Five years on from the first Cauldwell Xtreme Everest research expedition, a second is planned, this time concentrating on Sherpas. Research leader Dr Edward Gilbert explains how it will extend our understanding of high-altitude physiology and why that could improve survival rates in hospital.
At the start of the millennium, the Centre of Altitude, Space and Extreme Environment Medicine (CASE) was established at University College London. It was the brainchild of a number of doctors working in London, fuelled by a shared passion for human physiology and the extreme environment. Their aspirations for the new centre followed in the long tradition of Anglophone high-altitude research.
Working in intensive care units (ICU), they came to realise that irrespective of the initial cause of a patient’s illness, one feature common to nearly all was lack of oxygen in their blood. One in a thousand people are admitted to an ICU, and 20 percent of them die before discharge. Current medical treatments are evidently limited and inadequate.
Research and drug trials are obvious requirements before new treatment regimes are introduced. But patients in ICU are often too ill to be entered into these studies. Treatment advances can be thwarted or slow to develop.
It was this Catch-22 that led the pioneers of CASE to develop the paradigm now central to all our research: if physiological responses to low environmental levels of oxygen are comparable to those responses witnessed in critically ill patients, then by studying healthy individuals exposed to hypoxia at high altitude, we can learn important lessons for patients in ICU.
By seeing who copes well or badly with the ‘environmental insult’ of hypoxia, and then by describing and duplicating the beneficial adaptive mechanism, we might ultimately develop new treatments for the critically ill.
Caudwell Xtreme Everest
This hypothesis of mountainside to bedside inspired CASE to organise Caudwell Xtreme Everest (CXE), named after its major donor, mobile phone entrepreneur John Caudwell. CXE was the largest ever high-altitude expedition with more than a million catalogued items requiring shipment to Nepal.
Over 60 medical doctors and researchers staffed laboratories in London, Kathmandu (1300m) , Namche Bazaar (3500m), Pheriche (4300m), Everest Base Camp (5300m) and onwards up the mountain to the Western Cwm (6400m) and the South Col (7950m). During the spring of 2007, 240 trekking guinea pigs gave up their Easter holiday to science, walking from Kathmandu to EBC in 15 days.
As they ascended, researchers took their blood, stuck them on exercise bikes, analysed pupil reaction time and measured their brain blood flow. CASE were able to see what was happening to the trekkers as the gained altitude, and identify those who coped well and those who didn’t.
Not content to sit and watch, a team of doctors with exercise bikes and test tubes in tow, climbed to the summit of Everest and performed tests and took blood samples from each other at the South Col.
Xtreme Everest 2
Now CASE is returning to Everest, following further high-altitude and chamber-based studies. This time our attention will be observing what happens to those who work so hard on Everest, those peerless high-altitude dwellers, the Sherpas.
Evolved over thousands of years to cope with low oxygen levels, little is known about their physiology and how it differs from other groups. Several papers have been published recently about the genetics of Tibetan groups like Sherpas, but less has been done on the downstream effects of these variants.
We will do a large-scale study comparing Sherpas and lowlanders, encompassing over 60 individual studies looking at them from head to toe. While other research on Tibetan groups has looked at one or two physiological parameters, we want to look at all of them.
For example, if we find Sherpas’ microcirculatory blood flow is far better than ours, we will want to find out what molecules allow this to happen. We’ll be doing some work using muscle biopsies to look at oxygen usage in mitochondria.
Do Sherpas use oxygen more efficiently? This seems to be the implication of studies done so far. Unlike us, Sherpas don’t respond to high altitude by increasing haemoglobin – red blood cells – to increase oxygen delivery around the body.
Once again, we’ll be setting up laboratories in London, Kathmandu and Khumbu to study lowlanders and Sherpas alongside each other. With the knowledge gained of Tibetan physiology, we hope to see whether emulating these biological changes in severely unwell patients in the hospital setting will improve survival rates.