JUNG-MO is a Tibetan yak herder. In the summer she lives with one of her sons at altitudes of up to 4800 metres on the eastern slopes of Everest. They share a tent woven from yak hair and have few possessions beyond a thermos to keep their salt tea hot and a photo of the Dalai Lama. Life in the mountains is harsh, but it’s surprising how many people make their homes there. Worldwide, around 140 million people live above 2500 metres, and that’s set to rise as resident populations grow and more people move into mountainous areas.
It’s a testament to human adaptability that we can survive in this alien environment. Despite evolving in the African lowlands we have the resourcefulness to cope with most of the challenges imposed by a life at altitude. Human ingenuity allows us to overcome extremes in temperature, a natural scarcity of resources such as wood and food, and exposure to damaging solar radiation. But at high altitude one challenge dwarfs all others: lack of oxygen. Jung-mo and her neighbours, for example, breathe air that contains little more than half the oxygen of that at sea level.
How can humans survive when deprived of this essential life-giving gas? How we adapt depends on our ancestry. Native lowlanders who’ve moved to the mountains show a range of anatomical and metabolic changes that help them get by. People whose families have lived at altitude for generations, however, have evolved to cope with the low oxygen levels. Their genes give them a head-start for mountain life. And, intriguingly, women seem to be better adapted to the high life than men.
Advertisement
The northern Tibetan Plateau is bleak, rocky and arid. It looks uninhabitable, yet stone tools found here in the 1980s identify it as the oldest known high-altitude settlement. The most ancient of these artefacts suggest that humans were living here at least 50,000 years ago.
This is one of two regions that Lorna G. Moore of the University of Colorado ÎçŇą¸ŁŔű1000ĽŻşĎ Sciences Center has visited to study the relationships between altitude, evolution and health. The other is the Andes which is unlikely to have been permanently settled for longer than about 6000 years, because people couldn’t have survived there before they learned how to cultivate potatoes and grains, and domesticate llamas and alpacas.
By comparing native Himalayan and Andean dwellers with people whose ancestors moved to the highlands relatively recently, Moore and her colleagues are building a picture of human evolution in action. Moore, fellow anthropologist Stacy Zamudio, who has just moved from Colorado to the New Jersey Medical School in Newark, and University of Colorado paediatrician Susan Niermeyer have focused on pregnancy and childbirth. Zamudio points out that from an evolutionary perspective these are the critical times. “The greatest mortality risk occurs in utero,” she says. “Natural selection takes place very early in pregnancy.” And in the developing world, more women die during pregnancy than at any other time. So, when it comes to adapting to altitude, these are the two most crucial times.
Less oxygen in the air means lower oxygen levels in the blood, and fetuses are particularly susceptible. One way the bodies of pregnant women compensate is to temporarily increase the amount of blood oxygen by upping haemoglobin levels and by increasing the amount of oxygen each haemoglobin molecule carries – its “oxygen saturation”. This seems to be the easiest short-term option: it’s seen in native lowlanders such as the Han Chinese, who have been encouraged to move to the Tibetan Plateau in recent decades, and in people who have settled in the American Rocky Mountains, where permanent habitation dates back just 150 years. It allows pregnant women to achieve oxygen levels in their blood comparable with those found in people living at sea level. But it’s clear their unborn babies still aren’t getting enough oxygen and other essential nutrients, because their average birthweight is reduced by 100 grams for every 1000-metre gain in altitude.
For native highlanders, however, there must be a more successful adaptation, because the babies of Tibetan women are substantially heavier at birth than those of other high-altitude mothers. Moore and Zamudio discovered that, surprisingly, pregnant Tibetans have lower concentrations of haemoglobin and arterial oxygen than other mothers living at altitude. It seems odd, but the researchers suspect Tibetan mothers-to-be do have high blood oxygen levels, it just looks like they don’t because they produced more blood altogether. This, argues Moore, would allow them to redistribute blood flow to the pelvis and to the uterine artery in particular.
She’s found that Bolivian women, whose ancestors have lived in the mountains for 6000 years or more, undergo a similar but less dramatic physiological change during pregnancy. She believes there’s a “gradient” between the amount of change and the time your ancestors have spent at altitude. This suggests a gradual and ongoing adaptation.
In the womb, a fetus is buffered from the outside world by its mother. But once born, a mountain baby must cope with the rarefied atmosphere for itself. The first hurdle is to start breathing. Niermeyer and others have found that, here again, babies with a long pedigree of highland living have the advantage. Comparisons between native Tibetans and Han Chinese newcomers living at the same altitude show that babies born to the immigrants take longer to start breathing air efficiently after birth. What’s more, their oxygen saturation levels are permanently lower than those of native Tibetans. At four months, saturation has stabilised at around 76 per cent in the Han, compared with 86 per cent in Tibetans. In countries where babies are born at sea level the figure is around 98 per cent.
Oxygen saturation level probably has a permanent effect on the physical fitness of people living at altitude, says Moore. But, despite much research, the causes of poor exercise performance at altitude remain illusive. What is known is that, on average, there’s an 11 per cent reduction in VO2 max, a measure of maximum exercise capacity, for every 1000-metre increase in height. What’s also clear – as any mountaineer who has climbed with a Sherpa knows – is that acclimatised newcomers suffer most and native highlanders least. Indeed, populations that have been mountain dwellers for the longest, such as native Tibetans and Bolivians, have VO2 max measurements similar to those found in people living at sea level.
Overall, genetics seems to account for about 25 per cent of the variability in physical fitness between people at altitude. Developmental influences contribute a similar amount and lifestyle makes up the rest. One of the most obvious physical adaptations is a larger, deeper chest with greater lung capacity. Whatever your ancestry, this will develop simply as a result of growing up at altitude. Other adaptations are a higher breathing rate and more efficient lungs, which together increase the amount of oxygen in the blood. Once again, there seems to be a gradient, with people whose ancestors have lived at altitude for longest having the highest oxygen levels.
Tibetans’ secret weapon
But Moore and others suspect that the secret weapon of Tibetans and other native Himalayan peoples is their blood vessels. One indication of this is that they have a similar blood pressure in their pulmonary artery to that of people at sea level. Moore explains that in a fetus the pulmonary artery, which carries blood from the heart to the lungs, has a thick muscle wall but that this normally thins after birth when a baby starts breathing air. When native lowlanders live at high altitude their pulmonary artery reverts to the fetal structure, raising the blood pressure within it. But not Tibetans – their arterial walls remain thinner, so their pulmonary artery pressure is low. With less arterial resistance their hearts can pump larger quantities of blood to the lungs during exercise. It’s exactly what you see in other animals adapted to high altitude, such as llamas and yaks, comments Moore.
Such physiological adaptations also seem to guard against chronic mountain sickness. CMS is a protracted version of acute mountain sickness (see “Indiscriminate attacker”). People may live for decades with the symptoms, which include facial oedema, headaches, dizziness, fatigue, loss of memory and appetite, and insomnia. It can strike from adolescence onward and seems to be a major killer, although there have been no studies of death rates. CMS is, arguably, the ultimate sign of a failure to adapt to altitude – which makes its prevalence instructive.
Overall rates are poorly documented but, not surprisingly, CMS is more common among migrants to high altitude than natives. For example, it affects 10 times as many Han Chinese as native Tibetans living at the same elevation. It is also more common among peoples native to the Andes than to native Tibetans, suggesting that resistance has evolved over time. And, intriguingly, women seem to be less susceptible than men. “Men can develop CMS as early as age 30,” says Zamudio, “whereas women tend not to develop it until they are post-menopausal – and even then, at lower rates than men.” She and Moore suspected this might be because women need to be better adapted to cope with limited oxygen to survive pregnancy and childbirth. But recent findings suggest it’s not as simple as that. “On the oxygen uptake side of things, women largely resemble men,” says Moore.
They may not have the edge here, but the suspicion that women are better able to cope at altitude is borne out in studies by Charles Fulco from the US Army Research Institute of Environmental Medicine in Massachusetts. In several experiments on people living at sea level he found that women’s muscles have about twice the endurance of men’s: when tested with a weight proportional to their muscle mass, women can continue exercising for twice as long. What’s more, women’s performance at altitude remained similar to that at sea level, while men’s endurance dropped by an average of 25 per cent. Fulco suspects that this may be because, at the cellular level, women replenish their energy stores during rest periods more quickly than men, providing their muscles with a ready supply of fuel to keep on contracting.
More evidence that women’s metabolism differs from men’s comes from studies by Barry Braun from the University of Massachusetts, Amherst, who has been looking at the foods we burn during exercise. The received wisdom is that as we climb to altitude our bodies perform best if we eat mostly carbohydrates. But Braun realised that this finding came only from studies of men, so he decided to look at what happens in women. He found that women don’t seem to switch to using more carbohydrate – they may even use more fat. In other words, women draw on a more energy-rich supply of nutrients. This natural physiological advantage could have given women a head-start when it came to adapting to life at altitude.
While it’s intriguing to unravel the mysteries of how humans cope when pushed to the edge, research in mountain regions is fraught with difficulty – not least because of local political tensions. But while work has barely begun, the evolutionary process itself could be coming to an end. Zamudio points out that advances in medical technology are already undermining the power of natural selection, which in the past has weeded out those mothers and babies unable to cope with life at altitude. “You won’t find the evolution that we’re speaking of in the US or anywhere where there are tertiary neonatal intensive care units,” she says. Such medical technologies seem far removed from Jung-mo as she herds her yaks on the flanks of Everest, but one day they will be available to all mountain dwellers. Then it won’t just be the fittest and best adapted who can survive. Life at altitude will be a lot easier for everyone.
Indiscriminate attacker
Acute mountain sickness affects over half of all lowlanders who spend more than a few hours above 3500 metres. It makes little difference whether you’re an ultra-fit climber with dozens of Himalayan summits under your belt or a couch potato who has never climbed higher than the top shelf of the larder. What’s more, on one visit to altitude you may be fine, but on the next you could be struck down with the headaches, nausea, disorientation and lethargy that are the hallmarks of AMS. Why is it so unpredictable?
The jury is still out, but theories abound. “The received wisdom is that fitness is irrelevant to developing mountain sickness,” says Jo Bradwell from Birmingham University. But he doesn’t buy that. And this summer he and his team took an exercise bike up a mountain in the Bolivian Andes to test their paradoxical theory that fitter people are more susceptible.
The root cause of AMS is a lack of oxygen in the blood – hypoxia – which somehow triggers fluid to leak from blood vessels into the brain. The body normally tries to compensate for hypoxia by stepping up the heart rate and breathing rate. But at altitude this can be counterproductive because the faster blood flow through the lungs, the less time it has to become fully oxygenated. Bradwell suspects that the fitter you are, the more likely it is this will happen when you exercise at altitude. That’s because fit people tend to have bigger muscles, which require more oxygen. That leads to more severe hypoxia and a stronger attempt by the body to compensate.
And that’s where the exercise bike comes in. Bradwell and his team had 20 climbers furiously pedalling away at 3600, 4700 and 5250 metres on a mountain called Huayna Potosi near La Paz. The researchers measured the oxygen in their brains at varying levels of exertion. They are still analysing the results, but Bradwell is upbeat. “I suspect that the fitter individuals will be the ones with lower brain-blood oxygen counts,” he says.
“Exertion does make everything worse,” agrees Charles Houston from the University of Vermont in Burlington. But after two decades studying AMS, he believes that the best place to look for differences in susceptibility is our genes. “Of the several dozen influences that affect us at altitude, I think many of them will turn out to have a genetic basis,” he says.
Some recent research supports Houston’s prediction. In July this year, Masayuki Hanaoka from the Shinshu University School of Medicine in Matsumoto, Japan, announced a possible genetic link to high-altitude pulmonary oedema (HAPE) – a potentially fatal side effect of hypoxia in which fluid builds up in the lung. He found that two variations in a gene called eNOS occur more often in people who suffered HAPE. They are bad news for anyone wanting to climb to altitude, according to Nicholas Morrell from Cambridge University, who has identified a similar genetic variation in the people of mountainous Kyrgyzstan. “Put simply, you’re more likely to get to the summit of Everest if you don’t have these variations.”
But Houston believes that psychology may be almost as important as physiology. “A lot of tolerance to altitude is due to motivation,” he says. “If you expect to get sick at altitude then you probably will.”