MatterIt’s not just a modern problem. Airborne toxins are so pernicious that they may have shaped human evolution. A fire burned in Bargo, Australia, about 90 miles southwest of Sydney in December.Credit…Peter Parks/Agence France-Presse — Getty ImagesJan. 13, 2020Updated 3:43 p.m. ETThe threat of air pollution grabs our attention when we see it — for example, the tendrils of smoke of Australian brush fires, now visible from space, or the poisonous soup of smog that descends on cities like New Delhi in the winter.But polluted air also harms billions of people on a continuing basis. Outdoors, we breathe in toxins delivered by car traffic, coal-fired plants and oil refineries. Indoor fires for heat and cooking taint the air for billions of people in poor countries. Over a billion people add toxins to their lungs by smoking cigarettes — and more recently, by vaping. Ninety-two percent of the world’s people live in places where fine particulate matter — the very small particles most dangerous to human tissues — exceeds the World Health Organization’s guideline for healthy air. Air pollution and tobacco together are responsible for up to 20 million premature deaths each year.Airborne toxins damage us in a staggering number of ways. Along with well-established links to lung cancer and heart disease, researchers are now finding new connections to disorders such as diabetes and Alzheimer’s disease.Scientists are still figuring out how air pollution causes these ailments. They are also puzzling over the apparent resilience that some people have to this modern onslaught.Some researchers now argue that the answers to these questions lie in our distant evolutionary past, millions of years before the first cigarette was lit and the first car hit the road.Our ancestors were bedeviled by airborne toxins even as bipedal apes walking the African savanna, argued Benjamin Trumble, a biologist at Arizona State University, and Caleb Finch of the University of Southern California, in the December issue of the Quarterly Review of Biology. Our forebears evolved defenses against these pollutants, the scientists propose. Today, those adaptations may provide protection, albeit limited, against tobacco smoke and other airborne threats.But our evolutionary legacy may also be a burden, Dr. Trumble and Dr. Finch speculated. Some genetic adaptations may have increased our vulnerability to diseases linked to air pollution.It is “a really creative, interesting contribution to evolutionary medicine,” said Molly Fox, an anthropologist at the University of California, Los Angeles, who was not involved in the new study.The story begins about seven million years ago. Africa at the time was gradually growing more arid. The Sahara emerged in northern Africa, while grasslands opened up in eastern and southern Africa.The ancestors of chimpanzees and gorillas remained in the retreating forests, but our ancient relatives adapted to the new environments. They evolved into a tall, slender frame well suited to walking and running long distances.Dr. Finch and Dr. Trumble believe that early humans faced another challenge that has gone largely overlooked: the air.Periodically, the savanna would have experienced heavy dust storms from the Sahara, and our distant ancestors may have risked harm to their lungs from breathing in the silica-rich particles.“When the dust is up, we’re going to see more pulmonary problems,” Dr. Finch said. Even today, Greek researchers have found that when Sahara winds reach their country, patients surge into hospitals with respiratory complaints.The dense foliage of tropical forests gave chimpanzees and gorillas a refuge from dust. But the earliest humans, wandering the open grasslands, had nowhere to hide.Dust was not the only hazard. The lungs of early humans also may have been irritated by the high levels of pollen and particles of fecal matter produced by the savanna’s vast herds of grazing animals.Dr. Finch and Dr. Trumble maintain that scientists should consider whether these new challenges altered our biology through natural selection. Is it possible, for instance, that people who are resilient to cigarette smoke have inherited genetic variants that protected their distant ancestors from cave fires?One way to answer these questions is to look at genes that have evolved significantly since our ancestors moved out of the forests.One of them is MARCO, which provides the blueprint for production of a molecular hook used by immune cells in our lungs. The cells use this hook to clear away both bacteria and particles, including silica dust.The human version of the MARCO gene is distinctively different from that of other apes. That transformation happened at least half a million years ago. (Neanderthals carried the variant, too.) Breathing dusty air drove the evolution of MARCO in our savanna-walking ancestors, Dr. Finch and Dr. Trumble hypothesize.Later, our ancestors added to airborne threats by mastering fire. As they lingered near hearths to cook food, stay warm or keep away from insects, they breathed in smoke. Once early humans began building shelters, the environment became more harmful to their lungs.“Most traditional people live in a highly smoky environment,” Dr. Finch said. “I think it has been a fact of human living for us even before our species.”Smoke created a new evolutionary pressure, he and Dr. Trumble believe. Humans evolved powerful liver enzymes, for example, to break down toxins passing into the bloodstream from the lungs.Gary Perdew, a molecular toxicologist at Penn State University, and his colleagues have found evidence of smoke-driven evolution in another gene, AHR.This gene makes a protein found on cells in the gut, lungs and skin. When toxins get snagged on the protein, cells release enzymes that break down the poisons.Other mammals use AHR to detoxify their food. But the protein is also effective against some of the compounds in wood smoke.Compared to other species, the human version produces a weaker response to toxins, perhaps because AHR protein is not the perfect protector — the fragments it leaves behind can cause tissue damage.Before fire, our ancestors did not need to use AHR very often; in theory, their bodies could tolerate the limited damage the protein caused.But when we began breathing smoke regularly and needing the AHR protein constantly, the gene might have become dangerous to our health.Dr. Perdew believes that humans evolved a weaker AHR response as a way to find “a sweet spot,” a compromise that minimized the damage of airborne pollutants without causing too many side effects.These adaptations were never perfect, as evidenced by the fact that millions of people still die today from indoor air pollution. But evolution doesn’t seek perfect health. “All that matters from an evolutionary standpoint is that you reproduce,” Dr. Perdew said. “If you die in your forties, so what? It’s kind of a cold, heartless way to think about it, but it is what it is.”A changed atmosphereOur species arrived at the Industrial Revolution two centuries ago with bodies that had been shaped for millions of years by this highly imperfect process.Clean water, improved medicines and other innovations drastically reduced deaths from infectious diseases. The average life expectancy shot up. But our exposure to airborne toxins also increased.“If we compressed the last five million years into a single year, it wouldn’t be until Dec. 31, 11:40 p.m., that the Industrial Revolution begins,” Dr. Trumble said. “We are living in just the tiniest little blip of human existence, yet we think everything around us is what’s normal.”The Industrial Revolution was powered largely by coal, and people began breathing the fumes. Cars became ubiquitous; power plants and oil refineries spread. Tobacco companies made cigarettes on an industrial scale. Today, they sell 6.5 trillion cigarettes every year.Our bodies responded with defenses honed over hundreds of thousands of years. One of their most potent responses was inflammation. But instead of brief bursts of inflammation, many people began to experience it constantly.Many studies now suggest that chronic inflammation represents an important link between airborne toxins and disease. In the brain, for example, chronic inflammation may impair our ability to clear up defective proteins. As those proteins accumulate, they may lead to dementia.Pathogens can hitch a ride on particles of pollutants. When they get in our noses, they can make contact with nerve endings. There, they can trigger even more inflammation.“They provide this highway that’s a direct route to the brain,” Dr. Fox, of the University of California, Los Angeles, said. “I think that’s what makes this a particularly scary story.”Some genetic variants that arose in our smoky past may offer some help now. They might allow some people to live long despite smoking, Dr. Finch and Dr. Trumble suggest. But the researchers have studied another gene for which the opposite seems to be true: a variant that was once helpful has become harmful in an age of rising air pollution.The variant, ApoE4, first came to light because it drastically raises the risk of developing Alzheimer’s disease. More recently, researchers have also discovered that ApoE4 increases the risk that exposure to air pollution leads to dementia.But these studies were restricted to industrialized countries. When researchers looked to other societies — such as farmers in poor villages in Ghana, or indigenous forest-dwellers in Bolivia — ApoE4 had a very different effect.In these societies, infectious diseases remain a major cause of death, especially in children. Researchers have found that in such places, ApoE4 increases the odds that people will survive to adulthood and have children.Natural selection may have favored ApoE4 for hundreds of thousands of years because of this ability to increase survival. But this gene and others may have had harmful side effects that remained invisible until the sooty, smoky modern age.