The Long Path to Understanding Air

Before the 18th century, air was seen as a single, indivisible substance essential for life. Ancient Greek philosophers like Empedocles and Aristotle had included air among the four fundamental elements. This view persisted for nearly two thousand years, with scholars regarding the atmosphere as a simple carrier of the vital force that sustained both flame and living beings. The true nature of air began to emerge only when natural philosophers started to measure its properties and isolate its components.

Jan Baptist van Helmont, a 17th‑century Flemish physician and alchemist, was among the first to distinguish between different kinds of air‑like substances, which he called “gases” derived from “chaos.” He observed that burning charcoal and fermenting wine both produced a heavy, invisible substance that could extinguish a flame. Robert Boyle and his contemporaries further demonstrated that air was not a passive entity; they showed that it was necessary for combustion and for the life of animals, but they lacked the conceptual framework to break air into its separate components. The concept of elemental gases was still decades away.

The Phlogiston Theory and the Puzzle of Combustion

The dominant chemical theory of the 17th and 18th centuries was phlogiston, developed by German chemists Johann Joachim Becher and Georg Ernst Stahl. According to this theory, all flammable materials contained a universal “principle of fire”—phlogiston—that was released during burning. A candle lost its phlogiston to the surrounding air, leaving behind a smaller amount of ash. When air became saturated with phlogiston, combustion ceased. Respiration was explained in similar terms: living bodies exhaled phlogiston, purifying the air and keeping them alive.

By the mid‑1700s, the phlogiston model was under strain. Experimenters noticed that some metals gained weight when heated in air, a fact that contradicted the idea of losing a weightless phlogiston. The air left after combustion could no longer support flame or life, but no one had yet identified what was being removed from it. The stage was set for a series of brilliant, nearly simultaneous discoveries that would overturn the entire edifice of 18th‑century chemistry.

The Discovery of Oxygen: Three Scientists, One Element

Joseph Priestley and Dephlogisticated Air

On 1 August 1774, the English clergyman and amateur scientist Joseph Priestley used a large burning lens to focus sunlight onto a sample of mercuric oxide (red calx of mercury) inside a closed glass vessel. He observed that the substance quickly decomposed, releasing a gas that he collected over water. This gas astonished him: a candle burned in it with a remarkably vigorous flame, and a mouse placed in a closed container of the gas survived far longer than in ordinary air. In his subsequent writings, Priestley famously inhaled the gas himself and felt a “light and easy sensation” in his chest. He called the new substance “dephlogisticated air,” believing it was ordinary atmospheric air stripped of its phlogiston—hence its ability to absorb more phlogiston from burning materials and living creatures.

Priestley was a devout follower of the phlogiston theory and never fully abandoned it, even when his own discovery helped to dismantle it. Nevertheless, his experiments with dephlogisticated air provided the first clear description of what we now call oxygen and demonstrated its role in sustaining life and flame.

Carl Wilhelm Scheele’s Fire Air

Unbeknownst to Priestley, the Swedish apothecary and chemist Carl Wilhelm Scheele had already produced oxygen at least two years earlier, around 1772. Scheele heated a variety of substances—saltpetre (potassium nitrate), magnesium nitrate, and others—and collected a gas that he termed “fire air” because it supported combustion so vigorously. He observed that the atmosphere was composed of fire air and a second, non‑reactive component he called “foul air” (now known to be nitrogen). His careful notes detailed many of the same properties Priestley would later report.

Scheele, however, delayed the publication of his work. His book Chemische Abhandlung von der Luft und dem Feuer (Chemical Treatise on Air and Fire) did not appear in print until 1777, by which time the chemical world’s attention had already been captured by someone else entirely. Scheele’s contributions are now recognized as independent and pioneering, even if his lagging publication muted his immediate influence.

Antoine Lavoisier and the Chemical Revolution

The French tax administrator and virtuoso chemist Antoine Lavoisier heard of Priestley’s findings during a visit to Paris in October 1774. He immediately grasped the deeper implications. Lavoisier repeated Priestley’s experiments with meticulous gravimetric control, weighing all reactants and products in sealed vessels. He demonstrated that when phosphorus or mercury was burned in a limited amount of air, the weight of the remaining solid and the absorbed part of the air exactly matched the weight lost from the air. The process was not the loss of phlogiston, but the combination of the burning material with a specific fraction of the atmosphere.

By 1777, Lavoisier had firmly identified this fraction as a distinct chemical element that he named oxygène, from the Greek roots meaning “acid‑former.” He believed—correctly, for many cases—that oxygen was the principle behind all acids, a notion later revised but powerfully unifying at the time. In his Traité Élémentaire de Chimie (1789), Lavoisier presented a new oxygen‑centered theory of combustion, calcination, and respiration that swept away the phlogiston model and inaugurated modern chemistry.

From Combustion to Respiration: Lavoisier’s Dual Insight

Lavoisier did not stop at combustion. He immediately extended the same logic to the functioning of the animal body. With the mathematician Pierre‑Simon Laplace, he constructed an ice‑walled calorimeter in the 1780s that allowed them to measure the heat produced by a guinea pig and compare it directly with the heat released by burning a known amount of carbon. They showed that respiration was, in essence, a slow, controlled combustion of carbon and hydrogen carried out in the lungs, with oxygen gas inhaled and transformed into exhaled carbon dioxide and water vapour. In their words, “respiration is a combustion, slow indeed, but otherwise perfectly similar to that of charcoal.”

This discovery fundamentally reoriented physiology. Life could now be studied as a chemical process, not a mysterious vital force. The lungs were no longer seen merely as cooling organs or bellows, but as the primary site where blood took up oxygen from the air and released the products of metabolic combustion. Lavoisier’s work established the basis for understanding energy metabolism—a scientific thread that would eventually lead to the calorie, the basal metabolic rate, and modern nutrition science.

Oxygen Transport and the Emerging Physiology of Respiration

Once oxygen’s role was clear, new questions emerged. How did the body carry this essential gas from the lungs to the deepest tissues? Early 19th‑century physiologists first suspected that oxygen simply dissolved in the blood serum. However, by the 1860s, detailed gas‑analysis studies by scientists such as Felix Hoppe‑Seyler had demonstrated that blood could hold far more oxygen than physical solubility alone permitted. The search for the responsible agent intensified.

In 1864, the German chemist Ernst Felix Hoppe‑Seyler (the same Hoppe‑Seyler) crystallized a red protein from blood and called it haemoglobin. Later research revealed that haemoglobin contains iron‑containing heme groups that bind oxygen reversibly—a property that allows the protein to load oxygen in the lungs and unload it precisely where metabolism is most active. This elegant mechanism explained the bright red colour of oxygenated arterial blood and the darker, bluish hue of venous blood returning to the heart.

Subsequent discoveries unfolded rapidly: the sigmoid oxygen‑binding curve, the Bohr effect describing how increased carbon dioxide and acidity promote oxygen release, and the role of 2,3‑bisphosphoglycerate in fine‑tuning haemoglobin’s affinity. These findings crystallised the concept of an internal respiratory system in which the blood, heart, and lungs work as an integrated delivery network—an understanding that directly supports modern critical care, anaesthesia, and the treatment of lung diseases.

Cellular Respiration: The Inner Fire of the Cell

The combustion model proposed by Lavoisier was correct in outline but wrong in location. Throughout the 19th century, respiration was widely thought to occur in the lungs or the bloodstream, where oxygen was believed to “burn” carbon‑bearing substrates. The true theatre of respiration shifted in the early 20th century, when biochemists turned their attention to the minute structures inside cells.

In the 1920s and 1930s, Otto Warburg and later Hans Krebs sketched the intricate pathways by which cells extract energy from nutrients. The Krebs cycle (or citric acid cycle), elucidated by Krebs in 1937, was found to be the central hub where breakdown products of carbohydrates, fats, and proteins are oxidised to carbon dioxide, with the simultaneous production of energy‑rich electron carriers. The final step—the one that requires molecular oxygen—was shown to take place on the inner membrane of mitochondria, through the electron transport chain. Here, oxygen acts as the terminal electron acceptor, pulling electrons through a series of protein complexes to form water and, in the process, driving the synthesis of adenosine triphosphate (ATP), the energy currency of the cell.

This understanding transformed biology. The mitochondria, often described as the powerhouses of the cell, are essentially microscopic engines that carry out a tightly regulated version of the combustion Lavoisier described. The oxygen we inhale today reaches those minute structures billions of times over, sustaining every thought, movement, and heartbeat. Cellular respiration now forms a central pillar of biochemistry education and medical research, linking the elemental gas discovered in the 1770s directly to the molecular choreography of life.

Clinical and Medical Legacies of Oxygen Discovery

The identification of oxygen soon spilled over from pure science into practical medicine. By the late 18th and early 19th centuries, practitioners began experimenting with oxygen inhalation for a variety of ailments, from asthma to consumption. Thomas Beddoes opened the Pneumatic Institution in Bristol in 1799, where oxygen and other gases were administered to patients, foreshadowing modern respiratory therapy.

Real‑world applications accelerated after the recognition that many diseases cause tissue hypoxia. Oxygen therapy became a cornerstone of hospital care, from the simple nasal cannula to mechanical ventilators in intensive care units. Anaesthesiology, which relies on precise mixtures of oxygen and other gases, grew directly out of the chemical revolution Lavoisier helped launch. Hyperbaric oxygen therapy—exposing patients to high‑pressure oxygen—now treats decompression sickness, carbon monoxide poisoning, and chronic wounds by boosting the amount of dissolved oxygen in the plasma and tissues.

Moreover, the discovery of oxygen’s role in respiration gave birth to entire fields: exercise physiology, high‑altitude medicine, and the study of reactive oxygen species. Scientists understand that while oxygen is essential for ATP production, its partially reduced forms—free radicals—can damage DNA, proteins, and lipids. This dual nature of oxygen is now a central theme in ageing research, neuroprotection, and the development of antioxidant therapies. The World Health Organization’s inclusion of oxygen on the List of Essential Medicines underscores its enduring importance for modern health systems.

The Scientific Mindset That Changed Respiration Forever

The story of oxygen’s discovery is not just a chronicle of a single element; it is a narrative about how a new way of thinking—quantitative, sceptical of inherited dogma, and relentlessly experimental—can reshape an entire science. Priestley, Scheele, and Lavoisier each approached the same mystery from different angles, and their combined work eliminated the phlogiston theory and supplanted it with the oxygen‑based chemistry we still use today.

When Lavoisier declared that “nothing is lost, nothing is created, everything is transformed,” he was laying the intellectual foundation for the principle of conservation of mass, and simultaneously for a physiology in which the body’s heat and motion are the balanced outcome of chemical exchanges with the environment. The discovery of oxygen thus linked the inanimate world of mineral combustion with the animate world of breath and metabolism, bridging physics, chemistry, and biology in a single elegant framework.

From Priestley’s mercuric oxide on a summer day to modern mitochondriologists mapping the electron transport chain, the path of oxygen discovery has been one of continual refinement and deepening insight. The breath we draw connects us to that 18th‑century moment—a moment when a handful of curious individuals learned to read the atmosphere’s hidden language and, in doing so, illuminated the inner workings of life itself.

The Enduring Frontier of Oxygen Research

Even after more than two centuries, oxygen continues to challenge researchers. The fields of neuroenergetics, cancer metabolism (the Warburg effect), and stem cell biology all turn on how cells sense and respond to oxygen availability. The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability, a molecular pathway that coordinates the expression of hundreds of genes in response to hypoxia. Their work builds directly on the foundation laid by the early gas chemists, showing that the story of oxygen is far from over.

What began as a curious gas in a sealed vessel has become one of the most thoroughly studied molecules in human history. Its discovery not only explained why a candle burns brightly in a newly made gas but also why we must breathe—and continues to shape the way we treat disease, understand ageing, and explore the boundaries of life in extreme environments.