Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PL005

Prize Lectures

From mountains to the bedside: Lessons learnt from Everest

D. Martin1,2

1. , Critical Care Unit, Royal Free Hospital, University College London Division of Surgery and Interventional Science, London, London, United Kingdom. 2. Institute of Sport Exercise and Health, UCL Centre for Altitude Space and Extreme Environment Medicine, London, United Kingdom.

Humans are extremely resilient organisms and have successfully adapted to inhabiting and exploring almost every corner of the planet and out beyond its vicinity. Numerous environmental conditions threaten human survival, including heat, cold, microgravity and through a reduction in atmospheric pressure, the lack of oxygen experienced on ascent to high altitude. As we began to explore the mountainous regions of the world, one of the greatest barriers to success was the thin air at great heights which made the smallest of tasks feel like a Herculean effort. Hand in hand with the desire to conquer the Earth's surface came a wish to work out what caused this overwhelming exhaustion. We now know that it is due to the progressive decline in oxygen that is experienced as one ascends and understanding how the body alters and acclimatises to this lack of oxygen has fascinated physiologists for decades. Sir Joseph Barcroft, Griffith Pugh, John West and Jim Milledge are just a few names that have contributed significantly to this field over the last century. Disease can lead to internal physiological challenges, arguably in a manner comparable to those that our external environment can generate. Hospitalisation is a significant threshold in the development of any disease, representing deterioration that requires focused investigations and interventions. Failure to respond to treatment and further deterioration can result in a patient requiring admission to an intensive care unit (ICU) to support failing organs and provide complex specialist interventions to the most severely compromised patients in the hospital. Patients in an ICU have a wide range of underlying conditions and therefore present a great heterogeneity of both pathology and treatments. One factor that is common amongst these patients is a lack of oxygen (hypoxia), much like that seen in those at high altitude; the commonest drug given to patients on ICU is therefore oxygen. Despite this, we know surprisingly little about how this lack of oxygen affects our patients, whether they are able to adapt to it and how to optimise the use of oxygen as a therapeutic agent. Research at high altitude may offer an opportunity to study the effect of hypoxia in a more scientifically controlled manner than on an ICU and act as an alternative to animal models of disease. Using a natural model of environmental hypoxia and measuring the responses of healthy volunteers to a graded exposure to high altitude allows us to focus on pertinent physiological pathways. In turn this creates a platform from which we can then return to the bedside and evaluate important mechanisms identified at altitude in critically ill patients. Through a series of expeditions to high altitude we have studied numerous components of human physiological responses to altitude and are building a picture of a successfully adapted phenotype. Our approach has been to tackle questions at a systemic (whole body), organ, tissue and cellular level, to give us the most comprehensive answers that are feasible from an austere environment. Studying individuals living at sea level and those who have lived at altitude for generations provides us with the ability to differentiate between immediate and long-term strategies to tolerate hypoxia. Our findings may lead to the discovery of novel ways to tackle hypoxia in critically ill patients. Other extreme environmental conditions may also enrich our understanding of human physiology and lead to clinical benefits that would otherwise not have been discovered. The close relationship between exploration of the universe in which we live and how we change as organisms whilst pushing the boundaries of our physiology may be crucial to the survival of our species.

Where applicable, experiments conform with Society ethical requirements