Barcroft's bold assertion: All dwellers at high altitudes are persons of impaired physical and mental powers

Abstract

Barcroft's bold assertion that everyone at high altitude has physical and mental impairment compared with sea level was very provocative. It was a result of the expedition that he led to Cerro de Pasco in Peru, altitude 4300 m. Although it is clear that newcomers to high altitude have reduced physical powers, some people believe that this does not apply to permanent residents who have been at high altitude for generations. The best evidence supports Barcroft's contention, although permanent residents often perform better than acclimatized lowlanders. Turning to neuropsychological function, newcomers to high altitude certainly have some impairment, and there is evidence that the same applies to highlanders. However the notion that permanent residents are impaired is anathema to many people. For example the eminent Peruvian physician Carlos Monge took great exception to Barcroft's remark and even attributed it to the fact that Barcroft was suffering from acute mountain sickness when he made it! Monge referred to ‘climatic aggression’, by which he meant the negative consequences of the inevitable hypoxia of high altitude. Recent technological advances such as oxygen enrichment of room air can overcome this ‘aggression’. This might be useful in some settings at high altitude such as a nursery where newborn babies are cared for, and possibly operating rooms where the surgeon's dexterity may be enhanced. Other situations might be dormitories, conference rooms, and perhaps some school rooms. These constitute possible ways by which the effects of Barcroft's assertion might be countered.

Joseph Barcroft (1872–1947) was an eminent British physiologist who made many important contributions to high altitude physiology. These include leading the International High Altitude Expedition to Cerro de Pasco, Peru, in 1921–1922 (Barcroft et al. 1923), a remarkable 6 day exposure of himself to increasing simulated altitudes in a small sealed chamber (Barcroft et al. 1920), and a chamber study of the possibility of ascending Mt Everest while breathing 100% oxygen (Barcroft et al. 1931). He also helped to demolish the theory that the lung could secrete oxygen at high altitude as had been championed by J. S. Haldane (Haldane, 1922). Barcroft summarized much of his work in a very readable monograph, Lessons from High Altitudes (Barcroft, 1925).

However, in spite of his major contributions in this area, it should be pointed out that Barcroft is actually best known for his research in two other areas, the physiology of haemoglobin, and neonatal physiology. Barcroft's contributions in these topics were discussed in two large international meetings, the conference on haemoglobin held in memory of Barcroft shortly after his death (Roughton & Kendrew, 1949), and the Sir Joseph Barcroft Centenary Symposium on fetal and neonatal physiology in 1972 (Cross, 1973). These two meetings emphasize the extraordinary range of Barcroft's contributions, and the first is notable for the eight introductory tributes from his peers, all of whom were Fellows of the Royal Society.

The present article concentrates on one of Barcroft's most provocative statements, made 90 years ago, and that still contains much food for thought. It occurs in the last chapter, titled ‘Acclimatization’, in Lessons from High Altitudes (Barcroft, 1925), and summarizes some of Barcroft's views on the effects of high altitude on the human being. The section reads:

‘The acclimatised man is not the man who has attained to bodily and mental powers as great in Cerro de Pasco as he would have in Cambridge (whether that town be situated in Massachusetts or in England). Such a man does not exist. All dwellers of high altitudes are persons of impaired physical and mental powers. The acclimatised man is he who is least impaired, or in other words he who has made least demand upon his reserve.’

First we should be clear about what Barcroft means by ‘dwellers’. It is clear from reading the monograph that Barcroft includes all people who are living at high altitude be they visitors from sea level, sojourners (that is, lowlanders who have been at high altitude for a few years), or permanent residents who have been there for generations. In particular, there is no doubt that Barcroft is including the last group because in the same chapter he refers to some of the physiological features of the permanent residents (highlanders). For example on the second page of the chapter on acclimatization we read, ‘In the case of the small‐bodied but large‐chested Cholos [Barcroft's incorrect name for the permanent residents] one may suppose that the quantities of oxygen used and CO₂ given out are proportional in quantity to the body surface.’ So here we have Barcroft stating unequivocally that all people who find themselves at high altitude have impaired physical and mental powers.

The monograph describes the expedition that took place in 1920–1921 to Cerro de Pasco, a mining town in the Andes about 200 km to the north‐east of Lima. The present town is built around a gigantic open‐cut mine that produces copper, silver, lead and zinc. The population today is some 70,000 people but of course in Barcroft's time was much less. The altitude is often given as 4300 m although, because it is on a slope, higher altitudes are also stated. As indicated above, Barcroft refers to three groups of people. The first are the visitors who were the expedition members, mainly scientists from Cambridge and Harvard Universities. They spent only a month or so at this altitude. The next group were the so‐called sojourners, who were engineers and clerical workers connected with the mine. Their original residence was near sea level but they had been at Cerro de Pasco for many months or several years. The expedition was able to make a number of measurements on these people including the $P_{{\mathrm{O}}_2}$ of the arterial blood. Finally there were the permanent residents of high altitude, who were also studied to some extent. This mix allows us to set up a matrix as shown in Table 1 where we can separately examine the available evidence for both physical and mental powers for visitors, sojourners and permanent residents.

Table 1.

Modern assessment of Barcroft's assertion

		? Impaired	? Impaired
	Time at high	physical	mental
Subjects	altitude	powers	powers
Visitors	Few weeks	Yes	Yes
Sojourners	Up to a few years	Probably	Probably
Permanent residents	Generations	Yes	Yes

Visitors to high altitude

Physical powers

It is well accepted that lowlanders who go to high altitude for short periods have a reduced exercise ability. Figure 1 shows the results of a series of measurements made by Cerretelli (1980) and others indicating that when the barometric pressure is reduced from 760 mmHg (sea level) to about 480 mmHg, the maximal oxygen consumption falls to about 40% of the sea level value. The plot is interesting because it includes both lowlanders exposed to acute hypoxia and those that have undergone acclimatization. In describing the figure, Cerretelli makes the statement, ‘It is practically impossible to find any difference in maximal performance between subjects acutely exposed to mild hypoxia and those acclimatized to it.’ Since acclimatization has so many beneficial effects, for example in relieving acute mountain sickness, this statement is counter‐intuitive. The graph also includes measurements made in decompression chambers at simulated high altitudes, and the results of breathing hypoxic mixtures. There are also a few measurements on permanent residents of high altitude. The results on these people will be discussed in more detail later. The clear message is that hypoxia reduces exercise ability, as would be expected on general physiological principles.

Figure 1. Maximal oxygen consumption as a percentage of the sea‐level value plotted against barometric pressure and altitude .

Open symbols, acute hypoxia; filled symbols, chronic hypoxia; crosses, altitude natives. From Cerretelli (1980), redrawn from Åstrand & Rodahl (1970) with the addition of data from Cerretelli & Margaria (1961), *; Elsner et al. (1964), ×; Cerretelli et al. (1967), and Cerretelli (1976b), □ in a decompression chamber and ⊡ breathing hypoxic mixtures Δ; on 32 lowlanders acclimatized to 5350 m. In parentheses, number of subjects. With permission.

Very severe hypoxia results in extremely limited levels of maximum exercise, as shown in Fig. 2. This indicates that breathing air with an inspired $P_{{\mathrm{O}}_2}$ of 42 mmHg, equivalent to that on the summit of Mt Everest, results in a maximal oxygen consumption of only about 1 litre min⁻¹. This is the oxygen consumption of someone walking slowly on the level. It is a remarkable coincidence that the highest altitude in the world is very near the limit of human tolerance to hypoxia.

Figure 2. Maximum oxygen uptake plotted against the inspired $P_{{\mathrm{O}}_2}$ .

The lower line shows data from the 1960–1961 Silver Hut expedition (Pugh et al. 1964). The upper line is from the 1981 American Medical Research Expedition to Everest and shows the oxygen uptake for the summit $P_{{\mathrm{O}}_2}$ was just over 1 l min⁻¹ (West et al. 1983). With permission.

Mental powers

There is strong evidence that lowlanders who ascend to high altitude for short periods develop impairment of neuropsychological function. Actually some of the first measurements in this area were made by Barcroft during the Cerro de Pasco expedition. The procedures included a memory test of a 10‐integer number, a multiplication test consisting of multiplying two numbers of five digits each, an alphabet test where one of the 26 letters on a page was duplicated, and a clock test in which a mirror image was shown of the dial. Somewhat to Barcroft's surprise, the results of the tests were the same in Cerro de Pasco as at sea level. However the tests took longer to administer, and he noted that the expedition members spent a longer time with simple problem solving with the result that there was a lot of ‘bungling’ as he put it. He concluded that if an expedition member concentrated on a problem at high altitude, he could usually solve it accurately, but concentration was impaired and simple errors were frequently made.

Seventeen years later a classical series of measurements was made by MacFarland (1937 a,b, 1938 a,b) during the International High Altitude Expedition to Chile, where studies were carried out up to an altitude of 4700 m. The measurements showed that many aspects of neuropsychological function were impaired including arithmetical tests, writing ability, and the appearance and disappearances of after‐images following exposure to a bright light. In addition there were increased memory errors, and errors in concentration.

The studies by MacFarland were classical but since that time many investigators have described impaired cognitive and other central nervous system functions in newcomers to high altitude. These include studies by Cahoon et al. (1972), Hornbein et al. (1989), Pavlicek et al. (2005), Zhang et al. (2011), and Aquino Lemos et al. (2012). A useful review is by Yan (2014). Night vision is particularly vulnerable to hypoxia. Some changes in cognitive function such as complex reaction times have been described at altitudes as low as 1520–2440 m (Denison et al. 1966)

Interesting results were reported by the 1981 American Medical Research Expedition to Everest. It was not surprising that measurements at altitudes over 6000 m showed neuropsychological impairment including short‐term memory and a finger‐tapping test of manipulative skill. What was unexpected was that when the expedition members returned to sea level, both tests were still abnormal compared with pre‐expedition measurements (Townes et al. 1984). Residual impairment of neuropsychological function following ascent to very high altitude has been described many times since (Hornbein et al. 1989). These results are consistent with sophisticated measurements of brain morphology, for example by MRI, that have shown changes in subjects after ascent to 6206 m (Zeng et al. 2012).

Sojourners

As indicated above, Barcroft used this term to refer to the mining engineers and clerical staff who had previously lived at low altitude but were spending a few years in Cerro de Pasco in connection with the mine. Relatively little research has been done on lowlanders spending extensive periods at high altitude and so the following conclusions are tentative.

Physical powers

Barcroft (1923) when describing his experiences in Cerro de Pasco stated, ‘The engineers and clerical staff, with varying numbers of years’ experience of work at that altitude, seemed to be unanimous in holding that up there they were definitely incapable of doing their own sea‐level standard of work whether mental or physical.’ However, he did not make any actual measurements of work capacity on this group.

One approach to this issue is to interpolate using known data on visitors to high altitude described above and permanent residents considered below. In both these groups there is evidence that physical power is impaired at high altitude, and therefore it seems reasonable to conclude that this is the case for sojourners, too.

Mental powers

Again we have the anecdotal statement from Barcroft that the engineers and clerical staff at the Cerro de Pasco mine who had spent a varying number of years at high altitude were unanimous in stating that their mental standard of work was less than at sea level. Anecdotally again, physicians who have spent many months at the Himalayan Rescue Association aid post in Pheriche, Nepal, altitude 4370 m, have complained that they frequently made arithmetical errors when trying to balance the books. However, formal neuropsychometric measurements in lowlanders with long exposure to high altitude have not been reported.

Permanent residents

Physical powers

There is convincing evidence that highlanders, that is, people who have been born and bred at high altitude for generations, have a reduced work capacity at high altitude compared with sea level. This may come as a surprise to some people who are impressed by the apparent extraordinary physical ability of some highlanders. For example, Barcroft and his group were amazed at the ability of the residents of Cerro de Pasco to play football (soccer). Along the same lines, the climbing record of Sherpas in the Himalayas is striking. For example only three people have reached the summit of Mt Everest 10 or more times, and all of these have been Sherpas.

However there are studies on the maximum oxygen consumption of permanent residents of high altitude indicating that their performance is impaired compared with sea level. Indeed Fig. 1 shows that the maximum oxygen consumption of highlanders falls on approximately the same curve as that for lowlanders. Other studies confirm the reduction in maximal oxygen consumption of highlanders with increasing altitude. For example, Elsner et al. (1964) studied Andean highlanders and showed falls in maximal oxygen consumption as the altitude increased from near sea level to 4540 m and then to 6400 m. They also found that in two subjects who breathed sea level air at an altitude of 4540 m, the maximum oxygen consumption increased by about 30%.

In spite of the fall in maximal oxygen consumption of highlanders as the altitude is increased, Brutsaert (2008) concluded that Andean highlanders have a higher physical work capacity in hypoxia than some acclimatized lowlanders. Consistent with this, the rate of fall of maximum oxygen consumption with increasing altitude is less in highlanders than acclimatized lowlanders. He attributed this to two possible factors. One is the additional growth and development at high altitude stimulated by the hypoxia as measured in Peruvian Quechua (Kiyamu et al. 2014). The other in the case of Andean and Himalayan residents is genetic factors that result in higher limits to exercise performance. Note, however, that all studies show a decrease in work capacity in highlanders as the altitude increases.

It is worth noting that at extreme altitudes, say over 6000 m, highlanders such as Sherpas have a greatly reduced maximum exercise capacity compared with their capacity at lower altitudes. This is evidenced by the reduced load carrying at very high altitudes. The maximum load is smaller and the climbing speed is slower. Indeed it would be inexplicable if this were not the case from what we know of the physiology of exercise. However, some Sherpas clearly have exceptional exercise performance under these conditions compared with well‐acclimatized lowlanders.

Mental powers

The issue of whether permanent residents of high altitude have neuropsychological impairment as a result of the hypoxia to which they are exposed is a difficult one. First, neuropsychological function varies greatly among individuals, and in addition it is very much influenced by cultural factors. Therefore the best way to obtain a definitive answer to this question is to make measurements on the same individuals at different levels of oxygenation. This could be done by making the same measurements at high and low altitudes, or by making the measurements at high altitude with the subject breathing ambient air and then repeating these with the subject breathing an enriched oxygen mixture (see below). Apparently no such measurements have been made.

Nevertheless there is strong evidence that permanent residents of high altitude have impaired mental powers compared with sea level. Yan (2014) has recently reviewed studies on the neuropsychological function of highlanders. In one study Hogan et al. (2010) tested what were believed to be comparable groups of infants, children and adolescents who lived at altitudes of about 500 m, 2500 m and 3700 m in Bolivia. The measurements were made at the altitude at which the subjects lived. It was reported that motor speed, cognitive processing speed, and cerebral blood velocity were reduced with increasing altitude. The authors concluded that the results could be explained by a direct effect of hypoxia on brain functioning, or a slower rate of central nervous system development in the hypoxic environment.

In another pair of studies, young adults who were third or fourth generation descendants of immigrants to high altitude were compared with a matched control group who were born and raised at low altitude. The two groups were matched in age, sex ratio, educational level, ancestral lines and haemoglobin concentration, and were studied at the same low altitude. The original high altitude residents had a reduced accuracy in a verbal memory task as shown in Fig. 3 (Yan et al. 2011 b). There were also longer reaction times in verbal and spatial working memory tasks (Yan et al. 2011 a). In these studies, blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) showed that the high altitude subjects had decreased activation of some brain regions compared with the low altitude subjects. The conclusion was that brain development was slowed in the hypoxia of high altitude.

Figure 3. Reaction times and response accuracy measured in a verbal working memory task in highlanders and lowlanders who were college students matched for age, sex and socioeconomic status .

Compared with the sea level group, the high altitude group responded slower and less accurately. The differences were significant at the P < 0.05 level. From Yan (2011 b). With permission.

An earlier study using positron emission tomography (PET) showed that high altitude residents had decreased cerebral glucose metabolism in the frontal cortex (Hochochka et al. 1994). A reservation about these studies is whether the control group had the same educational and cultural background as the other group and therefore was truly comparable.

These studies raise the issue of whether the growth of the central nervous system is slowed by the hypoxia. Some animal experiments support this. For example a study in mice showed that decreased myelination in the corpus callosum was seen when the animals were raised in a hypoxic environment, and that this was irreversible when the oxygen level was raised (Kanaan et al. 2006).

From a broad biological point of view it might be expected that the inevitable hypoxia associated with living at high altitude would affect the function of the central nervous system. We know that the brain metabolism is very oxygen dependent, and also that the oxygen consumption of the brain is about 20% of the total oxygen uptake of the body whereas its weight is only about 2% (Guyton & Hall, 1996). Certainly neuropsychological function is impaired in lowlanders at high altitude.

It is pertinent here to discuss the design of a possible experiment to determine whether permanent residents of high altitude have impaired mental powers because of the hypoxia. This would presumably be carried out on either the Tibetan Plateau, or at high altitude in the Andes because this is where most highlanders live. The study would be made on a group of highlanders who would serve as their own controls. For example the experiment could be done in a room that could be oxygen‐enriched as discussed below. A battery of neuropsychometric tests would be administered under two or possibly more conditions. One would be with the subjects breathing ambient air, and the other would be with the subjects breathing an oxygen‐enriched mixture which would simulate a reduction in altitude. It would be essential to set up conditions such that the subjects were unaware of the inspired oxygen partial pressure. Also there is a learning effect in some of these tests and the order in which the different inspired gases were given would have to be randomized. The battery of neuropsychometric tests should be chosen to fit with the cultural background of the subjects. Possibly a preliminary study would need to be done to determine the power that would be required for statistical purposes. This would not be a particularly difficult experiment to carry out, but apparently has not yet been done.

A possible alternative design would be to make measurements on a group of subjects both at high altitude and at sea level. However, this would presumably be more expensive because of the costs of transportation. Another advantage of carrying out the study at high altitude using an oxygenated room is that it would allow repeat measurements to be easily made.

The angry response of Carlos Monge Medrano to Barcroft's assertion

Carlos Monge Medrano (1884–1970) was a physician on the faculty of the University of San Marcos in Lima when Barcroft passed through in 1920 and 1921 en route to, and returning from, Cerro de Pasco. Monge was a leader in high altitude medicine in Peru but did he not meet Barcroft at the time. Perhaps this is not surprising. Barcroft was a foreign academic physiologist while Monge was a practicing physician, and probably they did not know about each other.

However when Monge read Barcroft's monograph, Lessons from High Altitudes (Barcroft, 1925), he was incensed by the assertion that the Peruvian highlanders were persons of impaired physical and mental powers. He subsequently wrote a book, Acclimatization in the Andes: Historical Confirmation of ‘Climatic Aggression’ in the Development of Andean Man, which was published by Johns Hopkins University Press (Monge, 1948). Monge wrote the book in Spanish and it was translated into English by Donald Brown, who was a faculty member of Johns Hopkins University. The foreword to the book was by the president of the University, Isaiah Bowman.

In this book, Monge made no secret of his violent objection to Barcroft's views. He wrote, ‘Andean Man being different from sea‐level man, his biological personality must be measured with a scale distinct from that applied to the men of the lower valleys and plains … The climatic imperatives determine and sustain an adaptive equilibrium. Ignorance of these postulates has led eminent men of science to make shocking errors of interpretation. Hence the incredible statement of Professor Barcroft, the Cambridge physiologist, who after staying three months at Cerro de Pasco (4300 m) [it was actually only one month] while emphasizing the enormous physical resistance of Andean Man, says that he is a person of impaired physical and mental powers. For our part, as early as 1928 we proved … that Professor Barcroft was himself suffering from a sub‐acute case of acute mountain sickness without realizing it.’

Monge's spirited response presumably had its basis in his intense nationalism and pride of Peru. He went on to organize an expedition to Cerro de Pasco, possibly in response to Barcroft's book, where exercise studies were carried out that emphasized the exceptional physical performance of the permanent residents (Monge, 1928). He was also the first person to describe chronic mountain sickness, which is characterized by excessive polycythaemia and is frequently referred to as Monge's disease (Monge, 1929).

However Monge's argument against Barcroft's statement is not easy to follow. He stated that Andean Man is at a disadvantage because of his low oxygen environment and therefore he should not be judged by the same criteria as is the case for lowlanders. But this is really the main point of Barcroft's assertion, that is, that because highlanders are living at a disadvantage in their low oxygen environment, they have impaired physical and mental powers.

A strategy to overcome Monge's ‘climatic aggression’ using oxygen‐enriched facilities

When Monge used the term ‘climatic aggression’ he was referring to what he saw as the inevitable hypoxia of high altitude. However with modern technology this is no longer inevitable under some conditions.

Oxygen enrichment of room air to benefit people at high altitude was first described 20 years ago (West, 1995). The principle is simple. Oxygen is generated from air using one of several techniques, the simplest being to extract it using synthetic zeolites. The oxygen then is pumped into a room or other closed space with a minimal acceptable ventilation and its concentration is monitored. There is no fire hazard because although the $P_{{\mathrm{O}}_2}$ in the room is increased, it is still far below the sea‐level value. This procedure is now being used all over the world in many high altitude settings including hotels, dormitories, offices, telescopes, mines and factories. The installation requires some electrical power to generate the oxygen but otherwise is not complicated to set up.

Oxygen enrichment of room air could play a valuable role in improving the environment of people who live at high altitude. For example consider Cerro de Pasco. Not surprisingly this has changed tremendously since Barcroft's time. Figure 4 shows a photograph taken by the expedition in 1920 of a boy said to be 10 years old carrying a load of ore weighing 18 kg. He is at the head of stairs leading to the mine 250 ft (76 m) below. This is a pitiable scene. Contrast this with Fig. 5, which shows the intensive care unit in the modern EsSalud Hospital in Cerro de Pasco. Incidentally this is reported to be at an altitude of 4380 m and have a barometric pressure of only 452 mmHg. It is easy to imagine that parts of this hospital would benefit from oxygen enrichment.

Figure 4. Cerro de Pasco in 1920 .

The boy, said to be 10 years old, is carrying a load of 18 kg of ore from the mine, which is 250 ft (76 m) below the surface. From Barcroft et al. (1923). With permission.

Figure 5. Cerro de Pasco in 2014 .

Part of the intensive care unit of the EsSalud Hospital, Cerro de Pasco. Courtesy of Dr Amilcar Tinoco Solorzano. With permission.

One example would be the nursery where newborn babies are placed after delivery. While most of these presumably cope fairly well, some may have respiratory problems. In general expectant mothers would go to a low altitude to give birth if they could, but in a remote, poor town like Cerro de Pasco this is generally impossible because of the cost. By reducing the equivalent altitude of the nursery we can expect that some babies will benefit. Another example in the same hospital might be the operating rooms. Presumably the patient is usually intubated and given an oxygen‐enriched mixture to breathe, but it is likely that the dexterity of the surgeons would benefit by in effect being transported to a lower simulated altitude.

Other facilities in Cerro de Pasco would presumably also benefit from oxygen enrichment. An example is the enormous open‐cut mine where critical decisions must be made about logistics from time to time. An example would be in the dispatcher's office where the movement of mechanical shovels and enormous trucks is planned. Decision making is likely to be much more accurate at a simulated lower altitude. The same is true of meetings of the board of directors where strategy is discussed. Also some school rooms could presumably benefit.

Apart from its possible use for permanent residents at high altitude, oxygen enrichment has been shown to be very valuable for newcomers and sojourners at high altitude. One place where this is particularly true is the Chajnantor Plateau in north Chile, which is at an altitude of 5000 m and is the site of a number of telescopes including the enormous ALMA radio telescope. Although much of the observing is done at a lower altitude with the information being transmitted by optical cable, there is always a need for engineers and other support workers at the site. If they are indoors they can benefit from oxygen enrichment of the room air, while if they go outside to service the more than 60 antennas, they can use portable oxygen equipment with nasal cannulas.

In conclusion, Barcroft's famous assertion that people at high altitude have impaired physical and mental powers has proved to be correct. Monge's contention that this is caused by ‘climatic aggression’, by which he means hypoxia, is also true. However, with modern technology much can be done to battle the aggression and improve the conditions for people who find themselves at high altitude.

Additional information

Competing interests

None declared.

Biography

John B. West MD PhD is a professor of physiology and medicine at the University of California San Diego. He was born in Adelaide, spent 15 years in London at the Royal Postgraduate Medical School, and has been at UCSD since 1969. He was a member of Sir Edmund Hillary's Silver Hut Expedition to high altitude in 1960, and led the American Medical Research Expedition to Everest in 1981. He has worked extensively with NASA and was Principal Investigator on several SpaceLab experiments. He has written textbooks on respiratory physiology and developed a teaching series on YouTube.