High Altitude Medicine : A Brief History

George W. Rodway

As far back as 300 BC, Aristotle (384-322 BC) may have been aware that air was ‘too thin for respiration’ on mountain peaks.1 Shortly afterwards, Xenophon and Alexander the Great’s military expeditions crossed Central Asia, where they were thought to have reached altitudes in the vicinity of 4500 m in Afghanistan. These very early explorers did not, unfortunately, leave detailed descriptions of the physical symptoms and signs they encountered when at high altitude. In the classical Chinese history, the Ch’ien Han Shu (dating from about 30 BC), Chinese travellers near present-day Kashmir labelled an area with a name that was subsequently translated as ‘Headache Mountains’. In about 35 BC, Too Kin (a high official of the Western Pan Dynasty) described crossing into Kashmir over ranges he called the Big and Little Headache Mountains. Some 400 years later, a more explicit description of mountain sickness comes from a Buddhist missionary, Fa-Hsien (334-420 AD), who was crossing a pass some 3600 – 4200 m high in the Little Snowy Mountains of China (c. 400 AD)…Hwey-Ring, one of Fa-Hsien’s fellow-travellers, could not go any farther.2

A white froth came from his mouth and he said to Fa-Hsien, “I cannot live any longer. Do immediately go away, that we do not all die here…”

Could this be the first written description of someone dying of what we now recognize as high altitude pulmonary edema (HAPE)? In the 14th and 15th centuries, the Mongol Hordes swept across Central Asia, high Tibet, and into Europe. One of the Mongol chieftains, Mirza Muhammad Haider, wrote in 15443

The symptoms are a feeling of severe sickness…one’s breath so seizes him that he becomes exhausted, as if he had run up a steep hill with a heavy burden on his back. On account of the oppression it causes, it is difficult to sleep…the eyes are hardly closed before one is awake with start caused by the oppression of the lungs and chest…when overcome by this malady the patient becomes senseless and begins to talk nonsense, and sometimes the power of speech is lost. This malady only attacks strangers; the people of Tibet know nothing of it, nor do their doctors know why it attacks strangers.

Haider obviously had very keen powers of observation—he noted important signs and symptoms of mountain sickness, and recognized that permanent altitude residents were afforded significant protection from high altitude maladies. No such distinct mention of acclimatization has been found in documents previous to this period of time.2

Horace Benedict de Saussure

Horace Benedict de Saussure

Early theories of what prompted mountain sickness was, perhaps not surprisingly, rife with wild speculation. From earthly phenomena, such as the wind or cold, to spiritual or otherworldly things such as gods and dragons, there were as many etiological hypotheses as there were sufferers.4 Astute observations and graphic descriptions were useful to early physical and life scientists wrestling with this confusing issue of altitude and its influence on the human body. It took many years, however, for the pieces to start to fall into place, such that it was possible to have some fledgling, evidence-based understanding of what made some humans (but not others) very sick when they travelled to the high mountains.

Depiction of an early ascent of Mont Blanc

Depiction of an early ascent of Mont Blanc

In 1787, Horace Benedict de Saussure made the second ascent of Mont Blanc (4810 m), in the French Alps. This ascent of Mont Blanc prompted de Saussure to study pulse, respirations, temperature and symptoms in humans at high altitudes in the European Alps, during the years that followed. He included a Torricellian barometer in his mountain kit during his 1787 ascent. Saussure started to effectively join the pieces of the puzzle regarding his symptoms at altitude and the barometric pressure, and wrote :

The sort of weariness which proceeds from the rarity of the air is absolutely insurmountable; when it is at its height, the most imminent peril will not make you move a step faster…Since the air (on the summit of Mont Blanc) had hardly more than half of its usual density, compensation had to be made for the lack of density by the frequency of inspirations… That is the cause of the fatigue that one experiences at great heights. For while the respiration is accelerating, so also is the circulation.5

Priestley and Lavoisier’s discovery of oxygen in the 1770s may have had a strong influence on the great German explorer, Alexander von Humboldt, and his thoughts surrounding the relationship of oxygen to mountain sickness. In 1802, von Humboldt climbed to approximately 5730 m on Chimborazo in the Andes of Ecuador and made the suggestion that lack of oxygen accounted for the very unpleasant symptoms that had come to be associated with travel to the high mountains. He indicated that he and his fellow high mountain sojourners all became by degrees much distressed; a constant desire to vomit, together with vertigo were the most prominent symptoms and proved far more trying than the difficulty of breathing which we likewise suffered from. The distress, the weakness, and the desire to vomit certainly came as much from the lack of oxygen in these regions as from the rarity of the air.6

Although de Saussure and von Humboldt seemed to be near to a breakthrough in understanding some of the important mechanisms involved in high altitude illness, they were not in a position to see if their theories were really sound by way of systematic experimentation. However, no one else was prepared to tackle this question experimentally either, for more than half a century after von Humboldt’s prescient observations.2,7

Lower It Would Not Go.

Edward Whymper (1840-1911) of Matterhorn fame succeeded in making the first ascent of Chimborazo (6420 m) in 1880. In the classic account of his South American travels, he included detailed descriptions of his group’s altitude-related maladies. They also set up a mercury barometer (pictured here) on the summit of Chimborazo and measured the air pressure. They were surprised that the barometric pressure was so high (~358 mm Hg), given what they knew about pressures measured in the Alps of Europe. However, Whymper did not realize that this pressure was just about right for a mountain of this altitude in midsummer only two degrees of latitude away from the equator

With the publication of La Presson Bariometrique in 1878,8 Paul Bert made an experimental connection between the fall in barometric pressure, and the problems humans faced at high altitude. Bert is considered by many to be the father of modern high altitude physiology.7 However, fellow Frenchman and physician Denis Jourdanet prompted much of Bert’s work. Jourdanet had spent almost 20 years practicing medicine at high altitudes in Mexico, and had focused much of his attention on the effects of high altitude on humans. With Jourdanet’s subsequent encouragement and financial support, Bert was able to build one of the earliest pressure chambers in his laboratory. He was able to demonstrate that by breathing supplemental oxygen in hypoxic conditions, the symptoms of acute mountain sickness could be treated.7

Bert’s fortuitous meeting in the early 1870s with Jourdanet was to have far reaching consequences for the field of high altitude physiology. Bert and he shared enough medical interests to become friends and fellow-workers, with Jourdanet providing Bert with funds to establish a laboratory with a decompression chamber for the investigation of hypoxic phenomena. During the course of his high altitude field experiences, Jourdanet had formulated the hypothesis that blood contained less oxygen on high mountains because the atmospheric pressure was lower, calling this theory ‘barometric anoxemia’. With Jourdanet’s financial backing, Bert aimed to put this theory to the test with a series of laboratory studies that would ultimately make enormous strides in sorting out the puzzle of mountain sickness.

Paul Bert depicted working in his laboratory’s pressure chambers

Paul Bert depicted working in his laboratory’s pressure chambers

Bert utilized his laboratory pressure chamber to take animals to various levels of barometric pressure, doing this in conjunction with the provision of different oxygen percentages. He found no consistency in either the barometric pressure or the percentage of oxygen at which the animals were found to be in extremis, or at which they died. As a good experimentalist, he then decided to keep the percentage of oxygen constant in the pressure chamber but vary the chamber pressure. He found that in this circumstance, the animals consistently died more rapidly at lower chamber pressures. Taking his ideas one step further, Bert multiplied a given barometric pressure in the chamber by the percentage of oxygen, and found that these calculated values could also give predictable results. By doing this, he had applied Dalton’s law of partial pressure. Bert could thereby lay claim to a major advance in physiology, by showing that the partial pressure of oxygen, rather than barometric pressure or the percentage of oxygen alone, was responsible for the deleterious effects of hypoxia. Although it seems so obvious today as to be easily taken for granted, Bert was able to personally confirm his deduction that mountain sickness is caused by exposure to an environment with low partial pressures of oxygen.9

Although Bert did pioneering work with hemoglobin and oxygen transport, his study of high altitude (hypobaric) and high pressure (hyperbaric) environments, such as deep-sea diving, is the work for which he is primarily remembered. In 1878, Bert introduced his 1178 page magnum opus La Pression Barométrique, Recherches de Physiologie Expérimentale8 to the world (reprinted in English in 1943 as Barometric Pressure : Researches in Experimental Physiology6). La Pression Barométrique contained not only Bert’s experimental results, but also an encyclopaedic history of all that was then known or believed about high and low barometric pressures and mountain sickness.

Probably the best clinical description of the early references to the potentially deadly malady of HAPE occurred in the 1894 publication (1898 English translation) of Angelo Mosso’s seminal volume, Life of Man in the High Alps.10 Quite near to the time that Mosso’s original edition of Life of Man in the High Alps appeared, another documented case of what was likely HAPE occurred, this time near the summit of Mont Blanc. But in this instance it was fatal to the patient. Not long after an observatory was built quite near the summit of Mont Blanc in 1891, a young Chamonix doctor, Etienne Henri Jacottet, climbed quickly to this high altitude outpost, and then on to the summit of the mountain. Shortly afterward, he became very sick with pulmonary-related symptoms that precipitated his untimely demise. An autopsy was performed, and the report suggests this was, in retrospect, the first post-mortem examination of a case of HAPE.

The distinguished astronomer Jules Janssen was responsible for building the aforementioned observatory near the summit of Mont Blanc, the same observatory that Jacottet climbed to just before he died. Janssen believed that exertion was the foremost cause of mountain sickness, and arranged to have himself pulled up Mont Blanc on a sled. He was fascinated to discover that he experienced no symptoms of illness when ascending in this fashion, but noted that many of the 12 men who dragged him up the mountain succumbed to the unpleasant effects of mountain sickness.11 It is now recognized that while a sedentary ascent to altitude (especially if a great deal of height is gained quickly) is by no means insurance against altitude illness, hard physical labour combined with rapid ascent certainly increases the risk of sickness.

The misconception that HAPE was pneumonia (or a manifestation of heart failure) persisted for decades, and it was not recognized as a unique pathophysiological entity until 1960 in the English-speaking world. Nonetheless, it is somewhat surprising to note that in 1913, Thomas Ravenhill, a British medical officer employed by a Chilean mining company located approximately 4575 m above sea level, provided the first modern account of high altitude illness in a landmark paper.12 The mines were served by a railway, so he had the opportunity to observe miners suffering the effects of high altitude uncomplicated by the fatigue, cold or lack of food that confounded previous descriptions by explorers and mountain climbers. Ravenhill spent two years at the Chilean mines that became the setting for his clinical descriptions. He termed what we recognize today as acute mountain sickness (AMS) and high altitude cerebral edema (HACE). HACE was ‘puna’ of a nervous type because of its neurological signs and symptoms (‘puna’ being the local Chilean word for mountain sickness). HAPE was termed ‘puna’ of a cardiac type – although HAPE is clearly recognized today as a non-cardiogenic pulmonary edema. Ravenhill published his findings in 1913 in the Journal of Tropical Medicine and Hygiene. Since this journal was an obscure choice for an altitude-related article, Ravenhill’s report was all but forgotten in subsequent decades. In fact, it was not ‘rediscovered’ until 1964, when William H. Hall of the U.S. Army Research Institute of Environmental Medicine carried out an extensive literature search prior to writing a paper on AMS.13

Regardless of much of the English-speaking medical world forgetting about Ravenhill’s outstanding 1913 account of high altitude illness in Chile, key advances in the recognition of HAPE were, in reality, made in Peru. This was particularly true in connection with the Cerro de Pasco mine (at 4338 m) and the Chulec General Hospital in Oroya (at 3750 m). Several articles were published on HAPE between the late 1920s and the 1950s, but unfortunately all of these appeared in Spanish publications published in Lima, Peru. More about the ‘rediscovery’ of high altitude illness in the 1950s and 1960s (at least in the English-speaking world) will be discussed below.

Prior to the first successful penetration of the inner sanctum of Mt Everest in 1921, British explorers and mountaineers had for more than two decades shown a serious interest in planning a reconnaissance expedition to the mountain. Dr. Alexander M. Kellas (1868-1921) was one individual who was most intrigued by the possibility of climbing Everest.14

As the First World War approached its last year of conflict, Kellas published a paper in a 1917 issue of the Geographical Journal titled ‘A consideration of the possibility of ascending the loftier Himalaya’ 15. The most interesting section of Kellas’ article was titled ‘Physiological Difficulties’. Of the topics discussed, possibly the most attention-grabbing are the pressure chamber experiments and the physiology of acclimatization at the highest Himalayan altitudes then reached (7000 m as of 1917).

Shortly before the end of WWI, Kellas and John Scott Haldane undertook experiments on acclimatization to reduced atmospheric pressure at the Lister Institute in London, with the results later published in the Journal of Physiology.16 The two scientists spent several hours a day for four consecutive days in a hypobaric chamber at altitudes equivalent to 3536 m (day 1), 4877 m (day 2), 6400 m (day 3), and 7620 m (day 4). On day 4, with the barometric pressure at 312 mmHg, Haldane’s alveolar PCO2 was 19.8 and the PO2 was 30.1 mm Hg. Although he was able to do an impressive 3300 ft-lb/minute of work for four minutes (on an ergometer) before stopping because of exhaustion, the addition of one litre/minute of oxygen administered through a Haldane mask made the resumption of the work ‘quite easy,’ even when increased to 5000 ft-lb/minute, These results not only supported the assertion that even short periods of acclimatization increased altitude tolerance, but also showed how important the use of low-flow supplementary oxygen could be in improving performance during exposure to extreme hypobaric hypoxia. It is worthy of note that ‘extreme’ human experimentation such as this would be difficult, if not impossible, to reproduce today because of institutional human-subjects protection policies!

Over the course of the 30 years after the first extreme altitude (eg, > 8000 m) experiences of the pioneering (1922 and 1924) attempts on Everest, scientists pondered the question of whether it would be possible for humans to reach the highest point on earth. For some, oxygen seemed to be the only realistic way to achieve this.17 Italian physiologist Rudolfo Margaria had an interest in this question, and in the 1930s carried out a series of experimental studies in a low-pressure chamber. He found that at a barometric pressure of 300 mmHg – an altitude equivalent of roughly 7500 m – the maximum human power fell to zero. He consequently argued against the possibility of Everest ever being climbed without supplementary oxygen, even though the Everest pioneers such as George Mallory and Howard Somervell had broached the 8000 m mark sans supplementary oxygen.

Howard Somervell and George Mallory

Howard Somervell and George Mallory on the extreme right of this image, taken immediately after they had descended to advance base camp on Everest, after climbing higher than 8000 m for the first time in history in 1922 (Photo by George Finch, courtesy of Anne Russell)

Subsequently, Margaria collaborated with the aforementioned British physiologist, Joseph Barcroft, from Cambridge, and the two scientists travelled to Oxford to use the low-pressure chamber there. They aimed to determine if it was it was possible to ‘climb’ to a barometric pressure that is equivalent to that found on Everest’s summit, provided 100% oxygen was breathed. While they predicted it was possible, Barcroft concluded it was impracticable for a climber to reach the summit in this fashion given the weight of the supplementary oxygen apparatus available for the task. Shortly thereafter, the well-respected physiologist from Yale University, Yandell Henderson, analyzed data from acclimatized subjects at high altitude and produced a reasonable conclusion. After examining his calculations, Henderson found that the maximal oxygen consumption rapidly fell as an altitude equivalent to the summit of Everest was approached. He stated that near the top of Everest, “the rate of ascent must approach zero : in other words, a minimum of progress in an unlimited amount of time,” and therefore argued it would be impossible to ever successfully ascend Mt Everest without supplementary oxygen. Obviously, proclamations from even the most eminent of scientists do not always stand the test of time, as Everest has now seen many ascents without supplementary oxygen.

With World War II on the horizon in the late 1930s, increasing sophistication of combat aircraft posed problems for design engineers and pilots who were restricted by human physiological limitations encountered at high altitude. Simple gas laws hampered development of state-of-the-art aviation war machinery : supplementary oxygen delivered by mask had limited effectiveness in the very low barometric pressures above 10000 m (12000 m being the approximate upper limit of survival when breathing supplemental oxygen without a pressurized suit or cabin). Germany’s Air Ministry scientists, such as Hans Hartmann, sought to increase the physiologic ‘ceiling’ of pilots, and argued that high altitude acclimatization might effectively raise an aviator’s ceiling when he was utilizing supplementary oxygen from a mask. The German government, as a result, readily agreed to support Himalayan mountaineering expeditions in the late 1930s in order to provide a platform for physiological work that might potentially yield important insights into altitude tolerance and adaptation.18

It was well known by the late 1930s that humans developed an increase in circulating red cells at altitude. Talbott had demonstrated the marked increase in reticulocytes during acclimatization of lowlanders to high altitude on the 1935 International High Altitude Expedition to Chile that took place under the scientific leadership of Professor D. Bruce Dill from the Harvard Fatigue Lab. The main purpose of this expedition was, in fact, to study the changes in blood chemistry that occur at high altitude. Several decades earlier, however, Viault actually published the first work showing red cell increases in sea level natives when exposed to high altitude.19 Of special note here is that even though this mechanism is often used as a classical example of beneficial adaptation designed to serve humans at high altitude,

The extent to which benefit can be gained by increasing Hb concentration is fairly limited and indeed has been questioned as beneficial at all.9

In defense of physiologists of the pre-WWII era, there was not yet awareness that many ethnic groups of highland natives do not develop polycythemia as a result of life-long altitude residence. Thus, it was perhaps natural to overemphasize this element of acclimatization in the 1930s.

Most certainly, German scientists were world leaders in their understanding of high altitude physiology in the late 1930s when the global war became a reality. By 1945, the English-speaking countries had caught up with and exceeded the Germans in many areas of high altitude/aviation physiology. One example of this surge of interest in altitude physiology was an ambitious study, appropriately named ‘Operation Everest’, sponsored by the US Navy in 1946 and directed by investigators Drs. Charles Houston and Richard Riley. During the course of a 35-day stay in a decompression chamber, four men were slowly taken to a simulated altitude of 7620 m, after which a one-day ‘dash’ was made to the pressure equivalent of Everest’s summit. Two of the four subjects tolerated the summit ‘altitude’ for 20 minutes, and were even able to do some light exercise during this period of time. While the subjects’ acclimatization was not optimal after this relatively short ‘ascent’, the data gathered during the study provided new insights into adaptation to extreme altitudes. Perhaps most importantly (at least to mountaineers), Operation Everest provided evidence that man could survive while breathing only ambient air at an atmospheric pressure equivalent to that found at the highest point on earth.2

Not long after the end of World War II, eyes turned to Everest once again. British physician and physiologist LCGE ‘Griff’ Pugh was an undisputed post-WWII leader in investigation of problems germane to environmental physiology (including but not necessarily limited to high altitude physiology).20 In addition to research carried out in his London laboratory, he also performed extremely important field research in the spring of 1952 on and around the famous 8000 m peak Cho Oyu, not far from Everest. This wide-ranging field study examining the physiological problems that humans face at extreme altitude was reported in an extensive document that included investigations on hydration, oxygen equipment, food, and clothing. As quoted in Ward and Milledge (2002)

The expedition to Cho Oyu in 1952 was organized by the Joint Himalayan Committee of the Alpine Club and the Royal Geographical Society. Apart from the climbing objective, the expedition was designed to form a nucleus of climbers capable of attempting the ascent of Mount Everest in 1953. A physiologist [Pugh] accompanied the party to study the use of oxygen at high altitude, and problems of acclimatization and equipment.21

The work Pugh instigated in his laboratory in 1951 and on the Menlung La (near Cho Oyu) in 1952 was to be continued on Everest; he was becoming firmly convinced that the most efficient way to study man at altitude was in the field rather than in a lab setting. Pugh’s thinking was eventually realized in a full-scale way seven years hence. His plans for a large-scale, long-term, high altitude field study came to fruition in the form of the World Book Encyclopaedia-funded Himalayan Scientific and Mountaineering (Silver Hut) Expedition of 1960-61, which was led by Sir Edmund Hillary, with Pugh serving as the scientific leader. The aim of the programme was to study the physiological effects that long-term high altitude (5800 m) living had on native lowland dwellers. This was coupled with a sister programme of Yeti-hunting, building a school for the Sherpas, and an attempt to climb Makalu (8462 m) without supplementary oxygen.

There were several reasons for the insistence of spending months on end during the winter of 1960/61 at such a high altitude. The expedition was primarily concerned with studying the physiological effects of native lowlanders spending an extended period of time at nearly 6000 m. Mountaineers had obviously visited higher altitudes for many decades, and permanent high altitude residents living at elevations greater than 4500 m had been studied. However, it was of considerable scientific interest to study sojourners residing for many months at the aforementioned altitude, to better understand not only the acclimatization process, but high altitude deterioration as well.

The attempt on Makalu, which took place in the spring of 1961 (following a winter’s stay at 5800 m for the Silver Hut residents), did in fact provide an object lesson in altitude-induced physical deterioration. They hoped that the residents would become so fit and acclimatized that when spring came, they could reasonably climb Makalu without supplementary oxygen. This was a very sensible hypothesis given the state of knowledge at the time. However, physical deterioration due to extended living at such an altitude proved to be a greater factor than any of the scientists had anticipated.

Even though the Makalu expedition had mountaineering as its primary aim, science was not neglected. Physiological testing was carried out at advanced base camp (6300 m), and in addition, Michael Ward and John West were able to conduct measurements of VO2max on Makalu Col at 7400 m using a stationary bicycle. This was an altitude record for such a feat, and VO2 max measurement at a higher altitude was only accomplished very recently (in May of 2007) on the South Col of Everest at 8050 m.

The early 1960s were an important period in the growing understanding of not only high altitude physiology, but high altitude medicine as well. HAPE had already been recognized as edema of the lungs (particularly in newcomers) by Peruvian medical professionals practicing in high altitude regions. This was, however, not brought to the general attention of the modern English-speaking medical community until 1960 when Drs Herb Hultgren and Warren Spikard published an account of a two week visit to Chulec General Hospital in La Oroya, Peru.22 At La Oroya, they had the opportunity to review the medical records of 41 patients diagnosed with high altitude illnesses and to make daily rounds with house staff. Although Angelo Mosso may have described HAPE in English in 1898, and Ravenhill spoke of an affliction he termed ‘puna of a cardiac type’ (ie, HAPE) in 1913, Hultgren and Spikard’s 1960 paper was very (if not more) clinically relevant. Their article was titled ‘Medical Experiences in Peru’, and it appeared in the Stanford Medical Bulletin in May of 1960. It proved to be the first account of HAPE published in English where the salient clinical and investigative findings were very clearly reported.

Unfortunately, this account did not have the impact it might ideally have deserved. Charles S. Houston published a case report titled ‘Acute Pulmonary Edema of High Altitude’ in the New England Journal of Medicine (8 September, 1960), which is generally recognized as the most influential publication in the rediscovery of HAPE in the English-speaking medical literature.23 Dr Houston’s report featured a 21-year-old ski-mountaineer who had become so ill with severe dyspnea, weakness, and productive cough when crossing a 3660 m pass in the Colorado Rockies in late December 1958 that evacuation became necessary. Houston was involved in the rescue and his examination of the patient after evacuation revealed cyanosis, marked orthopnea, and dyspnea, and both lung fields filled with coarse to medium rales. A radiograph of the chest showed a normal cardiac silhouette with mottled infiltration throughout the right lung field, with less marked infiltration on the left side. The diagnosis was not clear, however, and in May 1959 the patient was examined by a cardiologist in Denver. The cardiologist suggested that there was no evidence on which to base a diagnosis of any form of organic cardiovascular disease, but uncertainty persisted about the etiology of what seemed to be pulmonary edema (as opposed to pneumonia). However, by the time Houston’s 1960 New England Journal article about this case appeared, he had concluded that the malady was acute pulmonary edema without heart disease prompted by the sum of high altitude, cold, and heavy exertion – in other words, HAPE.

By 1960, HACE had yet to be identified as a distinct, severe form of high altitude illness. In fact, little was known about the pathophysiology (or treatment) of AMS during this period, and the cerebral form of high altitude illness that was first clinically described in the English language by Thomas Ravenhill in 1913 had all but been lost to the medical world. As mentioned above, it was not rediscovered until 1964 during an extensive literature done for a paper on AMS.13 Interestingly enough, 1964 was also the year that Fitch published a case report on a 1960 episode of severe AMS on Mt McKinley.24 This represented another ‘rediscovery’ of altitude illness – specifically that of HACE – separated from Ravenhill’s original clinical description by 51 years.

The aforementioned 1961 Makalu attempt without supplementary oxygen did not add support to the argument that Everest could be climbed unaided by the tanks of oxygen assumed to be a necessary ‘accessory’ by those attempting the peak. However, the final proof that humans can reach the summit of Mt Everest without such adventitious aids was conclusively provided by Reinhold Messmer and Peter Habeler in the spring of 1978. Messner describes the experience on summit day in terms that are rather expressive :

On reaching the top, I sit down and let my legs dangle into space….Now, after the hours of torment…I have nothing more to do than breathe, a great peace floods my whole being. I breathe like someone who has run the race of his life and knows that he may now rest forever…In my state of spiritual abstraction, I no longer belong to myself and to my eyesight. I am nothing more than a single, narrow, gasping lung, floating over the mists and the summits (Messner 1979).

This moving account may not completely do justice to the emotions of the day, as it was no doubt written sometime after the expedition when Messner was in a reflective mood. More immediately believable is Habeler’s statement to the author (personal communication, 2007) that on summit day they realized they were climbing into the unknown, in marginal weather at that, and much of it was simply a frightening experience even for these vastly experienced alpinists. Habeler recalled worrying about potential (and permanent) damage he might be doing to himself by summiting Everest without supplementary oxygen. Nonetheless, this event was undoubtedly an epochal event in the history of high altitude physiology. Two years later Messner summited Everest again, this time not only climbing without supplementary oxygen, but in addition, doing it strictly as a one-man show by climbing the entire North Col/Ridge route solo.

The tremendous achievements of Habeler and Messner renewed interest in the physiological challenge offered by extreme altitudes, and this caught the attention of research scientists interested in human physiology in extreme environmental circumstances. Shortly before the aforementioned landmark 1978 Everest ascent unaided by supplementary oxygen, University of California San Diego physiologist John B. West, MD, PhD and colleagues had decided to commence the organization of a special physiological expedition to attempt to obtain measurements on the upper reaches of the world’s highest peak – and if possible, on the summit itself. The design of the expedition was heavily influenced by the previously mentioned 1960-61 Silver Hut Expedition. A sophisticated prefabricated field laboratory allowing for an extensive physiological programme to be carried out - similar to the Silver Hut - was to be erected at Everest Base Camp, with a second similar structure placed in the Western Cwm at an elevation approximately 1000 m higher on the mountain. A primary reason the Silver Hut experience proved to be such an important point of departure for this proposed expedition was that three members of the Silver Hut Expedition actually took part in the new venture – Sukhamay Lahiri, James S. Milledge, and John B. West.

This ambitious and rather audacious concept became a reality in 1981 through the dedicated work of West and his team, and became known as the American Medical Research Expedition to Everest (AMREE). The basic plan was to obtain a series of physiological measurements at four sites along the standard southern (South Col) route on the mountain – base camp (17,700 ft or 5400 m), advanced base in the Western Cwm (20,700 ft or 6300 m), Camp 5 on the South Col (26,400 ft or 8050 m), and the summit of Everest itself (29,028 ft or 8848 m). For the climbing and science that occurred above base camp, 10 tons of equipment had to be carried through the treacherous Khumbu ice fall.

The experience gained during the Silver Hut research showed that it was possible to make basic measurements at extremely high altitudes, such as the measurements of VO2 max at 7440 m and alveolar gas samples up to 7830 m – both obtained during the attempt to climb Makalu (8481 m) without supplementary oxygen in the spring of 1961. Furthermore, the possibility of obtaining data on the summit of Everest was a tremendously fascinating prospect, largely because how close this altitude is to the limit of human tolerance to hypoxia. Although Norton climbed to within 300 m of the summit of Everest in 1924 sans bottled gas, we know that it wasn’t until Messner and Habeler’s incredible feat in 1978 that the last 300 m were surmounted unaided by supplementary oxygen. While Messner and Habeler took both the scientific and mountaineering worlds by surprise, some people (at least initially) simply could not believe they had done what they claimed. Indeed some physiologists who had studied human work capacity during extreme hypoxic stress concluded that surmounting the upper reaches of Everest without supplementary oxygen was nothing short of impossible.

Of course, just as in the case of breaking the perceived barrier of the four-minute mile, Messner and Habeler’s 1978 feat opened the floodgates of possibility on Everest. We must remember, after all, that the mind has the potential to drive the body to accomplishments that are at times beyond comprehension, and without doubt some human bodies are simply better ‘machines’ at extreme altitude. Such inter-individual variation in physiological capacity (and personal motivation) is what makes the study of such phenomena in environmental extremes so fascinating on one hand and so maddening on the other.

AMREE was fortunate enough to be able to obtain some measurements on the summit of Everest, the most notable of these being alveolar gas samples obtained by Dr Chris Pizzo on 24 October 1981. Such measurements were invaluable, as they clearly suggested the profound physiological changes to which the human body must adapt in order to operate at such extreme altitudes. And as scientifically stimulating as AMREE (and various other subsequent high altitude studies) have proved to be, the question of why dramatic differences exist between individuals in their ability to adapt or acclimatize to high altitudes has largely remained unanswered. However, the 2007 Caudwell Xtreme Everest (CXE) Medical Research Expedition offered a unique opportunity to study how humans adapt to hypoxia. This field expedition set out to better understand why dramatic differences exist between individuals in their ability to adapt or acclimatize to low levels of oxygen. More than 200 volunteers trekked to Everest Base Camp to be subjects of 60 investigators in a series of experiments designed to investigate why there is such variation in people’s ability to perform effectively at altitude. At the same time, higher on the mountain, climbing doctors (and medical students) made novel measurements at the edge of the human physiological envelope, trying to define the limits of tolerance of hypoxia.

The CXE goal on the summit of Everest had been to measure the level of oxygen in the arterial blood of some of the team, in order to make a measurement very close to the limit of human tolerance of hypoxia. It is known that the level of hypoxia at the summit of Everest is close to this limit for several reasons. The first 63 successful summiteers all used supplementary oxygen; it was nearly 25 years after Hillary and Tenzing’s first ascent that Messner and Habeler succeeded in reaching the summit without supplemental oxygen. To this day only about 5% of those who reach the summit of Everest do so without using supplemental oxygen. Even the subtle reduction in barometric pressure that occurs during winter may be enough to make the summit unattainable breathing ambient air except by a very few individuals. Only one individual (a Sherpa) has so far reached the summit under winter conditions without supplemental oxygen. Sadly, on the CXE summit days the conditions on top were too cold and windy to draw arterial blood. The team did manage, however, to obtain four samples at 8400 m and these are the highest arterial samples ever obtained, by a margin of over 2000 m. The levels of oxygen in these samples was lower than has previously been measured in humans and are similar to the lowest levels ever measured in any mammal. The two other comparable values that have been identified have been in diving seals returning to the surface after a long dive and in the human fetus in the uterus.

The history of man’s experience with the low atmospheric pressures that is briefly recounted here highlights the reality that the medical consequences of ‘operating’ in such an environment can, at times, be quite serious. However, it is also clear that healthy humans fortunately have an ability to safely tolerate high altitude to an amazing degree, provided this environment is approached with a well-informed understanding of the inherent risks involved. Although many of the mysteries of high altitude have been solved, much work remains to be done.

An article on history of high altitude medicine, this is an abridged version of a book chapter first published in Rodway G. Weber D, McIntosh S. (2016). Mountain Medicine and Technical Rescue. Carreg, United Kingdom. Reprinted with permission.


  1. Rodway GW, Muza SR. Fighting in thin air : operational wilderness medicine in high Asia. Wilderness Environ Med. 2011; 22:297-303.
  2. Houston CS. The growth of knowledge about air, breathing, and circulation as they relate to high altitude. In : Hornbein TF, Schoene RB, eds. High Altitude : An Exploration of Human Adaptation. New York: Marcel Dekker, Inc.; 2001.
  3. Haider MM. The Tarikh-i-Rashid : History of the Mongols in Central Asia. Lahore : Book Traders; 1894.
  4. West JB. From classical Greece to the end of the seventeenth century. In : High Life : A History of High Altitude Physiology and Medicine. New York : Oxford University Press; 1998 : 1-39.
  5. Saussure HBd. Voyages Dans les Alpes. Geneva : Chez Barde, Manget et Compagnie; 1786.
  6. Bert P. Barometric Pressure : Researches in Experimental Physiology. 1st US ed. Columbus, OH : College Book Company; 1943.
  7. West JB. Eighteenth century to Paul Bert. In : High Life : A History of High Altitude Physiology and Medicine. New York : Oxford University Press; 1998 : 40-73.
  8. Bert P. La Pression Barométrique: Recherches de Physiologie Expérimentale. Paris, France : Masson; 1878.
  9. West JB, Schoene RB, Luks AM, Milledge JS. High Altitude Medicine and Physiology. Boca Raton, FL: CRC Press; 2013.
  10. Mosso A. Life of Man on the High Alps. London : T. Fisher Unwin; 1898.
  11. Whymper E. Travels Amongst the Great Andes of the Equator. London : John Murray; 1891-2.
  12. Ravenhill TH. Some experience of mountain sickness in the Andes. J Trop Med Hyg. 1913;16:313-20.
  13. Hall WH, Barila TG, Metzger EC, Gupta KK. A clinical study of acute mountain sickness. Arch Environ Health. 1965;10:747-53.
  14. Mitchell IR, Rodway GR. Prelude to Everest. Edinburgh, UK: Luath Press Ltd; 2011.
  15. Kellas AM. A consideration of the possibility of ascending the loftier Himalaya. Geogr J. 1917;49:26-47.
  16. Haldane JS, Kellas AM, Kennaway EL. Experiments on acclimatization to reduced atmospheric pressure. JPhysiol. 1919;53:181-206.
  17. Sale R, Rodway G.Everest And Conquest In The Himalaya. United Kingdom : Pen and Sword Books Ltd.; 2011.
  18. Rodway GW, Ulrich C. Luft and physiology on Nanga Parbat : the winds of war. High Alt Med Biol. 2009;10:89-96.
  19. Viault F. On the large increase in the number of red cells in the blood of the inhabitants of the high plateaus of South America. In : West JB, ed. High Altitude Physiology. Stroudsburg, PA : Hutchinson Ross Publishing Company; 1981.
  20. Tuckey HP. Everest, the First Ascent: How a Champion of Science Helped to Conquer the Mountain. Guilford, CT: Lyons Press; 2013.
  21. Ward MP, Milledge JS. Griffith Pugh, pioneer Everest physiologist. High Alt Med Biol.2002;3:77-87.
  22. Hultgren H, Spickard W. Medical experiences in Peru. Stanford Medical Bulletin. 1960;18:76-95.
  23. Houston CS. Acute pulmonary edema of high altitude. N Engl J Med.1960; 263:478-80.
  24. Fitch RF. Mountain sickness : A cerebral form.Ann Intern Med. 1964; 60:871-6.

George W. Rodway, PhD, represents a combination of scientific researcher, mountaineer, and science writer. An Associate Clinical Professor at the University of California, Davis (USA), his academic work focuses on the cardiopulmonary response to hypoxia, and it has on occasion presented him with the opportunity to climb mountains with scientific intent. An active mountaineer since the late 1970s, his scientific interest in high altitude began with the seasons he spent working as a medic on high altitude ranger patrols for the US National Park Service on Denali (Mt. McKinley, 6194m) in Alaska. He has climbed in Canada, Mexico, Europe, the US and the Himalaya. His interest in the history of science, especially as it concerns high altitude mountaineering, has given rise to many books and articles, including the soon-to-appear textbook he has edited, Mountain Medicine and Technical Rescue. He serves international organizations as well such as the International Society for Mountain Medicine and the Medical Commission of the Union Internationale des Associations d’Alpinisme (UIAA). He is a Life Member of the Himalayan Club, and a member of both the (UK) Alpine Club and American Alpine Club.

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