Brief history of the medical and non-medical use of amphetamine-like psychostimulants.

The alkaloid ephedrine derived from Ephedra vulgaris is at the origin of psychostimulant-drugs as amphetamine. These drugs have been principally utilized for medical treatments in the past, while their utilization has been largely reduced from the 1970s when the high risk of addiction and abuse has been recognized. The first reported treatments were as anti-asthmatics and to contrast narcolepsy until their recreational stimulant and anorexic effects were reported. Benzedrine and Pervitin use were of great importance during the Second World War due to their abundant utilization among military troops. Nowadays the use of selective amphetamine-like drugs is limited to ADHD treatment.

Alexander von Humboldt (1769-1859): early high-altitude explorer and renowned plant naturalist.

Alexander von Humboldt (1769-1859) was one of the most distinguished German scientists of the late 18th and early 19th centuries. His fame came chiefly from his extensive explorations in South America and his eminence as a plant naturalist. He attempted to climb the inactive volcano Chimborazo in Ecuador, which was thought to be the highest mountain in the world at the time, and he reached an altitude of about 5,543 m, which was a record height for humans. During the climb, he had typical symptoms of acute mountain sickness, which he correctly attributed to the low level of oxygen, and he was apparently the first person to make this connection. His ability as a naturalist enabled him to recognize the effect of high altitude on the distribution of plants, and by comparing his observations on Chimborazo with those in the European Alps and elsewhere, he inferred that the deleterious effects of high altitude were universal. During his return trip to Europe, he called on President Thomas Jefferson in Washington, where he was given a warm reception, and discussed conservation issues. He then returned to Paris, where he produced 29 volumes over a period of 31 years describing his travels. Here the effects of high altitude on the distribution of plants compared with animals are briefly reviewed. Following Humboldt's death in 1859, there was extensive coverage of his contributions, but curiously, his fame has diminished over the years, and inexplicably, he now has a lower profile in North America.

"The Great Silk Road" and the First Description of Hypoxia.

The first written reports about the effect of high-altitude air on the human organism in Ancient China (the 30s BC) and in South America during the conquest (late XVI century) are discussed in this paper.

Early history of high-altitude physiology.

High-altitude physiology can be said to have begun in 1644 when Torricelli described the first mercury barometer and wrote the immortal words "We live submerged at the bottom of an ocean of the element air." Interestingly, the notion of atmospheric pressure had eluded his teacher, the great Galileo. Blaise Pascal was responsible for describing the fall in pressure with increasing altitude, and Otto von Guericke gave a dramatic demonstration of the enormous force that could be developed by atmospheric pressure. Robert Boyle learned of Guericke's experiment and, with Robert Hooke, constructed the first air pump that allowed small animals to be exposed to a low pressure. Hooke also constructed a small low-pressure chamber and exposed himself to a simulated altitude of about 2400 meters. With the advent of ballooning, humans were rapidly exposed to very low pressures, sometimes with tragic results. For example, the French balloon, Zénith, rose to over 8000 m, and two of the three aeronauts succumbed to the hypoxia. Paul Bert was the first person to clearly state that the deleterious effects of high altitude were caused by the low partial pressure of oxygen (PO2), and later research was accelerated by high-altitude stations and expeditions to high altitude.

Stanhope Speer, Physician and Alpinist: In 1853, First to Describe Mountain Sickness?

In 1853, Stanhope Templeman Speer published a two-part paper in The Association Medical Journal on Mountain Sickness. Speer was a physician who had worked at the Brompton Hospital for Chest Diseases in London and had been Professor of Medicine in Dublin. He was also an Alpine climber and had made the first ascent of one of the Wetterhorn peaks. His article ran to ten and a half pages in the Journal and to 50 pages in a reprint. It consists of anecdotal accounts of symptoms suffered at altitude from the literature and from his own experiences in the European Alps. He asks three pertinent questions. Is there a condition of mountain sickness? Are these symptoms felt by all persons alike and at the same height? What are the causes, and whence the explanation of such phenomena? In the course of the article, he answers the first two questions but, like us, 162 years later, is unable to answer the third. This article seeks to present Speer's original work and such facts about his life as I have been able to discover.

Dull Brains, Mountaineers, and Mosso: Hypoxic Words from on High.

Dull and hypoxic brains have been a frequent subject in the medical and mountaineering literature. Deterioration of cognitive and other neurological function occurs at high altitude, with or without high altitude cerebral edema. This historical essay explores a 2014 first-ever English translation of cerebral blood flow studies by nineteenth century physiologist Angelo Mosso. Some of the medical history and physiology of brain function is discussed, but much of the style focuses on quotations from the writings of mountaineers and mountaineering physicians to provide color commentary about dull brains at high altitude.

Dilated hearts at high altitude: words from on high.

From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary.

Extreme altitude: words from on high.

Medical science has its own objective language for describing the effects of high altitude. Mountaineers' words and metaphors tell the story with subjectivity and feeling. This essay will include only limited physiology about lowlanders and high altitude. Instead, the focus will be literary, using the quotations of 20th-century mountaineers and mountaineer physicians to provide color commentary about the hardship. These are Words From on High.

Joseph Barcroft's studies of high-altitude physiology.

Joseph Barcroft (1872-1947) was an eminent British physiologist who made contributions to many areas. Some of his studies at high altitude and related topics are reviewed here. In a remarkable experiment he spent 6 days in a small sealed room while the oxygen concentration of the air gradually fell, simulating an ascent to an altitude of nearly 5,500 m. The study was prompted by earlier reports by J. S. Haldane that the lung secreted oxygen at high altitude. Barcroft tested this by having blood removed from an exposed radial artery during both rest and exercise. No evidence for oxygen secretion was found, and the combination of 6 days incarceration and the loss of an artery was heroic. To obtain more data, Barcroft organized an expedition to Cerro de Pasco, Peru, altitude 4,300 m, that included investigators from both Cambridge, UK and Harvard. Again oxygen secretion was ruled out. The protocol included neuropsychometric measurements, and Barcroft famously concluded that all dwellers at high altitude are persons of impaired physical and mental powers, an assertion that has been hotly debated. Another colorful experiment in a low-pressure chamber involved reducing the pressure below that at the summit of Mt. Everest but giving the subjects 100% oxygen to breathe while exercising as a climber would on Everest. The conclusion was that it would be possible to reach the summit while breathing 100% oxygen. Barcroft was exceptional for his self-experimentation under hazardous conditions.

Denis Jourdanet (1815-1892) and the early recognition of the role of hypoxia at high altitude.

Denis Jourdanet (1815-1892) was a French physician who spent many years in Mexico studying the effects of high altitude. He was a major benefactor of Paul Bert (1833-1886), who is often called the father of high-altitude physiology because his book La pression barométrique was the first clear statement that the harmful effects of high altitude are caused by the low partial pressure of oxygen. However, Bert's writings make it clear that the first recognition of the critical role of hypoxia at high altitude should be credited to Jourdanet. Jourdanet noted that some of his patients at high altitude had features that are typical of anemia at sea level, including rapid pulse, dizziness, and occasional fainting spells. These symptoms were correctly attributed to the low oxygen level in the blood and he coined the terms "anoxyhémie" and "anémie barométrique" to draw a parallel between the effects of high altitude on the one hand and anemia at sea level on the other. He also studied the relations between barometric pressure and altitude, and the characteristics of the native populations in Mexico at different altitudes. Jourdanet believed that patients with various diseases including pulmonary tuberculosis were improved if they went to altitudes above 2,000 m. This led him to recommend "aérothérapie" in which these patients were treated in low-pressure chambers. Little has been written about Jourdanet, and his work deserves to be better known.

Mountain research and rescue on Denali: a short history from the 1980s to the present.

Alaska's Denali (Mt. McKinley), 6194 m, is the highest and perhaps most celebrated peak on the North American continent. The cold and stormy nature of this mountain just 3° of latitude south of the Arctic Circle enhances its legend as a challenging peak. It has been the desired objective of over 1000 summit aspirants per climbing season for the last 20 years. As mountaineering traffic on the peak increased in the 1960s and 1970s, an increase in deaths and helicopter evacuations followed suit. These were largely owing to altitude illness, cold injuries, and trauma. By the late 1970s and early 1980s, the U.S. National Park Service (NPS) began exploring potential solutions regarding the problems with rescue scenarios in remote and hostile surroundings. The NPS eventually placed a team equipped with communications and medical supplies high on the mountain to remedy the problem. This seasonal high altitude camp, established in 1982, carried out clinical research, preventive education, and rescue work. Although this operation has undergone substantial changes since 1982, it continues to serve Denali climbers each season and has likely reduced the frequency of serious accidents, death, and helicopter rescues. In addition, a parallel increase in NPS infrastructure, medical research, and mountain rescue on this peak has contributed to an increased benefit for climbers and others, which has served (and continues to serve) a wide range of interests, from the safety concerns of mountaineers to high altitude-related scientific discoveries advantageous to the scientific community.