently happened: the ill health of impoverished or marginalized groups has been used against them — as evidence of their inferiority or as an argument that they're unworthy of assistance. In the late 19th and early 20th centuries such sentiments produced government policies with tragic outcomes for blacks and Native Americans. They may underlie current policies that would limit health care access for mentally ill, impoverished, and immigrant populations.