Above about five thousand metres, the air thins to the point where ordinary human physiology begins to fail. Oxygen pressure falls, breathing deepens, and the body's cells adjust in ways that, if given time, allow people to live and work in such conditions for extended periods. The study of these adjustments has a long history, going back to early experiments with sealed chambers in the nineteenth century, and it has been intensified by the increasing popularity of high-altitude trekking and mountaineering.

The problem is not lack of oxygen in the atmosphere - the proportion of oxygen in air remains the same at all altitudes - but lower air pressure. At the summit of Everest, around 8,850 metres, the pressure is roughly a third of that at sea level, so each breath delivers about a third as much oxygen to the lungs. A climber arriving at altitude from sea level without acclimatisation feels the effect within hours: headache, fatigue, nausea, difficulty sleeping. These symptoms, known collectively as acute mountain sickness, affect a substantial fraction of visitors to altitudes above three thousand metres.

Acclimatisation proceeds through several stages. Within hours, the body increases its breathing rate and heart rate to deliver more oxygen despite the lower pressure. Within days, the kidneys begin to excrete more bicarbonate, reducing the alkalinity that increased breathing would otherwise produce. Over weeks, the bone marrow produces more red blood cells, raising the oxygen-carrying capacity of the blood. And over months and years, small blood vessels proliferate in the tissues, shortening the distance oxygen has to diffuse. Each of these stages has limits; beyond about eight thousand metres, no amount of acclimatisation prevents gradual deterioration, and climbers at such altitudes lose weight, muscle mass and cognitive function even when well fed.

Some populations have adapted to high altitude over much longer periods. Tibetan and Andean peoples, who have lived for thousands of years above three thousand metres, differ from sea-level visitors in several physiological respects. Tibetans tend to have lower haemoglobin levels than Andeans despite living at similar altitudes, but they breathe more deeply and show higher blood flow to the brain. Physiologist Dr. Kalden Dorjee, working at the University of Lhasa, has argued that these two patterns represent different evolutionary solutions to the same problem, selected under different ecological conditions. Recent genetic studies have identified variants of the gene EPAS1 in Tibetans that are otherwise rare in global populations, and that appear to have been inherited from Denisovans, a now-extinct relative of modern humans.

For ordinary climbers, the practical implications concern pace. Expeditions to the highest summits typically involve a scheme of 'climb high, sleep low', in which climbers ascend to a higher camp during the day and descend to a lower one to sleep, allowing red-cell production and other slow adaptations to catch up. Attempts to rush the process, particularly when supported by the use of supplemental oxygen, can produce dangerous illnesses. Two of these are well defined. High-altitude pulmonary oedema (HAPE) involves the accumulation of fluid in the lungs; high-altitude cerebral oedema (HACE) involves swelling of the brain. Both are life-threatening, and immediate descent is usually the only reliable treatment.

Supplemental oxygen reduces but does not eliminate these risks. A climber breathing bottled oxygen at 8,000 metres is experiencing something closer to the physiology of sea level at perhaps 5,500 metres, which is still challenging. Many modern expeditions also use a hyperbaric bag - a sealed chamber that can be pressurised with a foot pump - to treat early symptoms of HAPE or HACE while a descent is arranged.

Dr. Dorjee warns that the social side of altitude illness deserves more attention. On commercial expeditions, climbers may hesitate to admit symptoms for fear of losing a place in the group or a substantial financial investment. Group dynamics can push individuals beyond what their physiology will allow. Some recent expedition guidelines explicitly require that climbers reporting symptoms be turned back without argument, and that blame or financial penalty not attach to such decisions. Whether or not these guidelines are followed in practice is a separate question, and one that the expanding commercial climbing industry will continue to face.