The method was originally investigated by Otto Rosenheim while examining and improving on the methods by  German British chemist Otto Hehner
(1853–1924) that was used to detect formaldehyde in milk by adding sulphuric acid, which produced a blue ring. Acree noticed the reaction's similarities with the Adamkiewicz reaction and the reaction noticeably higher in casein. Based on this 1906 research, Acree investigated the reaction in 1907 in the general context of formaldehyde reactions with all forms of protein and was the first to find the importance of the  tryptophan group in the reaction, which can be extracted from casein in milk.