Experiments of nature and within species comparative physiology.

This graphical review highlights a focused application of a key principle ('Krogh Principle') identified by Nobel-prize winning physiologist Professor August Krogh (1874-1949) that states "for many problems there is an animal on which it can be most conveniently studied". We apply the Krogh Principle to human physiology by proposing that "for many problems there is a unique group of humans on which it can be most conveniently studied". As such, we present 5 unique human case studies. Case 1 discusses whether signals from exercising muscles cause blood pressure to rise using a patient with a spinal cord lesion. Case 2 investigates the role of the sympathetic nervous system in the blood pressure response to exercise using patients who have undergone sympathectomy for hypertension. Case 3 asks whether increases in blood lactate are necessary for the non-linear increase in breathing with heavy exercise using patients with McArdle's disease. Case 4 applies fundamental scaling principles from comparative physiology to elite athletes to investigate the role of body size on maximal aerobic capacity. Finally, Case 5 describes our recent work that investigates whether a left shift in the oxygen hemoglobin dissociation curve can facilitate hypoxic exercise using patients with left-shifted hemoglobinopathies. In summary, we have expanded the inter-species message of the August Krogh Principle and highlighted the need to search for odd examples and experiments of nature. In this context, observations from unusual humans are a source of insights into physiology, which may be translated into therapeutic approaches for disease.