By Atul Gawande, New Yorker, Costa Ricans Live Longer Than Us. What’s the Secret?, August 23, 2021
In the United States and elsewhere, public health and medical care are largely separate enterprises. Costa Rica shows the benefits of integrating the two—it spends less than we do on health care and gets better results.Photographs by Fred Ramos for The New Yorker
The cemetery in Atenas, Costa Rica, a small town in the mountains that line the country’s lush Central Valley, contains hundreds of flat white crypt markers laid out in neat rows like mah-jongg tiles, extending in every direction. On a clear afternoon in April, Álvaro Salas Chaves, who was born in Atenas in 1950, guided me through the graves.
“As a child, I witnessed every day two, three, four funerals for kids,” he said. “The cemetery was divided into two. One side for adults, and the other side for children, because the number of deaths was so high.”
Salas grew up in a small, red-roofed farmhouse just down the road. “I was a peasant boy,” he said. He slept on a straw mattress, with a woodstove in the kitchen, and no plumbing. Still, his family was among the better-off in Atenas, then a community of nine thousand people. His parents had a patch of land where they grew coffee, plantains, mangoes, and oranges, and they had three milk cows. His father also had a store on the main road through town, where he sold various staples and local produce. Situated halfway between the capital, San José, and the Pacific port city of Puntarenas, Atenas was a stop for oxcarts travelling to the coast, and the store did good business.
On the cemetery road, however, there was another kind of traffic. When someone died, a long procession of family members and neighbors trailed the coffin, passing in front of Salas’s home. The images of the mourners are still with him.
“At that time, Costa Rica was the most sad country, because the infant-mortality rate was very high,” he said. In 1950, around ten per cent of children died before their first birthday, most often from diarrheal illnesses, respiratory infections, and birth complications. Many youths and young adults died as well. The country’s average life expectancy was fifty-five years, thirteen years shorter than that in the United States at the time.
Life expectancy tends to track national income closely. Costa Rica has emerged as an exception. Searching a newer section of the cemetery that afternoon, I found only one grave for a child. Across all age cohorts, the country’s increase in health has far outpaced its increase in wealth. Although Costa Rica’s per-capita income is a sixth that of the United States—and its per-capita health-care costs are a fraction of ours—life expectancy there is approaching eighty-one years. In the United States, life expectancy peaked at just under seventy-nine years, in 2014, and has declined since.
People who have studied Costa Rica, including colleagues of mine at the research and innovation center Ariadne Labs, have identified what seems to be a key factor in its success: the country has made public health—measures to improve the health of the population as a whole—central to the delivery of medical care. Even in countries with robust universal health care, public health is usually an add-on; the vast majority of spending goes to treat the ailments of individuals. In Costa Rica, though, public health has been a priority for decades.
The covid-19 pandemic has revealed the impoverished state of public health even in affluent countries—and the cost of our neglect. Costa Rica shows what an alternative looks like. I travelled with Álvaro Salas to his home town because he had witnessed the results of his country’s expanding commitment to public health, and also because he had helped build the systems that delivered on that commitment. He understood what the country has achieved and how it was done.
When Salas was growing up, Atenas was a village of farmers and laborers. Cars were rare, and so were telephones. A radio was a luxury. In the country at large, barely half the population had running water or proper sanitation facilities, which led to high rates of polio, parasites, and diarrheal illness. Many children did not have enough to eat, and, between malnutrition and recurrent illnesses, their growth was often stunted. Like other societies where many die young, people had big families—seven or eight children was the average. Many children left school early, and only a quarter of girls completed primary education. Salas said that most children in Atenas started elementary school, but each year more and more were pulled out to do farmwork.
Important progress was achieved in the nineteen-fifties and sixties in Costa Rica, with the kind of basic public-health efforts made in many developing countries. Salas was in kindergarten, he thinks, when his family was able to pipe running water to their home from the nearby city center. A national latrine campaign provided people with outhouses made of cement. National power generation brought electrical wiring. “The most happy person was my mother!” he said.
Vaccination campaigns against polio, diphtheria, and rubella reached Salas and his classmates when he was in elementary school, as did a child-nutrition program that the government rolled out across the country, with aid from the Kennedy Administration. “We had this lunch—hot food,” he recalled. “I still have the flavor in my mouth. It was very nice to have a plate of soup with rice.” His family, with its cows and its store, was never nutritionally deprived—Salas grew to six feet—but his friends were often hungry. And so school attendance jumped. “The mothers and the families saw that it was a good idea now to send the kids to school, because they were fed,” he said.
Along the way, the Ministry of Health provided an official in every community with resources and staff devoted to preventing infectious-disease outbreaks, malnutrition, toxic hazards, sanitary problems, and the like. These local public-health units, geared toward community-wide concerns, worked in parallel with a health-care system built to address individual needs. Still, both remained rudimentary in Atenas. The nearest hospital was sixteen miles away, in the city of Alajuela, and understaffed. “At that time, it was far, because the road was impossible,” Salas said.
So when did Costa Rica’s results diverge from others’? That started in the early nineteen-seventies: the country adopted a national health plan, which broadened the health-care coverage provided by its social-security system, and a rural health program, which brought the kind of medical services that the cities had to the rest of the country. Atenas finally got a primary-care clinic. “With two or three doctors,” Salas recalled. “With five nurses. With social workers. For everything.” In 1973, the social-security administration was charged with upgrading the hospital system, including in Alajuela and other rural regions. In this early period, the country spent more of its G.D.P. on the health of its people than did other countries of similar income levels—and, indeed, more than some richer ones. But what set Costa Rica apart wasn’t simply the amount it spent on health care. It was how the money was spent: targeting the most readily preventable kinds of death and disability.
That may sound like common sense. But medical systems seldom focus on any overarching outcome for the communities they serve. We doctors are reactive. We wait to see who arrives at our office and try to help out with their “chief complaint.” We move on to the next person’s chief complaint: What seems to be the problem? We don’t ask what our town’s most important health needs are, let alone make a concerted effort to tackle them. If we were oriented toward public health, we would have been in touch with all our patients, if not everyone in the communities we serve, to schedule appointments for vaccination against the coronavirus, the No. 3 killer in the past year. We would have coördinated with public-health officials to prevent cardiovascular disease, the No. 1 killer, by jointly taking aim at high blood pressure and cholesterol, smoking, and dietary salt intake. We would have made a priority of preventing disease, rather than just treating it. But we haven’t.
In the nineteen-seventies, Costa Rica identified maternal and child mortality as its biggest source of lost years of life. The public-health units directed pregnant women to prenatal care and delivery in hospitals, where officials made sure that personnel were prepared to prevent and manage the most frequent dangers, such as maternal hemorrhage, newborn respiratory failure, and sepsis. Nutrition programs helped reduce food shortages and underweight births; sanitation and vaccination campaigns reduced infectious diseases, from cholera to diphtheria; and a network of primary-care clinics delivered better treatment for children who did fall sick. Clinics also provided better access to contraception; by 1990, the average family size had dropped to just over three children.
The strategy demonstrated rapid and dramatic results. In 1970, seven per cent of children died before their first birthday. By 1980, only two per cent did. In the course of the decade, maternal deaths fell by eighty per cent. The nation’s over-all life expectancy became the longest in Latin America, and kept growing. By 1985, Costa Rica’s life expectancy matched that of the United States. Demographers and economists took notice. The country was the best performer among a handful of countries that seemed to defy the rule that health requires wealth.
Some people were skeptical. Costa Rica had endured numerous economic crises before 1970; perhaps the subsequent decade of economic stability had made the difference. Or maybe it was the country’s large investment in education, which had lifted the proportion of girls who completed primary education from a quarter in 1960 to two-thirds in 1980. A careful statistical analysis indicated that such factors did contribute to child survival—but that eighty per cent of the gains were tied to improvements in health services. The municipalities with the best public-health coverage had the largest declines in infant mortality.
A big question remained, though: Could Costa Rica sustain its progress? Public-health strategies might be able to address mortality in childhood and young adulthood, but many people believe that adding years from middle age onward is a wholly different endeavor. Countries at this stage tend to switch approaches, deëmphasizing public health and primary care and giving priority to hospitals and advanced specialties.
Costa Rica did not change course, however. It kept going even farther down the one it was on. And that’s where Álvaro Salas comes in.
Salas was an exuberant and ambitious child, and in high school he decided to become a doctor, inspired by two physician friends of his father’s who told stories about treating the wounded during the Second World War. He was one of only a few from his high-school class to go to college, and one of the first in his family to do so. When he enrolled at the University of Costa Rica, then the country’s sole public university, he imagined he’d return to Atenas to practice one day. As an undergraduate, though, he met people from across the country and came to understand that the gaps he’d experienced were present everywhere.
“I became very active in politics,” he recalled. “But I hated the people who speak and speak and do nothing. So I decided to organize groups of premedical students to visit poor communities in the country and to bring students from the third year or fourth year in the school of medicine to treat them.” Salas turned out to have a Pied Piper charm and a talent for getting things done, even as a freshman. The medical school’s dean, he learned, had close connections at the Ministry of Health. He met with the dean, and came away with both medical-faculty support and ministry supplies for his venture.
In his travels, Salas discovered that many of Costa Rica’s villages were even poorer than Atenas. “They had tuberculosis, they had leprosy, they had everything,” he said. He continued his volunteer work through college and medical school. And, as the country adopted its national health plan and spent more on public health, he could see not only what a difference such actions made but how much remained to be done. “My goals got bigger,” he said.
In 1977, after his medical internship, he went to work in the Nicoya Peninsula, on a government-funded year of social service. Now a tourist destination, known for its beaches and for having one of the largest populations of centenarians in the world, the peninsula was then a remote and impoverished region, where medical care was sparse and lives were precarious.
Salas was put in charge of setting up a new mobile public-health unit, one of many deployed in the government’s rural health program. When you work at a hospital, patients come to you. In a public-health unit, you have to go to them. Salas and his team made visits to villages along the sea. In addition to treating patients, they conducted household surveys, and pieced together diagnoses of whole communities. He found high rates of severe anemia among women, water contaminated with parasites, and outbreaks of respiratory infections. Owing to the new reforms, Salas could now do something about what he observed. Members of his team distributed iron tablets and vitamins and basic medicines such as antiparasitics and antibiotics. They helped organize sites for clean drinking water. They fought malaria and outbreaks of other infectious diseases. And, in the data they collected and the people they encountered, Salas could see the benefits.
At year’s end, he was hired at a hospital in Puntarenas. But, after his experience in Nicoya, he did not think the way most clinicians do. “At that time in Costa Rica, it was very common to see people with blankets outside the hospital, pillows, waiting for a bed,” he told me. Elsewhere, people were living in squatter settlements and slums without roads, electricity, or sanitation. “For me, it was very clear that hospitals have a role, but we have to work at the community level first.” The government was building a housing development for around a thousand residents in a barrio called El Roble. Salas proposed to the hospital director that one of the new houses be turned into a neighborhood clinic—to save people from having to go to the hospital.
Salas’s voluble exuberance was again persuasive. The director gave him a staff of two, and the housing authority gave him a house. The clinic was small, with a waiting room in front and an examining room in back. Just as in Nicoya, he and his team went door to door, creating a record for every family.
“Didn’t people find that strange?” I asked.
“I had a very nice uniform,” Salas said, laughing. “Green surgery scrubs.”
He was a bear of a man, with a walrus mustache, a desk-drawer chin, and a head of dark, wavy hair; his ebullience was tempered with an air of kindness. No one in El Roble turned him away. “We knew everything,” he said. “Who is pregnant, who has a child, who has a malnutrition problem.”
Salas became a neighborhood doctor and a public-health officer rolled into one. In addition to drawing blood for basic lab tests, he and his team collected stool samples to look for parasites. Because they also tested for blood in the stool, Salas detected one patient’s colon cancer early enough that it could be treated before it spread.
A few months after opening the clinic, Salas asked the hospital to let him open another. The director again said yes. “Because the results were very good,” Salas said. “They had less people coming to the hospital—less lines, less waiting lists.” He set up a physician and more nurses in another Puntarenas barrio, a poorer one. “Again, the results were very good.”
Then, one day, he got a call from a regional director of the country’s health-care agency, the C.C.S.S., known simply as “the Caja” (“the Fund”).
“He was so angry, so angry,” Salas said. Salas had been commandeering C.C.S.S. doctors, nurses, and funds without going through proper channels. His engine of charm hit a barrier. “Who approved this project?” he recalls the director demanding.
“I am responsible,” Salas replied.
“No, you are not responsible,” the director told him. “You are irresponsible. Irresponsible in the worst sense possible, because you are making crazy things without any kind of studies.”
The director delivered Salas’s punishment. Salas, at the age of twenty-eight, was to be the new head of the city’s central clinic. He was being kicked upstairs. “I had to move from El Roble to the center,” he said. He accepted it, but he didn’t give up: “I found that I had now my own resources, my own nurses, my own doctors. So I decided to continue with the project, but in silence.”
The next election brought a change of government, and the new head of the C.C.S.S. was someone Salas knew from medical school. “So I went to San José saying, ‘Doctor, I have this project,’ ” he recalled. He brought pictures of the El Roble clinic, clicking through slides on a Kodak carrousel. The executive was impressed. “He said to me, ‘You have to show this to the President.’ ”
They took the carrousel of slides to the President’s office that day. “The thing is that he used to live in Puntarenas,” Salas said. “So the President loved Puntarenas—loved.” He offered to provide whatever Salas needed. “I had a year in paradise with resources. That was amazing.”
It was the late nineteen-seventies, however, and the oil crisis brought hyperinflation. Budgets were cut; jobs were lost. The El Roble clinic abruptly closed. Around the same time, across the northern border of Costa Rica, the Sandinistas had taken power in Nicaragua, in a bloody civil war. Hundreds of thousands of people were homeless. Many doctors had fled. Salas ventured north and found work in Nicaragua’s new government, helping to rebuild the health-care system along its impoverished Mosquito Coast, where no one else wanted to go.
After three years, he returned to Costa Rica. Salas was now married to a young woman from Atenas and about to become a father. He took a job as a general practitioner in the city of San Carlos, and then found one in San Ramón, closer to his home town. There, a physician named Juan Guillermo Ortiz Guier had built a program called Hospital Without Walls, which had opened health posts not dissimilar to Salas’s El Roble clinic—but in dozens of neighborhoods. “That inspired me,” Salas said. He began talking to Ortiz and working with friends on a proposal to bring the essential concepts to Costa Rica’s entire health system.
During the next eight years, Salas was promoted to run a major hospital in the capital and earned a master’s degree at Harvard’s Kennedy School of Government, but in 1990 he finally got the chance to put his ideas into action. He was appointed to lead policy development for the C.C.S.S., the Caja, working with a staff of fifty. Together, they delivered a plan for a universal system of care that would braid together public health and individual health.
The plan had three principal elements. First, it would merge the public-health services of the Ministry of Health with the Caja’s system of hospitals and clinics—two functions that governments, including ours, typically keep separate—and so allow public-health officials to set objectives for the health-care system as a whole. Second, the Caja would integrate a slew of disparate records, combining data about household conditions and needs with the medical-record system, and would use the information to guide national priorities, set targets, and track progress. Third, every Costa Rican would be assigned to a local primary-health-care team, called an ebais (“eh-by-ees”), for Equipo Básico de Atención Integral en Salud, which would include a physician, a nurse, and a trained community-health worker known as an atap (Asistente Técnico en Atención Primaria). Each team would cover about four or five thousand people. The ataps would visit every household in their assigned population at least once a year, in order to assess health needs and to close the highest-priority gaps—the way Salas’s team in El Roble had done.
The plan was at once breathtaking in scope and beautifully simple, and the President embraced it immediately. Funding it took longer. Although Costa Rica had a long track record of stability and economic growth, international financial institutions resisted Salas’s proposal. Providing real primary care, with a doctor on each team, would be too expensive, the World Bank said. “We could have a small package of basic services, no more than that,” Salas told me, recalling the negotiations. “But we already had that!” Hospitals were at capacity, and he insisted that the solution wasn’t just to build more of them.
In 1994, the loans finally came through, and the plan was submitted to the legislative assembly, where it passed unanimously. A new government was elected, under the center-left President José María Figueres, but the plan had its full support. In fact, Figueres appointed Salas to be the head of the C.C.S.S.
Getting the bill passed without opposition would seem no small feat: Salas had made his pitch to a center-right government, then retained the backing of a center-left one. But, if such unanimity is hard to imagine in the United States, President Figueres told me that it wasn’t surprising in Costa Rica. “This is something which, in our culture, is politically easy to sell,” he said. It would put a doctor, a nurse, and a community-health worker in every neighborhood. Who could object to that?
Still, by the time Salas got the financing, there were just three years until the next election. So he rolled out the plan at breakneck speed. By 1998, when the government changed again and he left his post, the country had established enough ebais teams to reach about half the population, beginning with underserved rural areas. At that point, he wasn’t worried that the program would be dismantled. “It was in the news,” he said. “On the TV. We started in the north and then in the south. It became like a fashion to have an ebais. Everybody wanted one. The pressure to have an ebais became impossible to control.” By 2006, nearly the entire population had been enrolled with an ebais. Universal insurance coverage—to pay for hospitalizations and specialized care—would take longer. But universal primary care, delivered by more than a thousand local teams and with an emphasis on prevention and public health, was now a reality.
Today, Álvaro Salas lives with his wife in San José and continues to advise the government, political figures, and, through media appearances, the public. He is seventy years old, with a fringe of short gray hair and a trim salt-and-pepper mustache. His attire leans toward track shoes with khakis and an Apple Watch. When I asked him to accompany me as I visited Atenas this spring, an outbreak of covid-19 was rippling across the country. The pandemic had been under control for a year in Costa Rica, but more contagious variants had arrived and the I.C.U.s were full.
On a sunlit, tropical morning, we made our way into town, past the palm-tree-filled park and the Spanish-style parish church, to the Atenas central clinic, a jumble of airy, low-slung, cream-colored buildings. Leonardo Herrera, an atap in the area, was preparing to head out for the morning’s home visits. In an open garage beside the clinic, several rows of elderly residents had just received covid vaccines and were waiting in chairs for their observation period to end. For the now roughly thirty thousand people who live in Atenas and the surrounding area, there are seven fully staffed and equipped ebais teams.
ataps, a category of clinician we don’t have, combine the skills of a medical worker and a public-health aide. They are professionally trained, salaried, and proud. Herrera, whose dark eyes showed a desire to get moving, wore a long-sleeved white shirt, blue pants, and black shoes, with credentials dangling from a lanyard around his neck. He carried with him a backpack of medical supplies, a tablet computer, and a cooler of covid vaccines.
Each atap is responsible for visiting all the people assigned to his or her team, which for Herrera represented about fourteen hundred households. The homes are grouped into three categories. Priority 1 homes have an elderly person living alone or an individual with a severe disability, an uncontrolled chronic disease, or a high-risk condition; they average three preventive visits a year. Priority 2 homes have occupants with more moderate risk and get two visits a year. The rest are Priority 3 homes and get one visit a year.
That day, Herrera was bringing vaccines to Priority 1 patients who were unable to travel to the clinic. In Atenas, home visits are made on white Honda scooters or off-road motorcycles. In the most remote region, Salas told me, ataps must use boats or even horses to reach some families. We followed Herrera’s scooter in our car, along smoothly paved roads up and down green hills, to our first stop, a one-story stucco house with a fresh coat of yellow paint. Out front was a strange wrought-iron structure—an ornate crate on a chest-high post. Salas explained: you put your garbage bag in the holder on pickup day so street dogs don’t get at it. All the houses had one, each baroquely different from the next.
A middle-aged man ushered us inside. A bookkeeper for local businesses, he lived with and cared for his mother, who had soft, probing eyes and advanced Alzheimer’s. The house had four rooms: two bedrooms, a kitchen, and a bathroom. In the front bedroom, the mother sat on the edge of a hospital bed that almost filled the space. Herrera checked her vital signs, including her temperature and her oxygen level, with a thermometer and a finger sensor from his backpack. He asked her and her son a few questions about how she’d been doing, including after her first vaccine dose, which he’d given her three weeks earlier.
Behind the house, on a stone porch that opened onto a green postage-stamp lawn, Herrera pulled out a rectangle of brown butcher paper, flattened it on a table, and laid out all the vaccination materials. He went to the kitchen sink to wash his hands, using his own soap and paper towels.
Herrera’s visit took about twenty minutes. As we headed down the road, I was struck not only by the efficiency of the visit but also by how ordinary it was: the man had been able to take it for granted that Herrera would visit on a certain day at a certain time to meet certain needs.
I saw this reliability throughout our visits. Because everyone was enrolled with an ebais, everyone was contacted individually about a covid vaccination appointment—most at their neighborhood clinic and a few at home. One woman I met explained that she’d learned about her appointment by phone. I asked her what would happen if the ebais folks didn’t call. She looked at me puzzled. Maybe something was lost in translation. She repeated that she knew what week they would call, and they called. I persisted: What if they didn’t? She’d wait a couple of days and call herself, she said. It was no big deal. She asked me how things worked where I was from. I could only sigh.
One of our visits that morning was to a brick house ringed by purple-flowered crape-myrtle trees. An eighty-year-old woman sat on the porch getting her hair dyed; during the pandemic, her hair stylist was also doing home visits. In a corner bedroom with lots of light, a small man with a regal profile and a shock of white hair was sitting up in a hospital bed, beneath a poster of Jesus. Tubing connected his nasal prongs to a large oxygen tank, its attached water-bubbler faintly audible. Salas recognized the man, who had been his father’s accountant. The man smiled brightly in greeting, but showed no sign of recognition. He had vascular dementia and chronic pulmonary disease.
Up a winding mountain road, we reached a house with a huge mango tree standing sentinel, and dozens of ripe mangoes scattered beneath it. This time it was Salas who was recognized—his father had been the godfather of the seventy-eight-year-old man who lived there, with his wife. To Salas’s delight, the man pointed out a fading, sepia-toned picture of his godfather on the wall. The man, who had congestive heart failure and limited mobility, took the vaccine without complaint.
For each of the households, Herrera keeps an electronic ficha familiar, a family file that provides the primary-care team with remarkably detailed information. This includes medical updates—what ailments have been assessed and what treatments have been administered on any given visit—but also notes on living conditions: whether the floors are dirt or finished, whether there is a refrigerator, a phone, or a computer, and even whether any animals are living “en condiciones insalubres.” According to the C.C.S.S., nearly sixty per cent of Costa Rica’s households have a current, geo-referenced file.
There was nothing magical about the care I saw that day. Herrera wasn’t a saint. But he may have been something better than that: he was the point of contact between a national system and a great many individual lives, seeing to every small detail required for the broader demands of community health.
Salas and I returned to the central clinic, where we met with the medical director of the Atenas Health Area, Carolina Amador. She is in her late forties, with long auburn hair and a quiet, observant air, and she oversees all seven ebais teams. Like Salas, she had wanted to be a doctor since she was in high school. And she, too, took the opportunity offered to Costa Rican medical graduates to spend a year working in an isolated community. It was around the time the ebais system was being launched, and she spent that year helping to provide primary care for an island fishing village, where basic supplies had to be delivered by boat. “I did Pap smears with a flashlight,” she recalled, sitting in her office behind a large wooden desk.
Amador has overseen the Atenas Health Area for seventeen years. She says that the hardest part of her job involves human resources. “People want the director to be their parent, their adviser, their friend, and someone who can get them anything they want,” she said. “I am their psychologist, too. Everyone is motivated differently.”
She wants all the members of her teams to understand that their priority is “the relationship with the community, not just between the physician and patient.” This, she said, is the foundation of the ebais system. There are critical services that have to reach everyone in the community at every stage of life, she explained. Children have regular pediatric visits, starting from the first days of life. Pregnant women have their prenatal and postnatal checks. All adults have tests and follow-up visits to prevent and treat everything from iron deficiency to H.I.V. It’s all free. If people don’t show up for their appointments, she makes sure their team finds out why and figures out what can be done.
Amador described a group program that her staff created for people who have poorly controlled diabetes. They meet on Mondays for two hours in a twelve-week course covering topics from cooking proper meals to administering their insulin. They learn far more than they would in sporadic office visits, and they become a group of peers who know and encourage one another. Amador and her colleagues have documented substantial reductions in blood-sugar levels. That led them to create other groups, including a Zoom forum that was begun as adolescent depression rose during the pandemic—the forum drew ninety teen-agers—and a nutrition program for bus drivers, who have been found to have a high rate of obesity.
Salas was grinning. Everything he had created with his clinic in El Roble, everything he’d tried to build into the ebais system almost three decades ago, had come fully to life in his home town. A generation of professionals like Amador and Herrera had embraced his belief that individual health and public health are inseparable.
Integrating the two has effects that aren’t so visible to patients. I spent the next morning with Mario Quesada, the primary-care physician for an ebais team serving the mountainside neighborhoods of Altos de Naranjo and San Isidro. Each week, he spends three days seeing patients at a clinic halfway up the mountain, and two days at a site on top of the mountain. I visited the one halfway up. It looked much like any other house on the street, which seemed to be the standard design for such clinics. Quesada, who is forty-one, wore a pin-striped, short-sleeved shirt and a microphone headset; during the pandemic, half his appointments have been virtual.
By eight o’clock that morning, he’d already seen three patients—he’d diagnosed a benign rash, a goiter, and an ear infection. The first visit I observed was a telehealth appointment in which he advised a woman with migraines about a change in medication, typing up his notes as they spoke. These were routine visits, and would have been recognizable to primary-care doctors all over the world.
Yet a couple of the visits I observed made apparent the subtle strengths of the ebais approach. One involved, as Quesada put it, “un caso difícil ”—an incontinent sixty-five-year-old woman with schizophrenia. The woman, who lives with her daughter, also has a psychiatrist and a social worker. That day, she needed her prescriptions refilled. But Quesada also saw a note in her ficha familiar about family circumstances which led him to ask her about her supply of diapers. The ebais provides up to forty a month, which was enough until her bowel troubles worsened recently. Quesada suspected that her daughter might not be able to afford more, and learned that the woman was indeed short. He did a quick check of the records and found that another family had returned a box of diapers after an elder died. She could have the box, he said. It was a small thing. But a lack of such basic supplies could mean the breakdown of skin from sitting too long in stool, and lead to infection and wound-care problems. Quesada’s simple reallocation of resources was possible only because he had a bigger picture of the community he serves.
In another telehealth visit, a woman with diabetes and severe hypertension complained that she had been waiting more than a year to get follow-up blood tests. When Quesada consulted her records online, he saw that he had ordered the tests months earlier, but the woman hadn’t shown up for any of them. He told her where to go for her lab tests and filled out the lab orders that she’d need. He could have told her to pick up the order slips, but she’d failed to do that before, too. So Quesada looked through the upcoming appointment list and noticed that a neighbor of hers would be at the clinic soon. He told the woman he’d send her lab orders with the neighbor.
That level of familiarity—the fact that he understood the community around his patient and how it could help—was astounding to me, even as the limitations seemed apparent.
“She’s not going to get her tests done, is she?” I said.
“It’s fifty-fifty,” he said. “One can only do so much. I do my work. They must do theirs.”
In my discussions with clinicians and patients, the weaknesses in the system were not hard to find. With Costa Rica’s constrained resources, there was not enough staffing, especially for specialists. When it came to secondary care, months-long waits for advanced imaging and for procedures were common. People who could afford to do so carried additional insurance for private health care or paid cash to supplement the care that they received from the government. But the ebais system remains immensely popular, and politically untouchable. It has advantages that patients can feel, even if they don’t see all the inner workings.
Near the end of my conversation with Carolina Amador, she explained her approach to the pandemic, and she called up a graph on her computer that showed up-to-the-moment rates of covid cases and deaths by age, sex, and neighborhood. In Angeles, for instance, three per cent of the population had been infected; in Santa Eulalia, nine per cent had been. It was the kind of report I’d seen in the hands of local public-health officials in the United States. They generated these reports, but they hadn’t been given the tools or the authority to act on them directly. Because these officials remain outside the American health-care system, they had to beg providers to respond with adequate testing and vaccination. When that proved insufficient, they were forced to launch their own operations, such as drive-through testing sites and stadium vaccination clinics—and they had to do so from scratch, in a mad rush. The operations were all too delayed and temporary. Here, Amador could see the places with the greatest need and deploy doctors, nurses, and community-health workers to do testing and vaccination. Amid covid, Costa Rica had demonstrated yet again how primary-care leaders could make health happen.
The results are enviable. Since the development of the ebais system, deaths from communicable diseases have fallen by ninety-four per cent, and decisive progress has been made against non-communicable diseases as well. It’s not just that Costa Rica has surpassed America’s life expectancy while spending less on health care as a percentage of income; it actually spends less than the world average. The biggest gain these days is in the middle years of life. For people between fifteen and sixty years of age, the mortality rate in Costa Rica is 8.7 per cent, versus 11.2 per cent in the U.S.—a thirty-per-cent difference. But older people do better, too: in Costa Rica, the average sixty-year-old survives another 24.2 years, compared with 23.6 years in the U.S.
The concern with the U.S. health system has never been about what it is capable of achieving at its best. It is about the large disparities we tolerate. Higher income, in particular, is associated with much longer life. In a 2016 study, the Harvard economist Raj Chetty and his research team found that the difference in life expectancy between forty-year-olds in the top one per cent of American income distribution and in the bottom one per cent is fifteen years for men and ten years for women.
But the team also found that where people live in America can make a big difference in how their income affects their longevity. Forty-year-olds who are in the lowest quarter of income distribution—making up to about thirty-five thousand dollars a year—live four years longer in New York City than in Las Vegas, Indianapolis, or Oklahoma City. For the top one per cent, place matters far less.
In a way, it’s a hopeful finding: if being working class shortens your life less in some places than in others, then evidently it’s possible to spread around some of the advantages that come with higher income. Chetty’s work didn’t say how, but it contained some clues. The geographic differences in mortality for people at lower socioeconomic levels were primarily due to increased disease rather than to increased injury. So healthier behaviors—reflected in local rates of obesity, smoking, and exercise—made a big difference for low earners, as did the quality of local hospital care. Chetty also found that low-income individuals tended to live longest, and have healthier behaviors, in cities with highly educated populations and high incomes. The local level of inequality, or the rates at which people were unemployed or uninsured, didn’t appear to matter much. What did seem to help was a higher level of local government expenditures.
The Costa Rica model suggests that directing those expenditures wisely—in ways attentive to the greatest opportunities for impact—can be transformative when it comes to the less connected and the less advantaged. In an ingenious study, a group of Stanford economists compared families that include a doctor or a nurse with those that do not. The study focussed on Sweden, where, for many years, medical schools used a lottery to select among equally qualified applicants, providing the researchers with a set of otherwise matched families. The study found that people with a medically trained relative were ten per cent more likely to live beyond the age of eighty. Younger relatives were more likely to be vaccinated, were less likely to have drug or alcohol addiction, and had fewer hospital admissions. Older relatives had a lower rate of chronic illnesses such as heart disease. The study even found a “dose response” pattern: the closer that relatives lived to the family health professional, and the closer on the family tree, the larger the benefit. Relationships with people who can supply beneficial knowledge, authority, norms, and encouragement appear to make a major difference in mortality.
There’s no public-health initiative that will add a doctor to your family, but Costa Rica shows that we can provide something close: a primary-care team whom individuals know personally and can call upon in the course of their lives. The country has reduced premature mortality at all income levels, but the largest declines have been at the lower end. In fact, by 2012 Costa Rica had largely eliminated disparities in infant mortality based on how much money families have or where they live. (In the U.S., babies born in high-poverty counties are almost twice as likely to die in their first year of life as those born in low-poverty counties—and it’s a similar story for those born in rural instead of suburban areas.)
Other countries, including Sri Lanka and Colombia, have taken notice, and begun adopting key elements of the Costa Rica model. There’s no reason a U.S. city or state couldn’t do so, too. As the pandemic ebbs, countries will be assessing what went wrong with their public-health systems. A fundamental failure has been the separation of public health from health-care delivery. Getting that right, across the globe, could present our greatest opportunity to secure longer and better lives.
What would this model look like in the United States? Consider the example of one common illness, viral hepatitis. Infection with either the hepatitis-B or the hepatitis-C virus can lead to severe liver damage and to chronic liver disease—a top-five cause of death for Americans between the ages of forty-five and sixty-four. It can also lead to liver cancer. More than four million people in the U.S. have a chronic hepatitis-B or hepatitis-C infection. Hepatitis C alone is the most common reason that American patients require liver transplants. We spend billions of dollars a year on treatment for these two viruses.
I know the damage that viral hepatitis can do. My aunt, a former family physician in the Washington, D.C., area, slowly died from liver failure after contracting hepatitis B through an accidental needle stick in the nineteen-eighties. Today, we have an effective vaccine against hepatitis B, and hepatitis C has become curable with oral medications. If we had a system that let us expand screening, treatment, and vaccination, we could eliminate these diseases. Indeed, in 2017 the Department of Health and Human Services set that as a goal.
But here again our system is designed for the great breakthrough, not the great follow-through. In Costa Rica, nearly ninety per cent of babies are vaccinated against hepatitis B at birth. (Mother-to-child transmission during childbirth is a significant pathway for infection.) In the U.S., only two-thirds are. Just twenty-five per cent of American adults are vaccinated against the virus. Our chronic-liver-disease rates have barely budged. In the meantime, new hepatitis-C infections have increased by almost thirty per cent since 2017. If every community had a primary-care team able to provide visits to all residents, we’d have a way to see that everyone had been offered vaccination and other preventive measures, screening for viral hepatitis, and prompt treatment for those found to have it. Viral hepatitis is markedly higher among immigrant Asian residents, African Americans, the poor, and intravenous drug users—precisely the people who have had the greatest difficulty in gaining access to medical care and advice.
We know what needs to be done; we just don’t have the mechanisms to do it. Yet we’ve had glimpses of what we can accomplish with the right system in place. In the nineteen-nineties, the U.S. government launched a national effort to offer hepatitis-B vaccinations to all hospital workers, and, by the middle of the decade, two-thirds of them had got the jab; infections in this population were reduced by a remarkable ninety-eight per cent, from seventeen thousand cases in 1983 to just four hundred in 1995. How? Our hospital systems have dedicated personnel who get in touch with each of their employees at least once a year and offer them essential preventive care, including vaccinations, without charge. Yet those systems aren’t equipped to do the same for the people in the communities they serve. Costa Rica shows how they could be.
“You have to come to this place with me,” Salas said on my last day in Costa Rica. I’d been hoping to spend more time in the clinic with the primary-care doctors, and wasn’t pleased that he’d decided on a visit to another coffee town—Palmares, a half hour’s drive from Atenas through the mountains.
“What’s there?” I asked.
“A dental program,” he said. Responding to my skeptical look, he went on, “I’ve heard such good things about it. We will go.” He was still, decades on, a persuasive man.
We arrived at the parking lot of a coffee-processing plant, and found a powder-blue bus with a big cartoon molar and a fat loop of cartoon floss on the door. On the side, in big block letters, it said, “¡juntos construimos sonrisas!”—“Together we build smiles!” I was greeted by Alejandra Rodríguez, a white-coated dentist, who told me that the bus was donated by Chick-fil-A, which gets coffee beans from the Palmares plant. Inside, the bus was outfitted with three dental chairs, an X-ray machine, and enough supplies to provide dental cleanings and treatment for all the schoolchildren in the community.
Dental care was not a significant part of the ebais structure that Salas helped design. But its systemic approach took root more widely. As Rodríguez explained to me, members of her profession helped lead an effort, starting in the nineteen-eighties, to institute after-lunch toothbrushing in elementary schools. Toothbrushes were provided for every student; rows of sinks were installed at schools, so that groups of children could brush at the same time. The program insured that all schoolchildren brushed their teeth at least once a day. The effort began in and around Palmares, and soon the idea was implemented across the country. Meanwhile, the Ministry of Health required that table salt be fluoridated—an easier way to introduce fluoride on a national scale than fluoridating every town’s water supply.
The results of such measures have been dramatic. In 1980, Costa Ricans averaged more than nine teeth decayed, missing, or filled by the age of twelve. By 2002, the number was below two. Today, it is below one—results as good as America’s or better, at a fraction of our costs.
Rodríguez wanted to show us the new program she’s leading. Throughout the school year, the blue bus visits all nine elementary schools in Palmares, providing cleanings and treatment for every child whose parents permit it. On board, Salas and I saw a skinny sixth-grade boy have his teeth cleaned and get a sealant applied to his molars.
Costa Ricans, it now struck me, had some of the best teeth I’d seen anywhere in my travels. Rodríguez and her partners were showing how dental care could be improved even further. They were integrating public health and individualized care—creating an actual health system—even in dentistry.
“It is possible to change the picture,” Salas said to me afterward, reflecting on our visits inside the system he’d helped create so long ago. “It is possible to call upon a group of people, a group of Quixotes—do you know Quixote?—who think and can see twenty years, thirty years ahead. It is possible to raise an idea and see it supported by a younger generation to become real.”
Public health can be a bulwark against the cynicism that public institutions sometimes inspire. Yet acceptance, Salas knew, always has to be earned. He recalled how anxious his grandmother was when the government first instituted a social-security contribution. “Because for the first time she had to pay something for the workers,” he said. “I remember she said to us, ‘The coffee harvest is good but not so good as to have money to pay workers now for social security.’ ” Every step is hard-fought.
When Salas and I had walked through the cemetery, shortly after my arrival in Atenas, we’d stopped at his family plot, among the oldest there. His great-grandfather Guillermo, who died at forty-five, in 1894, and his great-grandmother Avelina, who died at sixty-five, in 1925, were buried there. In the next generation, his grandfather Emilio also died young, at forty-six, in 1931. Death seemed to take family members at random. His grandmother Guillerma lived to ninety-seven, but two of her children had died in infancy—one at sixteen months, from a respiratory illness that Salas suspected was whooping cough, and the other at twenty-four months, from diarrhea. In 1986, Salas buried his father, Emilio Salas Villalobos, in the plot, after his death, from colon cancer, at the age of seventy-four. In 2001, he buried his mother, Sara Chaves Villalobos, who also died at seventy-four, from a heart attack.
I noticed that his mother’s name wasn’t on the family grave marker, and I asked him why.
“I am responsible for not including my mother’s name and date,” he told me. “Possibly, I am waiting for the opportunity for writing our names and dates together, and forever.” Álvaro Salas Chaves is seventy years old now, and he imagines he might be joining her soon.
But, owing to a health system he helped build, the average Costa Rican his age will live at least another sixteen years. Salas is sturdy, with no serious illnesses. Still, when the time comes, he intends to be buried in the same plot.
“Because all of my family are here,” he explained. “They are all around. We will have a big meeting here.” ♦
Published in the print edition of the August 30, 2021, issue, with the headline “The Costa Rica Model.”
Atul Gawande, a professor of public health and a surgeon, is the founder and chair of Ariadne Labs. He was recently nominated to be the assistant administrator for global health at the U.S. Agency for International Development.
A Pill to Make Exercise Obsolete
What if a drug could give you all the benefits of a workout?
By Nicola TwilleyOctober 30, 2017
The molecular changes caused by physical exertion are still poorly understood.Illustration by Jack Sachs
It was late summer, and the gray towers of the Salk Institute, in San Diego, shaded seamlessly into ocean fog. The austere, marble-paved central courtyard was silent and deserted. The south lawn, a peaceful retreat often used for Tai Chi and yoga classes, was likewise devoid of life, but through vents built into its concrete border one could detect a slight ammoniac whiff from more than two thousand cages of laboratory rodents below. In a teak-lined office overlooking the ocean, the biologist Ron Evans introduced me to two specimens: Couch Potato Mouse and Lance Armstrong Mouse.
Couch Potato Mouse had been raised to serve as a proxy for the average American. Its daily exercise was limited to an occasional waddle toward a bowl brimming with pellets of laboratory standard “Western Diet,” which consists almost entirely of fat and sugar and is said to taste like cookie dough. The mouse was lethargic, lolling in a fresh layer of bedding, rolls of fat visible beneath thinning, greasy-looking fur. Lance Armstrong Mouse had been raised under exactly the same conditions, yet, despite its poor diet and lack of exercise, it was lean and taut, its eyes and coat shiny as it snuffled around its cage. The secret to its healthy appearance and youthful energy, Evans explained, lay in a daily dose of GW501516: a drug that confers the beneficial effects of exercise without the need to move a muscle.
Exercise has its discomforts, after all: as we sat down to talk, Evans, a trim sixtysomething in a striped polo shirt, removed a knee brace from a coffee table, making room for a mug of peppermint tea; he was trying to soothe his stomach, having picked up a bug while hiking in the Andes. Evans began experimenting with 516, as the drug is commonly known, in 2007. He hoped that it might offer clues about how the genes that control human metabolism are switched on and off, a question that has occupied him for most of his career.
Mice love to run, Evans told me, and when he puts an exercise wheel in their cage they typically log several miles a night. These nocturnal drills are not simply a way of dealing with the stress of laboratory life, as scientists from Leiden University, in the Netherlands, demonstrated in a charming experiment conducted a few years ago. They left a small cagelike structure containing a training wheel in a quiet corner of an urban park, under the surveillance of a motion-activated night-vision camera. The resulting footage showed that the wheel was in near-constant use by wild mice. Despite the fact that their daily activities—foraging for food, searching for mates, avoiding predators—provided a more than adequate workout, the mice voluntarily chose to run, spending up to eighteen minutes at a time on the wheel, and returning for repeat sessions. (Several frogs and slugs also made use of the amenity, possibly by accident.)
Still, as the example of Lance Armstrong Human makes clear, sometimes exercise alone is not enough. When Evans began giving 516 to laboratory mice that regularly used an exercise wheel, he found that, after just four weeks on the drug, they had increased their endurance—how far they could run, and for how long—by as much as seventy-five per cent. Meanwhile, their waistlines (“the cross-sectional area,” in scientific parlance) and their body-fat percentage shrank; their insulin resistance came down; and their muscle-composition ratio shifted toward so-called slow-twitch fibres, which tire slowly and burn fat, and which predominate in long-distance runners. In human terms, this would be like a Fun-Run jogger waking up with the body of Mo Farah. Evans published his initial results in the journal Cell, in 2008. This year, he showed that, if his cookie-dough-scarfing mice were allowed to exercise, the ones that had been given 516 for eight weeks could run for nearly an hour and half longer than their drug-free peers. “We can replace training with a drug,” he said.
The drug works by mimicking the effect of endurance exercise on one particular gene: PPAR-delta. Like all genes, PPAR-delta issues instructions in the form of chemicals—protein-based signals that tell cells what to be, what to burn for fuel, which waste products to excrete, and so on. By binding itself to the receptor for this gene, 516 reconfigures it in a way that alters the messages the gene sends—boosting the signal to break down and burn fat and simultaneously suppressing instructions related to breaking down and burning sugar. Evans’s doped mice ran farther, in part because their muscles had been told to burn fat and save carbohydrates, which meant that they took longer to “hit the wall”—the painful sensation encountered when muscles exhaust their glucose store.
In dozens of other ways, 516 triggers biochemical changes that take place when people train for a marathon—changes that have substantial health benefits. Evans refers to the compound as “exercise in a pill.” But although Evans understands the mechanism behind 516’s effects at the most minute level, he doesn’t know what molecule triggers that process naturally during exercise. Indeed, one of the most significant challenges facing anyone who wants to develop an exercise pill is that the biological processes unleashed by physical activity are still relatively mysterious. For all the known benefits of a short loop around the park, scientists are, for the most part, incapable of explaining how exercise does what it does.
The compound 516 was developed in the late nineties, in the laboratories of GlaxoSmithKline. Its creator, a chemical biologist named Tim Willson, was in charge of a research group tasked with prospecting for chemicals that could bind to the PPAR-delta receptor. The search had been prompted by an earlier discovery: compounds that bound to a similar gene receptor were highly effective in treating diabetics, the pharmaceutical industry’s most lucrative market. Willson’s team tested 516, first in a test tube and then on middle-aged, obese monkeys, and the results were exciting. “We got this dramatic increase in good cholesterol, and a commensurate decrease in the bad kind,” he told me recently, noting that 516 also lowered insulin levels and triglycerides. The combination of effects made 516 seem like a promising treatment for what’s known as “metabolic syndrome,” a cluster of symptoms—including obesity, high blood pressure, and high blood sugar—that is a precursor to heart disease and diabetes. More than a third of adult Americans are estimated to have metabolic syndrome, which made 516’s potential profits seem rather attractive. GlaxoSmithKline took the drug all the way through Phase II clinical trials in humans, successfully demonstrating that it lowered cholesterol levels without any problematic side effects.
But, in 2007, GlaxoSmithKline decided to shelve 516. The company was about to embark on Phase III trials—the large, expensive, double-blind, placebo-controlled trials that are required for F.D.A. approval—when the results of a long-term-toxicity test came in. Mice that had been given large doses of the drug over the course of two years (a lifetime for a lab rodent) developed cancer at a higher rate than their dope-free peers. Tumors appeared all over their bodies, from the tongue to the testes. The results made GlaxoSmithKline’s decision all but inevitable. If a large dose of the drug seemed to increase the risk of cancer at the end of a mouse lifespan, the only way to conclusively prove that even a lower dose would not have a similar effect on humans would be to run a seventy-year trial. Without that proof, the F.D.A. would likely judge the potential risks of taking the drug to be greater than the actual dangers of high cholesterol.
Elsewhere, however, work on 516 persisted. Because Willson, in 2001, had published his description of the chemical’s structure and clinical effects, other labs were able to synthesize the chemical for research use. Ron Evans began his work on 516 at Salk the same year that GlaxoSmithKline’s researchers abandoned theirs. Since then, he has developed a less potent version that he hopes will also be less toxic.
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And 516 is not the only “exercise pill” in development. At the University of Southampton, on England’s south coast, I met with a chemical biologist named Ali Tavassoli, a lanky, youthful forty-two-year-old with a chilled-out demeanor, which gives way to geeky enthusiasm when he starts explaining the particulars of protein interactions. Tavassoli came across his drug, Compound 14, more or less by chance, while designing a way to screen a new class of cancer drug, and he still seems somewhat bemused by the fact that his lab is now a front-runner in the race to develop an exercise pill. In a recent paper, he and his colleagues showed that Compound 14 caused the blood-glucose levels of obese, sedentary mice on a high-fat diet to approach normal levels in just a week, while melting away five per cent of their body weight. It works, he explained, by fooling cells into thinking that they are running out of energy, causing them to burn through more of the body’s fuel reserves.
Meanwhile, in Boston, Bruce Spiegelman, a Harvard cell biologist, has discovered two potent exercise hormones. One of them, irisin, turns metabolically inert white fat in mice into mitochondria-packed, energy-burning brown fat, and Spiegelman said that he’s seen evidence that it may also boost levels of healthy proteins in the area of the brain associated with learning and memory. He is now researching a third compound, and when I visited his lab he invited me to look through a microscope at a petri dish of sleek, round muscle fibres—a kind of mouse tartare—awaiting treatment with the chemical. They were twitching spasmodically. “It’s spontaneous,” Spiegelman said, as I recoiled. “The membranes are electrically active, and it’s almost like static on a radio. They just fire occasionally.” The experiment—effectively, exercise in a dish—is an efficient way of screening a large number of chemicals before selecting the most promising candidates for trials on intact mice.
I noticed that the fibres were a deep red, almost like raw tuna, and Spiegelman explained that this is a familiar property of slow-twitch muscle, the fat-burning, fatigue-resistant kind called upon during endurance training. Fast-twitch muscle, which is more powerful but tires quickly, and which runs on carbohydrate, is pinker. The piscine comparison is not incidental. During his research, Spiegelman discovered that tuna have a mutation in a gene that plays an important role in determining muscle-fibre ratios. As a result, all the muscle in tuna is slow-twitch, which is the reason for the distinctive color and meaty texture of a tuna steak. Spiegelman is now collaborating with other researchers with the goal of inserting the tuna version of that gene into easily farmed fish, such as carp or salmon, in order to “tunafy” them and thus ease demand for wild bluefin.
Although Spiegelman, Evans, and Tavassoli study different compounds, they have all followed what could be described as the metal-detector method of exercise-pill development: scanning thousands of chemicals in order to find one or two that convey some of the benefits of exercise. Other researchers are tackling the problem from the opposite direction—attempting to document all the biochemical reactions that exercise unleashes, which will create a sort of road map for drug development. Next year, the National Institutes of Health will embark on an ambitious five-year study to measure every major molecule changed by exercise in approximately three thousand people of both sexes and all age groups, and with a variety of preëxisting fitness levels. Maren Laughlin, who is leading the program, explained that the technology to create a molecular snapshot of the human body in motion has only become available in the past decade. “We’ve studied human metabolism for many, many years, but almost always at rest,” she said. It is as if our knowledge of how the brain works had come from observing only people who were asleep.
In Australia, a biologist named David James recently took the first step in this direction, studying muscle biopsied from four young, healthy men before and after ten minutes of flat-out cycling on an exercise bike. James and his colleagues itemized every measurable difference in protein structure between the before and after samples. They found more than a thousand changes, of which only ten per cent can be explained by current medical science. For anyone wanting to develop an exercise pill, these new data are both promising and daunting. “You know, people talk about exercise mimetics,” James said. “But what are you going to mimic?”
The red double-decker buses of London are famous around the world. Less well known is the fact that the first quantitative, systematic medical study of exercise took place aboard them. In the late nineteen-forties, a young British epidemiologist named Jerry Morris was looking through the postmortem folios of a hospital in the East End when he noticed an alarming increase in the frequency of heart attacks during the first half of the twentieth century. Others had seen the same trend but nobody had an explanation. Morris, however, suspected that the frequency of heart attack might correlate with sedentary occupations, and so he turned to the double-decker bus. “If you’ve been to London, then you know,” Bill Hayes, a writer and photographer who is at work on a history of exercise, told me. “The driver sits at the front and drives the bus, and the conductor hops on and off the bus and climbs up and down the stairs taking tickets and getting people to their seats.” Of the thousands of drivers and conductors working on London’s buses at the time, the vast majority were men, and most came from a similar social background. The only substantial difference between them, in aggregate, was their daily activity levels.
Morris spent hours on buses, monitoring how much time the drivers spent sitting (ninety per cent of their shift, on average) and counting the numbers of steps the conductors climbed each day (between five hundred and seven hundred and fifty). Then, with the help of Britain’s newly established National Health Service, he went through the busmen’s medical records. Morris was stunned by how powerfully the data bore out his initial hypothesis: the sedentary drivers were almost twice as likely as the mobile conductors to drop dead of a sudden heart attack. He followed up with what he described as an “epidemiology of uniforms”—a painstaking comparison of the waist size of trousers issued to both groups, at every age—which established that drivers were significantly bulkier around the midsection than their conductor peers. Morris later confirmed a similar correlation in postal workers, with sedentary counter clerks showing a much higher incidence of cardiovascular disease than postmen, who did their rounds on foot or by bike.
When the papers presenting these findings appeared in The Lancet, Morris’s conclusion—that exercise was medically important and that its absence resulted in death and disease—was met with surprise and even disbelief. “Puzzling,” the Aberdeen Evening Express declared, noting that Morris’s studies failed to take into account what were then generally accepted risk factors for heart attack, such as a temperamental propensity toward “nervous strain.” Mainstream medical wisdom held that heart attacks were most likely the result of high blood pressure, and that physical activity had nothing to do with either.
Up to this point, historical attitudes toward exercise had varied, according to Hayes. The Ancient Greeks were fans. Plato, a former competitive wrestler, praised the mental-health benefits of physical exertion, and Hippocrates wrote, “Eating alone will not keep a man well, he must also take exercise.” By contrast, medieval Europeans tended to regard the body as a vessel for sin, and exercise as a distraction from the more important work of improving the soul. “The spirit flourishes more strongly and more actively in an infirm and weakly body,” the twelfth-century French abbot St. Bernard of Clairvaux assured his followers. Avicenna, a Persian scientist whose view of bodily health was substantially more enlightened than that of his European contemporaries, took an intermediate view—advocating moderate exercise but warning of the dangers posed by its heating effects and its capacity to spread preëxisting impurities throughout the body.
There also seemed to be some confusion about what exercise actually was. Hayes mentioned “De Arte Gymnastica,” a 1569 treatise by an Italian nobleman named Girolamo Mercuriale, which is considered the first book on sports medicine. The forms of exercise Mercuriale discussed included being a passenger in a boat rowed by someone else. “It’s kind of sweet,” Hayes said. “He believed that because it causes movement and movement had an effect on the humors within the body, it would be a good thing.” Until the Victorian era, when sporting activity came to be regarded as a moral safeguard against dissipation, vigorous exercise was still cautioned against, particularly in the case of women. It was thought to lead to strain, fatigue, and even untimely death.
Of course, for most people, through most of human history, not moving has not been an option. The illustrated exercises in “De Arte Gymnastica” were aimed at Renaissance princelings; the feudal peasants laboring on the nobility’s vast estates could hardly avoid sustained and strenuous activity. Only since industrialization, which made physical exertion a choice rather than a necessity, have scientists begun to quantify its virtues—and, in the process, to increase the burden of guilt on those who fail to squeeze in enough of it around the constraints of their sedentary jobs.
In the sixty years following Morris’s pioneering work, the benefits of exercise have been measured in study after study. Researchers soon silenced any remaining doubts over Morris’s findings, repeatedly demonstrating that physical activity helped reduce deaths from heart disease and stroke. Subsequent studies—examining, variously, twins, the Amish, Danish workers forced to take the elevator, and Dallas students prescribed bed rest—showed that a lack of exercise was tied to the early onset of more than forty chronic diseases or conditions, from constipation and colon cancer to depression and diabetes. Today, more than a hundred thousand published papers testify to the connection between exercise and health. Barely a week goes past without a headline linking exercise to stronger bones, a reduced risk of dementia, the ability to learn new languages, and, of course, better sex. Countless institutions, including the World Health Organization and the Centers for Disease Control, recommend at least a hundred and fifty minutes of exercise a week. Such is the weight of medical evidence that, if something could be developed to safely mimic the benefits of exercise, it would likely be the most valuable pharmaceutical in the world. Yet, at the same time, the sheer range of those benefits suggests that it is unlikely that any single drug could have such wide-ranging effects.
The real problem, according to Ron Evans, lies in the term “exercise,” which is too general to be useful. “You have to be more granular about it,” he told me. He suspects that a mere handful of biochemical pathways will prove to be responsible for the majority of exercise’s benefits. Among the current field of exercise-pill competitors, Evans is the closest to the finish line. He has set up a company, Mitobridge, to take his improved version of 516 to market; this summer, it launched Phase I trials in humans.
The F.D.A. doesn’t currently recognize metabolic syndrome, let alone lack of exercise, as a disease. Anyone who wants to market an exercise pill must therefore get it approved as a treatment for a disease that does meet the F.D.A.’s criteria, in the hope that, once it is on the market, its use will spread to encompass a wider range of conditions. Evans pointed out that statins were initially approved, in the late eighties, specifically for people who had had a heart attack; three decades later, they’re routinely prescribed for tens of millions of people who have only high cholesterol. With this example in mind, Mitobridge is testing its drug as a treatment for Duchenne Muscular Dystrophy, an incurable genetic disease that affects one in five thousand males, causing their muscles to break down and leading inexorably to death at an average age of twenty-six. “The economics of getting a drug approved make Duchenne a good target,” Evans said. “It’s a disease for which there are no good drugs, and the kids who have it will all die young. That’s an easier sell to the F.D.A.”
Even if everything goes smoothly, however, 516 is multiple trials and several years away from reaching the market. And although Evans is convinced that his improved version of the drug is safe, any molecule that affects metabolic processes is necessarily interacting with a variety of other molecules throughout the body, in ways that we don’t yet understand. Nonetheless, Evans, James, and Spiegelman are all confident that legal drugs mimicking some of the effects of exercise are on their way, sometime within the next ten to fifteen years. Ali Tavassoli, the Southampton researcher, is more skeptical. “Newspapers, the media—they always get me in to be the cynical Brit on this one,” he said, laughing at the gung-ho attitude of his American colleagues. His main work lies in cancer research, and he is all too aware that dramatic changes in cell metabolism are linked to the growth of tumors. His fear is that artificially increasing the rate at which muscle cells burn energy cannot help but have long-term consequences elsewhere in the body. “Not all of them are going to be good news,” he said.
All drugs have risks: the issue is whether the possible benefits make the risks worthwhile. For someone with Duchenne, taking 516 would make perfect sense. There are a handful of other contexts where a short course of an exercise pill could be extremely useful. Astronauts, for example, routinely spend two hours a day exercising on equipment designed to mitigate muscle atrophy and bone loss caused by low gravity, but they still return to Earth after a six-month space-station stint with mild osteoporosis and significantly weakened muscles. Other people for whom an exercise pill might be a gamble worth taking include patients recovering from surgery or attached to a ventilator. Then, there are the elderly. After the age of forty, all of us, even the athletic, lose about eight per cent of our muscle mass each decade, with a further fifteen-per-cent decline between the ages of seventy and eighty. The resulting frailty can be lethal: nearly half of seniors hospitalized for a hip fracture never go home.
The cost-benefit analysis becomes murkier in the case of the estimated eighty per cent of American adults who do not get their recommended hundred and fifty minutes of exercise each week. From a public-health perspective, physical inactivity is one of the most significant problems of the twenty-first century. One recent study found that, of all the deaths in Europe in 2008, seven per cent could be attributed to inactivity—more than twice as many as were caused by obesity. “So which is better for those people?” Willson, the original developer of 516, asked me. “Being told—again—to exercise for thirty minutes a day, or taking a pill?”
One could respond with another question: Why can’t humans just be more like mice? Why do so many of us choose to skip exercise in favor of watching TV or catching up on e-mail? I talked to Theodore Garland, a biologist at the University of California, Riverside, who has studied variations in voluntary physical activity between species. He pointed to theories that much of human development has been motivated by the imperative to conserve energy, and suggested that, over evolutionary time, different species tend to develop neurochemical reward systems that make movement more appealing, or less, based on their survival needs. Instead of designing a pill to replace exercise in humans, Garland favors a different pharmaceutical solution. “Personally, I’ve been more interested in the possibility of drugs that would make us more motivated to exercise,” he said.
Ataste for exercise, I gradually realized, was something that all the pill researchers had in common. Spiegelman follows a strict regimen of kickboxing, running, and lifting weights. Tavassoli is a surfer and rock climber; Evans and James are cyclists. Willson is a triathlete, who recently completed his eleventh Half Ironman. “I train because that’s part of the way I live,” he said “It’s part of my personality. I love that discipline of having to exercise regularly.” Taking a pill, he said, would feel like cheating.
“In a lot of people’s eyes, the development of an exercise pill is a bad thing,” Evans said. “They say we’re trying to undermine exercise in America.” The more accurate charge is that Evans’s research may redefine exercise—for better and for worse—in much the same way that other fields of metabolic research have gradually redefined food. During the nineteenth and twentieth centuries, as scientists discovered vitamins, minerals, and phytochemicals, “food” was transformed into “nutrients.” That conceptual shift paved the way for dietary pyramids, labelling laws, the rise of so-called superfoods, and even wholesale food replacements such as Soylent. In the coming years, as research provides us with new ways of understanding and quantifying physical activity, our relationship with exercise will surely change. A morning jog will be reclassified as a good source of beneficial chemicals; sports may be redesigned to optimize their molecular outcomes. A scientific understanding of the parts may well come at the expense of appreciating the immeasurable whole.
Although 516 has not been approved as a drug, plenty of people are taking it. Once the structure of a new compound has been published, chemical-supply laboratories are free to synthesize it for sale, “for research purposes only.” 516 is easy and relatively cheap to make, and it is readily available online. The earliest adopters were élite athletes looking for an edge. The World Anti-Doping Agency added 516 to its list of prohibited substances in 2009, and testing for it is now routine. Since then, at least six professional cyclists have been suspended after being caught taking the drug. More recently, 516 has become popular among the kind of men—and they are almost all men—who frequent messages boards with names like “Think Steroids,” “Swol HQ,” and “Juiced Muscle.” All across this peculiar corner of the Internet, guys whose avatars typically feature headless selfies in body-building poses are dosing themselves with 516 and sharing their reactions—usually anonymously, using such screen names as Macho313, nofatchix, and Big Beef.
I joined a couple of forums to ask these men about their experiences using 516. Most were unwilling to talk, let alone be identified, but eventually a member of the MuscleChemistry.com forum agreed to correspond with me, on the condition that I refer to him only by his online handle, Iron Julius. He told me that he lived in a small town in the South and was a father of three. He began taking the drug sometime in 2012, having heard about it on another board. “It wasn’t yet very popular but the little info there was made it sound like something I might like,” he wrote. Iron Julius’s wife had been nagging him to start running with her, but his bulk made him hesitate. Still, he signed up for a five-kilometre race, mostly to support her. He started taking 516 five days before the race. “I was just planning to walk a good bit,” he wrote. “But I actually ran with her the entire time. It blew my mind how good I felt.”
Iron Julius still takes 516, although lately he has noticed a decrease in the drug’s quality. “I’m a volunteer firefighter so stamina at times is very important,” he explained. “If you research, many police and firefighters are on some form of performance-enhancing substance as the jobs are sometimes physically demanding.” Iron Julius told me that around a third of the people he sees at the gym are using 516, without any side effects that he’s heard about. When I asked whether he would recommend it, his response was, “Hell yeah man, try it. It don’t mess with hormones and it increases performance.”
So I ordered some. A few weeks later, a twenty-milligram bottle of 516 arrived, taped into a sealed Tyvek envelope. It was about the size of the complimentary shampoo you get in hotels and contained a cloudy white liquid with a faint smell of nail-polish remover. A label instructed me to “see accompanying information”—there wasn’t any—for dosage instructions. Below that were two contradictory phrases: “Rx only” and “Not for human consumption.”
I called Tim Willson, the drug’s designer, to ask whether he would take it. “No,” he said, without hesitation. I contacted the other researchers and found that none of them had ever taken an exercise pill, in any form. I put the bottle to one side of my desk while I pondered not only the advisability of ingesting a likely carcinogen but also the fact that I actually enjoy exercise and get plenty of it. Since then, the bottle has sat on my desk, undisturbed. During the past month, its contents appear to have developed a faint, yellowish tinge. ♦Published in the print edition of the November 6, 2017, issue, with the headline “The Exercise Pill.”
Nicola Twilley, a frequent contributor to The New Yorker, co-hosts the podcast “Gastropod.” She is the author, with Geoff Manaugh, of “Until Proven Safe: The History and Future of Quarantine.”More:DrugsExerciseSalk InstitutePillsWorkoutsMice
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