Conquistadores and cot death

This essay was written by Marianne Neary and was first published in the 2010 Mill Hill Essays. An updated version was published in the Mill Hill Essays anthology. 

When Francisco Pizarro and his Spanish army arrived at the borders of the Inca Empire in 1528, they faced some of the most mountainous terrain on earth. They were not viracocha cuna, or ‘gods’, as the Incas had initially mistaken them for; they had come to forge the collapse of one of the most prized empires in the world.

Francisco Pizarro
Francisco Pizarro. The Spanish Conquistador and conqueror of the Incan Empire

The Conquistadores pursued the Incas higher and higher into their lofty abode. The Incas were not retreating, however. Well aware of the effects of altitude on lowlanders, theirs was a cunning trick leading the Spanish into the gasping jaws of Mother Nature. Alas, no great battle is without a struggle and, despite the military prestige of the Conquistadores, this was no exception. Only in 1545 did they eventually establish the city of Potosi; at an elevation of 4090m it was the world’s highest city. However, Potosi was never more than a frontier town: due to the altitude Spanish babies and cattle all died at birth. The only hope of survival was for pregnant women and animals to descend to the lowlands in order to give birth and rear their young for the first year of life.

Five hundred years later, this same dilemma haunts our earthly heights, from the Han Chinese population of Tibet to the cattle ranchers of the Rocky Mountains. Joseph Neary, a vet in the Rocky Mountain National Park, has observed that, unlike those species that have evolved to live at high altitude such as llamas and yaks, cattle can develop a condition known as High Mountain Disease (HMD). 75% of cattle loss to HMD occurs in animals less than 2 years old.

We do not have a scientific explanation of these observations, though we do know that a major challenge of living at altitude is the lack of oxygen. Since an unborn baby or calf is subject to similar conditions of low oxygen in the womb, it is a puzzle why they should struggle at high altitude. The answer to this conundrum may shed light not just on the problem of fatalities at birth but also on conditions such as Sudden Infant Death Syndrome or ‘cot death’.

Panorama of Potosi, Bolivia
Panorama of Potosi, Bolivia.
This picture was taken and modified by Martin St-Amant. This image is distributed under the Creative Commons Attribution 3.0 Unported License. http://bit.ly/bLeg1M

Getting to the heart of the matter may lead us just there. Our heart clocks up a whopping 100,000 beats every day and consumes a great deal of energy in the process. To generate this energy the heart has a choice of fuels: fat, which provides the most energy, or sugar, which generates less energy but doesn’t guzzle as much oxygen in the process. In the normal adult heart, fat is the fuel of choice. Before we were born however, our hearts used sugar; this makes sense considering the relative paucity of oxygen in the womb. Following this logic it is no surprise that the switch of fuel, back to sugar, happens within a few hours of birth, when our heart has to suddenly adapt to deal with larger pressures and energy demands.

We hypothesise that if this switchover in fuel does not occur, the heart cannot meet the increased demands and fails to cope: this proves fatal. What could happen to prevent this switch occurring? Insights gained from the Spanish conquest suggest that increased oxygen availability could be the trigger for the switch. So when oxygen concentration is as low outside the womb as it is inside, as it is at high altitude, problems arise.

The fact that Spanish infants had to be raised in the lowlands for a whole year before returning to altitude further suggests that the switch remains unstable and liable to change in early life. This may echo a poignant truth for cot death, which occurs in the same time frame. Looking at the risk factors for cot death, you see that most of them can point to low oxygen: prone sleeping position, maternal smoking, bed sharing and head covering.

The link between metabolic pathways, oxygen and infant mortality
The link between metabolic pathways, oxygen and infant mortality

Exploring this further, we have found that immediately after birth a key fat-burning metabolic pathway is turned on in the heart and this pathway turns out to be activated by increased oxygen. Yet how come the Inca babies survived? A scientific report published in May this year revealed that populations native to high altitudes have subtle variations in two genes. Adding support to the theory, one gene relates to oxygen sensing and is the same gene that is found to vary in activity at birth; the other induces the same fat-burning pathway we described above.

The next steps are now to see whether artificially blocking portions of this pathway and interfering with the oxygen sensing machinery prevents the fuel switchover.

If the theory is correct, maintaining normal oxygen levels could spare the heartache of cot death. Simply ensuring adequate ventilation in an infant’s room and cot may achieve this. Dr Joseph Neary, from the Rocky Mountain National Park reports that “One ranch I visit gives oxygen to calves after they are born at high altitude. So far, this has increased the proportion of calves surviving to weaning”.

Whether this translates into human physiology remains, for the moment, ‘up in the air’.

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