High life is in the blood

March 16, 2001

How do communities in the Andes and Tibet cope with living at such high altitudes? Cynthia Beall believes it is a question of evolution. Steve Farrar reports.

It was not an ideal start. En route to the nomad's camp, some 4,000m above sea level on the Tibetan plateau, the truck got stuck in ice while crossing a stream. Then the driver got lost amid the unfamiliar mountainous terrain. Far later than intended, the truck's headlights scooped three or four black yak's wool tents from the darkness of the night. The government official who had guided (and misguided) the party thus far leapt from the cabin, strode over to the first tent and found the nomads' bewildered headman. "Don't lie to them," he advised his passengers, before jumping back into the truck and starting the two-day journey home.

As the engine's rumble faded into silence, Cynthia Beall, a biological anthropologist from Case Western Reserve University in the United States, found herself among people who had never seen a westerner. She pondered the challenges ahead. Beall was no stranger to working with isolated communities in remote climes - before this pioneering expedition she had spent time working high in the Andes of Bolivia and Peru. Also, she was not alone. Accompanying Beall was Case Western colleague Melvyn Goldstein, an internationally respected Tibetologist whose command of the language is allegedly so good it can prompt old women to weep in the streets, and an enthusiastic and resourceful assistant from the Tibetan capital Lhasa.

Beall had already braved the bureaucracy that an American academic must face to gain access to the interior of Tibet's autonomous region, as well as the trying journey to reach this elevated camp. Now, in a bid to understand how these nomads were able to live and work at such altitudes, she would seek answers in their lifestyle and blood.

Those of us whose ancestors originated from less lofty regions find it difficult to function at such heights. At 4,000m, where the volume of air has just 63 per cent of the oxygen molecules that it has at sea level, the least bit of exertion -physical work, carrying loads or walking up hill - leaves most of us gasping for breath. Yet there are some populations who seem unaffected. Beall recalls clearing a 6,700m mountain pass with a group of Tibetans. While she was breathing heavily with the strain, her companions were able to chase after a fleeing yak. It was all Beall could manage just to stand and watch.

Not that lowlanders are completely helpless in the face of such conditions. Our bodies have ways to respond to the challenge posed by low levels of oxygen - known as hypoxia or hypoxic stress - such as automatically increasing the depth and rate of our breathing, even when we are at rest. This boosts the amount of oxygen coming into our lungs and hence into our blood stream. But it is a costly way of overcoming a problem usually encountered for only relatively brief periods. Therefore, after some days our breathing falls back towards normal. In the meantime, the concentration of the red pigment haemoglobin, that carries oxygen to power the body's metabolism, greatly increases to compensate. Nevertheless, we never fully adapt and we are always at a disadvantage at such heights.

Not so for the Tibetans and their South American counterparts in the Andes, the Aymara and Quechua. So how do they cope? The answer lies in what Beall describes as "a natural experiment in evolution" that has conveniently occurred twice. The two populations have lived at high altitudes for thousands of years. Carbon dating places people in the Andes at least 11,000 years ago, while the discovery of crude stone tools on the Tibetan plateau could be evidence that its inhabitants have been living the high life for much longer than the 7,000-year-old carbon dates suggest. In any case, the time seems to have been sufficient for the two separate human populations to have adapted to their testing environment.

To discover the nature of those adaptations, Beall spent long periods living and working with highlanders on opposite sides of the world. So far her research has focused on four traits - how much breath people take in over the course of a minute, how this alters in response to changes in the level of oxygen, the concentration of haemoglobin in the blood, and the blood's oxygen saturation level. From this simple analysis, a startling and unexpected snapshot of evolution in action has emerged.

When she reaches an isolated mountain community, Beall works hard to build a rapport with the people she meets. Naturally, her arrival causes a stir. Beall goes to great lengths to be open and honest. "I'm very careful to explain what I do, telling Tibetan highlanders that they are famous because they can live at these altitudes without getting sick and that I am trying to find out why that is," she says. She explains her task to the head of the community and then sets up in its midst, organising her field lab in a tent, store room or village community centre. Anyone who passes by gets an explanation. Soon volunteers agree to answer questions and take part in medical examinations. Beall is particularly keen to recruit extended families as the data they generate gives her the opportunity to hunt for any genetic connections that might link them. Some refuse, especially the old and young. Dark rumours as to her true purpose can spread.

"In the Andes some people were very suspicious of giving blood as there were superstitions about blood-sucking spirits," Beall says. Yet her openness and accessibility helps win people over: "Word gets out you're a nice guy."

The highlanders of Tibet and the Andes appear to be equally well adapted to their environment - Beall's tests have not found either to be better advantaged. Yet to her surprise, the research has revealed their biology is not the same. Despite starting out with the same biochemical and genetic toolkit possessed by people the world over, the two populations have developed separate adaptations to identical stress.

The average Tibetan breathes in large volumes of air even while resting - 19.7 litres a minute for an adult male. Such quantities recall the lowlander venturing into high altitude for the first time. However, the Andean, like the acclimatised lowlander, breathes normally - 13.4 litres per minute. Similarly, depth of breathing gives a Tibetan highlander double the response of an Andean to a fall in oxygen levels.

Yet when the level of oxygen saturation of arterial haemoglobin in the blood is measured, the Tibetan averages lower than his Andean counterpart. Furthermore, the Tibetan has maybe 20 per cent lower concentrations of haemoglobin. "This finding was a real puzzle," Beall says. At the very least, this shows that you do not have to possess high concentrations of haemoglobin to live and work at high altitude.

"Natural selection has had the opportunity to act on these two populations to improve adaptation to lifelong hypoxia," Beall says. Indeed, the fingerprints of natural selection are all over the research. Tibetan heavy breathing, revealed as a strongly heritable trait, shows a great deal of variation through the population sample Beall collected. There was virtually none among the Andeans. Variation is the fuel of natural selection.

Evidence also surfaced for an important and as yet unlocated gene possessed by some but not all highland Tibetans that boosts the oxygen saturation of haemoglobin in their blood. No such variation emerged from the Andean studies, where the average level was higher still. Could it be a hint that natural selection had done its work to optimise this particular trait in the Andes yet is still in progress in Tibet? Beall is keen to carry out more tests and explore other traits that might separate the Tibetan and Andean. Yet, its true value is in providing a unique snapshot of human natural selection in all its glory -how one challenge can be met by two solutions.

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