BRAVE NEW EXPOSOME: How a Toxic Civilization Is Changing Our Genetics

Art direction: huxley.media via OpenAI Images

For a long time, scientists believed that human longevity and health were determined primarily by genetics and secondarily by lifestyle. Over time, the picture became more complex. Genes are merely a “loaded gun”. But who pulls the trigger? It turns out that the environment does — the very environment that our civilization has been transforming for millennia. We alter the climate and landscape, destroy forests and species, and poison water and air. Humanity has reached a point beyond which genetic determinism can no longer serve as a smokescreen absolving us of responsibility for caring for the environment in which we live.

THE CHEMICAL COCKTAIL AND BIOLOGICAL CITIZENSHIP

ompared with our distant ancestors, we live more comfortably and longer, have overcome the epidemics of the past, and have learned to treat many diseases that were once considered incurable. Yet despite these achievements, the 21st century has witnessed an explosive rise in chronic diseases, mental disorders, and infertility. Problems associated with DNA mutations are accumulating so rapidly that science is struggling to keep pace. To make sense of what is happening, scientists coined a term: the exposome. In 2005, epidemiologist Christopher Wild introduced it into scientific discourse. DNA still largely determines our health and longevity, but the exposome — the totality of environmental exposures and the body’s responses to them — plays an equally important role. Modern urban dwellers come into contact every day with numerous synthetic compounds that simply did not exist in the environment of their pre-industrial ancestors. Thus, in the 21st century, human identity is defined not only by ethnic or linguistic affiliation. Of greater existential significance is the “biological passport” — the human body’s ability to cope with external environmental factors.

Modern exposome science is moving increasingly away from studying the isolated effects of individual substances. Reality is a continuous, complex “chemical cocktail” whose components can interact with one another, in some cases amplifying each other’s biological effects. The exposome is a multilevel system consisting of three layers. The outer layer encompasses factors on a planetary and urban scale: climate shifts, temperature anomalies, and background radiation. Within this layer, air pollution in megacities caused by fine particles of dust, soot, and heavy metals is recognized as the most destructive factor. Penetrating the pulmonary barrier and entering the bloodstream, these particles trigger immune-mediated inflammation, strokes, and heart attacks. The second layer is the microenvironment of our “chemical everyday life”: food containing agricultural chemical residues, growth hormones in meat, plastics, stretch films, water-repellent coatings, tin cans, household chemicals, and cosmetics. Finally, the third layer is the internal exposome — the body’s response to toxic stress that damages DNA and the microbiome. Today, this stress is global in nature because there are no longer any places on the planet completely free from exposome-related exposures. For example, traces of microplastic deposition can be found even in geographically isolated ecosystems such as Iceland, New Zealand, and the mountainous regions of Albania.

CHRONICLES OF ANCIENT POISONINGS

But you are mistaken if you think that “things were better in the past”. The modern exposome crisis is already the fifth of its kind. With each new technological leap, humanity radically altered the composition of the air, water, and food. The first was the “cave crisis”, which occurred roughly between 1.5 million and 400,000 years ago. When humans began using fire inside their dwellings, toxic combustion products triggered a wave of pulmonary diseases. Exposure to combustion products over hundreds of thousands of years may have been one of the factors driving natural selection in systems responsible for xenobiotic metabolism. Next, approximately 10,000–12,000 years ago, came the Neolithic transition to agriculture and animal husbandry. Sedentary lifestyles, increasing population density, and close contact with domesticated animals created conditions for the spread of zoonotic diseases and the emergence of new human infections. As cereals became a staple, the diets of agricultural societies grew less diverse, while the number of copies of the amylase gene AMY1 increased. This adaptation was necessary to break down complex plant carbohydrates more efficiently. Transcontinental trade networks carried not only cultural artifacts but also pathogens that reshaped the exposome of settled communities.

The gut microbiome lost ancient bacterial strains characteristic of hunter-gatherers. Micronutrient deficiencies caused bones to become thinner, average height declined, and the first pandemic of dental caries in history began. Apparently, it was also during this period that humans first encountered the toxic fungus ergot. The earliest written reference to “growths on grain” appears on Assyrian clay tablets dating to 600 BCE. The third exposome crisis is associated with the history of Ancient Rome, which developed a metallurgical industry on an enormous scale, creating a global background of inorganic heavy-metal contamination. The reason was that lead became a cornerstone of everyday Roman life, used to manufacture water pipes, cosmetics, and tableware. Analysis of human remains discovered in Pompeii revealed lead levels many times higher than natural background concentrations! The Romans had no idea that grape juice boiled down in lead vessels could turn into poison. The juice was reduced to a thick syrup called sapa, which was used to sweeten wine. When prepared in lead cookware, the acids in grape juice caused lead to leach into the syrup. This sweet poison devastated the elite in particular, causing infertility, miscarriages, and gout. A hypothesis later emerged linking the eccentric behavior of Emperors Caligula and Nero to lead poisoning, although proving it two thousand years later is impossible.

“TAMING” TOXINS

In those days, beauty, prestige, and status could be deadly. By using antimony sulfide as eyeliner, aristocratic women rubbed a neurotoxin into their mucous membranes. The resulting pallor and mysterious gleam in their eyes were considered the ideal of beauty. People tried to “tame” toxins in various ways. Thus, King Mithridates VI Eupator of Pontus developed a phenomenal tolerance to poisons by taking daily microdoses of every poison known to him. After suffering defeat at the hands of the Romans, he unsuccessfully attempted to poison himself. In the end, he had to ask his bodyguard to run him through with a sword. According to historical hypotheses, toxins played an enormous role in ancient cults. At Delphi, attempts were made to explain the state of the Pythian priestesses through exposure to gases rising from geological faults; ethylene was among the substances proposed. According to one well-known theory, the psychoactive effects of kykeon, used in the Eleusinian Mysteries, may have been linked to ergot alkaloids — chemical relatives of the compounds from which LSD was created many centuries later. Plato, Cicero, and Marcus Aurelius were initiated into the Eleusinian Mysteries. During the Middle Ages, the recipe for this “ancient LSD” was lost, while ergot became the cause of epidemics of ergotism. In 944 CE, it claimed thousands of lives in France. In the early modern period, convulsive ergotism caused by this fungus was mistaken for demonic possession. There is even a well-known hypothesis, although disputed by historians, that the strange behavior of the Salem girls in 1692 may have been linked to convulsive ergotism.

INDUSTRIAL APOCALYPSE

Victorian smog became the symbol of the fourth exposome crisis. From the mid-19th to the early 20th century, the rapid growth of factories filled the air with a deadly mixture of dust, sulfur dioxide, and soot. Londoners went months without seeing the sun, and children suffered from rickets due to vitamin D deficiency. In the most disadvantaged industrial cities and working-class neighborhoods, life expectancy during certain periods of the 19th century could fall by approximately 20–30 years, largely because of extremely high infant mortality, infectious diseases, unsanitary conditions, and air pollution. Another symbol was “Scheele’s Green”, a pigment based on inorganic arsenic. It was used in fashionable wallpapers, textiles, and toys. In damp rooms, microorganisms could transform arsenic compounds from these pigments into volatile organoarsenic compounds. In the 19th century, arsenic-containing wallpaper became the subject of heated medical and public debate: doctors detected concentrations of arsenic that would today be considered entirely unacceptable in residential interiors.

However, humanity did not immediately come to understand that poisons do not simply disappear but accumulate in tissues. In 1814, the French chemist Mathieu Orfila was the first to make this claim in his Treatise on Poisons. In 1840, he succeeded in extracting arsenic from exhumed tissues. Later, another French scientist, the physiologist Claude Bernard, revealed the mechanisms by which poisons act at the cellular level. Yet humanity was still far from realizing that civilization was slowly poisoning both the planet and itself. That realization came only in 1962, when biologist Rachel Carson published her manifesto Silent Spring, devoted to the bioaccumulation of the insecticide DDT in the food chain. The book became one of the most important catalysts of the modern environmental movement and helped shape the political climate in which the US Environmental Protection Agency was established in 1970.

THE AGE OF CATASTROPHES

The 20th century brought ecotoxicologists many unpleasant surprises. Three disasters, perhaps, became particularly notorious. In the Japanese city of Minamata, the Chisso chemical plant discharged mercury into the bay for years. Bacteria on the seabed converted it into methylmercury, which gradually poisoned everyone in the surrounding area. The local cats were the first to go mad. They committed suicide by throwing themselves into the sea. Then severe neurological damage began to emerge in humans. In 1976, the Italian ICMESA plant concealed the release of dioxin (TCDD) into the atmosphere of the town of Seveso, exposing hundreds of people to its effects. Later studies revealed an unusually high proportion of daughters among the offspring of men with high TCDD exposure (the mechanism behind this effect remains incompletely understood). The tragedy prompted Europe to adopt the Seveso Directive in 1982, requiring businesses to openly disclose risks. Today, it regulates safety at more than 11,000 facilities. In 1984, a pesticide manufacturer in Bhopal, India, decided to cut costs on its safety systems. The disaster claimed the lives of several tens of thousands of people, while the total number of those affected exceeded half a million. The Bhopal disaster provided a powerful impetus for tightening India’s environmental legislation, and shortly afterward, the Supreme Court of India, in M. C. Mehta v. Union of India, formulated the doctrine of absolute liability — the absolute liability of enterprises engaged in particularly hazardous activities.

BEWARE OF FISH!

Exposome crises have repeatedly reshaped the human diet. The world’s oceans have gradually turned into a chemical soup, and fish have become a food associated with an increased risk of neurotoxicity. Today, experts classify seafood according to its methylmercury content. The highest risk is associated with large, long-lived predators that accumulate methylmercury over many years — sharks, swordfish, marlin, and king mackerel. Their consumption should be reduced to a minimum, while bigeye tuna should be avoided altogether. It hunts in the deep layers of the ocean, where bottom-dwelling bacteria rapidly convert inorganic mercury into methylmercury. Medium-risk species include regular tuna, wild sea bass, gilthead sea bream, and large freshwater carp. The lowest risk is associated with small, fast-growing, non-predatory fish.

Mackerel, salmon, freshwater trout, herring, sardines, anchovies, hake, cod, pollock, shrimp, squid, mussels, scallops, and crabs do not have enough time to accumulate dangerous concentrations of mercury. At the molecular level, methylmercury binds tightly to proteins, so choosing the right fish is the only way to protect yourself. Cooking will not help. Interestingly, in the tissues of many marine animals, mercury coexists with high concentrations of selenium. Selenium can interact with mercury and modify its toxicity, although it cannot yet be regarded as a universal “antidote,” nor can the simple selenium-to-mercury ratio be used as an indicator of food safety. But why have mammals not developed a defense mechanism against heavy metals over the course of evolution? The answer lies in molecular mimicry. Heavy metal ions disguise themselves as beneficial trace elements and bind tightly to proteins.

THE CHEMICAL DECEPTION OF CELLS

Some heavy metals can remain in the body for years or even decades: lead, for example, can persist in bone tissue for an exceptionally long time. The body readily mistakes lead for calcium, incorporating it into the crystal lattice of bones and teeth. During bone fractures or pregnancy, lead begins to be released from the bones back into the bloodstream, causing acute secondary poisoning, anemia, and kidney damage. In 2010, more than 400 children died in Zamfara, Nigeria, poisoned by lead dust generated during artisanal gold mining. Cadmium, meanwhile, is particularly adept at mimicking zinc. It enters the bodies of residents of megacities through coal combustion, vehicle exhaust emissions, and tire wear, causing kidney failure, hypertension, and the deterioration of bone tissue. When Japanese mining companies discharged cadmium-contaminated wastewater into rice fields, the bones of people who ate rice grown there became so fragile that they could fracture from an ordinary cough.

No less terrifying is thallium, which paralyzes the nervous system. In 1996, the case of Robert Curley, whose wife poisoned him with thallium to collect life insurance money, attracted widespread attention. That same year, chemist Karen Wetterhahn became a victim of dimethylmercury. When two accidental drops landed on the back of her protective gloves, they penetrated the latex within 15 seconds. Five months later, Karen developed severe neurotoxic symptoms. She lost the ability to speak, became blind, and died shortly afterward. Such accidents are horrifying. But there were times when civilization deliberately saturated the medical exposome with mercury and antimony. Until the 20th century, calomel (mercury chloride) was prescribed to teething infants, while antimony was used to treat “thick blood” and inflammation. Such misconceptions even rewrote the biographies of geniuses. As is well known, Mozart did not die at the hands of Salieri in 1791. According to one medical hypothesis, his condition may have been worsened by calomel and antimony-based “tartar emetic”, both used in medicine at the time. However, the exact cause of the genius’s death remains a subject of debate. It is possible that Napoleon Bonaparte’s life ended in a similar way. Excessive “therapeutic” doses of antimony and calomel could well have caused an irreversible electrolyte imbalance and cardiac arrest.

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PLASTIC CIVILIZATION AND THE NANO-KILLER

Unlike heavy metals, plastic began its deadly career relatively recently. “Plastic civilization” began in 1862, when Alexander Parkes demonstrated Parkesine, an artificial plastic made from cellulose. But it was not until the 20th century that this material acquired its deadly power. Today, the PlastChem database lists more than 16,000 chemicals associated with the production and use of plastics. At least 4,200 of them are classified as chemicals of concern due to their toxicity, persistence, potential for bioaccumulation, or high mobility. Potentially hazardous chemical components can be found in many different types of plastic. Polyvinyl chloride may contain phthalates, which pose a threat to the hormonal system when packaging is heated. Phthalates enter the body not only through food but also through the skin, as they are used as fragrance fixatives in perfumes, deodorants, and shampoos. Potentially problematic chemical components may also be present in polystyrene, which is used, among other things, to manufacture disposable tableware and containers.

Equally dangerous is bisphenol A, whose use in food-contact materials was banned by the European Union in December 2024, with transitional periods provided for certain products. However, it is still found in the thermal paper used for cash register receipts, from which it can transfer to the skin and increase the body’s overall exposure. Polyethylene terephthalate is widely used to manufacture bottles for water and oil, while polyethylene is used for reusable containers, flexible bags, food wrap, and milk bottles. The threat comes not from plastic itself but from its nanoparticles, which can pass through the membranes of intestinal cells directly into the bloodstream and cause persistent, low-grade inflammation in tissues.

In water, nanoparticles act like electrostatic sponges: they absorb pesticides, heavy metals, and dioxins from the surrounding environment and carry them into cells. The latest tests show that nanoplastic particles in the ocean become coated with a so-called “plastisphere biofilm”. The plastisphere can create favorable conditions for the accumulation of microorganisms and the exchange of antibiotic resistance genes, which is why microplastics are also considered potential carriers of antibiotic resistance.

REPRODUCTIVE NOSEDIVE AND THE LONGEVITY PARADOX

We are witnessing a reproductive nosedive across civilization. To maintain population replacement, the total fertility rate must average 2.1 children per woman. However, in more than two-thirds of the world’s 195 countries, it has fallen below this threshold, a trend observed in both wealthy and developing nations. Alongside powerful social and economic factors, researchers are also investigating the possible contribution of deteriorating reproductive health. Over the past 50 years, the average sperm concentration among men worldwide has declined by more than 50%. Is it a coincidence that this phenomenon has coincided with the mass production of materials that do not exist in nature? How well do we understand their effects on biological systems? Consider, for example, endocrine-disrupting chemicals (EDCs). They can mimic natural hormones, block their receptors, or alter hormone synthesis, transport, metabolism, and elimination. Scientists have linked EDCs to a reduction in anogenital distance in newborn boys — a marker that several studies have associated with prenatal exposure to phthalates.

Pathological changes during embryonic development can subsequently affect male fertility in adulthood. In women, the same chemical environment has been linked to the widespread prevalence of endometriosis, polycystic ovary syndrome, and premature depletion of ovarian reserves. If the observed trends in the deterioration of certain reproductive health indicators continue, the burden on reproductive medicine could increase significantly during the 21st century. Equally paradoxical developments are occurring in life expectancy. Life expectancy has now risen to 73.3 years, but healthy life expectancy remains stuck at 62.8 years. This critical gap of 10–11 years means that people spend their final decade in far from optimal health. Noncommunicable chronic diseases now account for 74% of all deaths worldwide. Mortality from dementia and Alzheimer’s disease has tripled over the past 20 years, making it the fifth leading cause of death globally.

AN EVOLUTIONARY DEAD END

Will we ever be able to adapt to heavy metals and plastics through evolution? The question is far from simple. The human internal exposome is a dynamic environment in which trillions of gut bacteria act as a buffer between external chemicals and our cells. Under the pressures of civilization, this buffer has been eroding for thousands of years. Modern urban dwellers have lost up to 40% of their ancestral bacterial species. In addition, under the influence of psychosocial stress, the hypothalamic–pituitary–adrenal axis (HPA axis) of megacity residents produces excessive amounts of cortisol. When this hormone reaches the gut, it alters bacterial behavior: their level of integration decreases, disrupting the tight junctions of the intestinal epithelium. There is no evidence to suggest that we will “adapt to everything”. An evolutionary dead end cannot be avoided for four reasons.

First, the genetic fixation of a new mutation requires thousands of years, while thousands of new compounds are synthesized every year. Second, natural selection eliminates only those organisms that die before passing their genes on to their offspring. Yet modern toxins cause cancer, strokes, and Alzheimer’s disease after the reproductive cycle has ended. The third reason is that medical technologies alter selective pressure and, in some cases, weaken the effects of natural selection. Finally, the fourth reason is that endocrine disruptors cause infertility not only among the less adapted but throughout the entire population. Nevertheless, one case of remarkable adaptation is known. In the Argentine town of San Antonio de los Cobres, groundwater contains arsenic at concentrations 20 times higher than the permissible limit. However, the local population carries genetic variants in liver cells associated with more efficient arsenic metabolism. Genetic studies have identified signs of positive natural selection here — a rare example of a population adapting to exposure to a natural toxin.

THE BIOLOGICAL CURSE OF GENERATIONS

Another problem is epigenetic memory. External influences can alter gene activity without changing the DNA sequence itself. In humans, epigenetic inheritance remains a subject of scientific debate. However, experiments on animals have documented such changes and their associated phenotypic effects. A famous experiment with mice showed that when the smell of acetophenone was paired with an electric shock, the animals’ offspring exhibited increased sensitivity to the same smell, even though they had never experienced electric shocks themselves. By spraying insecticides on a massive scale and introducing chemicals without adequate testing, humanity was essentially taking out a toxicological loan from the future. The generations of the 21st century are now paying it back. Sociocultural catastrophes such as the Holocaust and the Dutch Hunger Winter are known to leave a metabolic imprint. Descendants of survivors inherit an altered HPA axis, even when raised in favorable environments. Similar mechanisms operate in epigenetic toxicology. In experiments on rats, exposure of pregnant females to DDT was associated with changes detectable even in the third generation of offspring, which had never been directly exposed to the pesticide. In one experimental lineage, obesity developed in 75% of third-generation males. Researchers also identified an increased incidence of certain other disorders and changes in sperm DNA methylation. In other words, the chemical environment created in the mid-20th century continues to exert biological control over human health today.

DESIGNING CITIES FOR LONGEVITY

Recognizing that humans cannot adapt naturally to a rapidly changing chemical environment quickly enough, scientists are searching for ways to artificially strengthen the body’s defense mechanisms. Researchers can learn a great deal from insects and bacteria evolving in waste dumps. For example, insect pests develop resistance to new poisons within just three years of their introduction. Meanwhile, the bacterium Ideonella sakaiensis, discovered at a Japanese waste recycling facility, uses enzymes that break down polyethylene terephthalate into its original components. Genetic engineering has also achieved some success. CRISPR-Cas9 technology and the use of lipid nanoparticles already make it possible to modify the activity of certain genes. However, their application specifically for “detoxification” from plastics and heavy metals remains an experimental prospect. Therefore, the main emphasis is on abandoning the linear logic of the industrial model: “raw materials — production — purchase — use — waste”. As an alternative, the concept of Design for Longevity is proposed — circular design and a circular economy. The city is viewed as a protective shell for human biology rather than an aggressive environment that destroys it.

New urban development programs are putting forward numerous groundbreaking ideas, such as bioadaptive facades. Water circulates inside such facades together with microalgae, which absorb carbon dioxide and fine particulate matter much more efficiently than urban trees. By capturing heavy metals from smog, the algae become biomass that can subsequently be used to produce biofuel. Another model is the “sponge city”. The idea is to prevent water carrying lead and cadmium dust from washing into rivers, allowing it instead to be absorbed locally by porous concrete, specialized substrates, and plant root systems. Innovative urban greening also involves creating living walls of “supertrees” — megastructures that generate controlled microclimates.

Using bioluminescent plants and bacteria, urban planners hope to eliminate “light pollution” while preserving melatonin production. And although some of these ideas may seem fantastical, there is already evidence that humans can control the exposome. The global phaseout of tetraethyllead in automotive fuel, completed by 2021, can be considered a historic triumph. Following this, blood lead levels worldwide declined significantly. Cleaner air prevented millions of premature strokes and restored several points to the population’s average IQ.

A PERSONAL DETOX MANIFESTO

The programs discussed above will require considerable effort and time. However, you can begin reducing your toxic exposure at home right now. For example, installing a water purification system with a reverse osmosis membrane is an excellent way to filter out fluoride, arsenic, trihalomethanes, and nanoplastics. Avoid buying water in single-use PET plastic bottles. Switch to glass or stainless steel bottles. Stop using plastic tableware for hot foods, and do not heat plastic containers in the microwave. Replace plastic cutting boards with wooden or stone alternatives. Dispose of frying pans with damaged Teflon coatings and replace them with cast iron, stainless steel, or pure ceramic cookware.

To minimize mercury exposure, prioritize small, fast-growing fish. Soak vegetables and leafy greens for 15 minutes in water with added baking soda to reduce surface pesticide residues. Clean regularly with a damp cloth, as phthalates, flame retardants, and microplastics accumulate in household dust. Install air purifiers with HEPA filters in your rooms to capture harmful particles. Use natural cosmetics. Avoid cheap particleboard furniture, varnishes, and paints that emit formaldehyde. At the individual, global, and urban levels, we can still escape the trap of “hypertechnological alienation”. To do so, in the existential conflict between technological progress and the physiological limits of living cells, we will have to choose the side of life.