Zirkle demonstrated that the idea of inheritance of acquired characteristics had become fully accepted by the 16th century and remained immensely popular through to the time of Lamarck's work, at which point it began to draw more criticism due to lack of hard evidence. He also stated that pangenesis was the only scientific explanation ever offered for this concept, developing from Hippocrates' belief that "the semen was derived from the whole body." In the 13th century, pangenesis was commonly accepted on the principle that semen was a refined version of food unused by the body, which eventually translated to 15th and 16th century widespread use of pangenetic principles in medical literature, especially in gynecology. Later pre-Darwinian important applications of the idea included hypotheses about the origin of the differentiation of races.