Automobile engine "knock" is a hammering or pinging sound associated with unusual engine vibration and consequently increased engine wear. It is caused by uncontrolled ignition of the compressed gasoline/air mixture in the engine's pistons. The irregular stresses built up harm the piston and cylinder materials and result in the knocking sound and engine wear.
Following their systematic research protocol of first defining the problem, Kettering and Thomas Midgley, Jr. used a monograph to inspect the action of pistons in their test engine and found that the knock was not caused by premature ignition from the self-starter battery arrangement but by pressure increase after spark plug ignition. Their next step was to pose a series of possible theories and go about testing each one. They decided that the solution lay in using a gasoline additive so a variety were proposed and tried and their results evaluated.
The first experiment tested the theory that red-colored material might absorb heat and correct the cylinder conditions. Iodine, being red, was tried successfully but a follow-up with red aniline dyes failed, disproving the "red coloring" theory. Next, colorless ethyl iodide proved effective and their chemical research continued. The team was diverted to work on aircraft fuels during World War I and tested a wide range of chemicals for aviation applications: ethanol, petroleum aromatics such as benzene, petroleum olefins, ethers, and paraffins. Their final decision recommended a mixture of benzene and gasoline but the war's end cancelled production plans and the researchers returned to civilian pursuits. Again iodine was the best anti-knock candidate but it was corrosive and expensive. Enthusiasm waned and research bogged down until Kettering happened on an article about the effectiveness of selenium as an additive; Midgley was re-energized. His new approach was to create a list of elements as candidates and systematically check the effectiveness of each in his one-cylinder laboratory test engine. The list included tellurium, arsenic, silver, silicon, germanium, lead, and tin.
In December, 1921, after seven years of research, it was found that very small amounts of lead, dissolved in ethanol and added to gasoline, removed the engine knock completely. Engine power and efficiency increased and tetraethyl lead became the leading gasoline additive for many years to follow, until realization of the dangers of atmospheric lead came about.