With improvements in microscopes early in the nineteenth century, yeasts were seen to be living organisms, although some famous scientists ridiculed the idea and their influence held back the development of microbiology. In the 1850s and 1860s, yeasts were established as microbes and responsible for alcoholic fermentation, and this led to the study of the rôle of bacteria in lactic and other fermentations, as well as bacterial pathogenicity. At this time, there were difficulties in distinguishing between the activities of microbes and of extracellular enzymes. Between 1884 and 1894, Emil Fischer's study of sugar utilization by yeasts generated an understanding of enzymic specificity and the nature of enzyme–substrate complexes.