In the 1780s for the French Academy of Sciences, Lavoisier, Laplace, and Seguin investigated and published relationships between direct calorimetry and respiratory gas exchanges from mammalian subjects. 100 years later in the 19th century for the Connecticut-based Wesleyan University, Professors Atwater and Rosa provided ample evidence of nitrogen, carbon dioxide, and oxygen transport during the metabolism of amino acids, glucose, and fatty acids in human subjects, further establishing the value of indirect calorimetry in determining bioenergetics of free-living humans. The work of Atwater and Rosa also made it possible to calculate the caloric values of foods, which eventually became the criteria adopted by the USDA to create the food calorie library.
In the early 20th century at Oxford University, physiology researcher Claude Gordon Douglas developed an inexpensive and mobile method of collecting exhaled breath (partly in preparation for experiments to be conducted on Pike's Peak, Colorado). In this method, the subject exhales into a nearly impermeable and large volume collection bag over a recorded period of time. The entire volume is measured, the oxygen and carbon dioxide content are analyzed, and the differences from inspired "ambient" air are calculated to determine the rates of oxygen uptake and carbon dioxide output.
To estimate energy expenditure from the exhaled gases, several algorithms were developed. One of the most widely used was developed in 1949 at University of Glasgow by research physiologist J. B. de V. Weir. His abbreviated equation for estimating metabolic rate was written with rates of gas exchange being volume/time, excluded urinary nitrogen, and allowed for the inclusion of a time conversion factor of 1.44 to extrapolate to 24-hour energy expenditure from 'kcal per minute" to "kcal per day." Weir used the Douglas Bag method in his experiments, and in support of neglecting the effect of protein metabolism under normal physiological conditions and eating patterns of ~12.5% protein calories, he wrote:
:"...In fact if the percentage of protein calories [consumed] lies between 10 and 14 the maximum error in using [the equation] is less than 1 in 500."