Ketones, The Fourth Fuel: Warburg to Krebs to Veech, the 250 Year Journey to Find the Fountain of Youth

"A few days prior, Priestly had made a curious discovery: He had lit a flame in a large jar, then sealed the container until the flame burned itself out. He then place a mouse in the container and watched as it soon collapsed, apparently due to the lack of air. Had the flame consumed the life-giving gas within the ar? Inspired, Priestly then repeated the same experiment--depleting the air inside the constainer with the candle--but this time, in addition to placing the mouse inside the container, he added a mint plant from the garden, sealed the container quickly before gas could be exchanged with the outside air, and set the container in the sunlight. The mouse regained consciousness. Somehow, the combination of plant and sunlight revitalized the air and infused the mouse with life force. Additionally, he found that the flame would again burn inside the container after the plant had "restored" the air. Life, flame, and air, Priestly realized, were somehow woven together.

For today's experiment he would again use the sun. He magnified the sunlight spilling through the laboratory's only window onto a small amount of a reddish substance known as mercuric oxide. He then used his apparatus to capture the gas that was released as the mercuric oxide began to burn. For the remainder of the day Priestly would perform a series of experiments with the newly isolated gas. He began with the flame. He noticed that it burned with much more intesity when placed inside a container with the new gas. He again filled ethe container with the new gas and sealed the mouse inside. Amazingly, when comparing results to those seen with a container filled with normal air, the mouse stayed conscious four times longer. This new gas, declared Priestly , was "five or six times as good as common air."

"The feeling of it in my lungs was not sensibly different from that of common air, but I fancied that my breast felt peculiarly light and easy for some time afterwards. Who can tell but that in time, this pure air may become a fashionable article in luxury. Hitherto only two mice and myself have had the privilege of breathing it," he wrote, late in the night. 

"We must trust to nothing but facts: these are presented to us by Nature, and cannot deceive," wrote Lavoisier.

When he meticulously weighed different materials after they were combusted, h e noticed a consistent theme: they gained mass. To Lavoisier this observation implied that combustion was a process of transformation: the merger of material with air to create a n ew material. "Nothing is lost, nothing is created, everything is transformed," claimed Lavoisier. 

A year later he published a memoir on the subject unequivocally demonstrating that the new gas--that he now called oxygen--was indeed the active component in the air that reacted during combustion. The publication, in a single sweep, spectacularly demolished phlogiston theory and sparked the "chemical revolution" that ushered in modern chemistry. 

• Ketones: The Fourth Fuel by Travis Christofferson

"In ancient Egypt it was thought that only some sort of supernatural energy source could power the living. The Roman physician Galen claimed that 'innate heat' and 'spiritedness' were the 'vital forces' created by the 'pneuma' that was extracted from inhaled air in the lungs. The vitalists claimed that living organisms were imbued with a mystical force that existed on a higher plane that transcended the realm of physical law. It was a theory that was in harmony with, and perhaps bolstered by religious doctrine. 'Nothing is so firmly believed as that which we least know' wrote French philosopher Michel de Montaigue. To Lavoisier, vitalism was the same as the phlogistion theory of combustion-a theory born from ignorance, a theory that conveniently could not be measured, a theory one must take on faith.

Lavoisier suspected that the vital spark generated by respiration was the same as the combustion of inanimate material like fuel in a fire. His experiments established a porwerful corollary: animals inhale oxygen, the active compontent of air responsible for combustion and exhale the same gas that is released from combustion-an inert gas called "fixed air" later identified as carbon dioxide. 

He created a fancy experiment where he measured the output of heat from a guinea pig and compared it to combustion of carbon. "Respiratory gas exchange is a combustion, like that of a candle burning." Life was a slow combustion, proving the vitalists wrong. 

With Lavoisier's experiment the field of energy metabolism--long muddled by the ambiguous concept of vitalism--leapt f orward as it suddenly found clarity. Criticially, his experiments illuminated the beginning and end of the metabolic map: food + oxygen = energy + carbon dioxide.