Isaac L. Drege, whose initials are often given as J.L. instead of I.L., was the son of Carl Friedrich Drege* and his wife Sophie Christine Auguste Drege. He trained as an apothecary and settled in Port Elizabeth, where he specialised in importing German drugs and patent medicines, and served the German settlers in the surrounding areas. His activities as a naturalist started in March 1886, when he joined the Eastern Province Naturalists' Society (founded in 1882). At the society's annual meeting in January 1887 he was elected a member of its committee of management, and re-elected for two more years. This society was closely associated with the Port Elizabeth Museum, and Drege served on the first museum committee in 1887-1888. In later years he was the committee's secretary and treasurer during 1903 and the first half of 1904. His active support of the museum was acknowledged by the curator, A. Marshall*, in his report for 1895: "To Mr. J.L. Drege of this town special thanks also are due, seeing that for years past his zeal in behalf of the prosperity of the Museum has never slackened, his gifts have been many and valuable, and he has not spared himself, either in the time required to procure, or the money to purchase, any object that... would tend to enhance the general well-being of the institution". Drege's donations included 360 beetles and some birds (1894), several birds, 41 reptiles, and some insects (1895), a collection of 340 moths and other natural history specimens (1896), various birds (1898) and a variety of zoological specimens (1899). He also provided almost daily advice and assistance to the curator.
Drege also cooperated with the South African Museum in Cape Town. He donated some scorpions, nematodes (roundworms), and a collection of fresh-water crustaceans which he had collected near Port Elizabeth in 1897. The next year he contributed some arachnids, and at the museum's request bought certain specimens for its collections. His zoological knowledge is shown by the fact that the nine species of Hymenoptera and ten of Coleoptera that he donated in 1899 were all new to the museum's collections. That year he also contributed 49 species of spiders new to the museum, some vertebrates, and some scorpions. Years later he continued his donations with freshwater leeches from Port Elizabeth (1906), some insects, including a new species of the coleopterous genus Cupes (presumably Cupes capensis) not then known to occurr in South Africa (1907); a collection of plants, including some species new to the museum (1908), and some more Coleoptera (1909).
In 1905 Drege first presented plants to the Albany Museum in Grahamstown and continued his donations to at least 1913. By 1908 he was systematically botanising the district of Port Elizabeth, though he also collected in the districts of Uitenhage and Albany. His donations in 1909 included a liliaceous plant belonging to a new genus, which was named Neodregea glassii in his honour. A few years later he published a "Preliminary list of flowering plants, ferns, and fern allies, found in the Port Elizabeth district" in the Report of the South African Association for the Advancement of Science for 1912 (pp. 151-175). As co-author with Rudolf Marloth* he also contributed to "Notes on some South African mistletoes and their hosts" in the Report for 1914 (pp. 402-403). He was furthermore a painter of botanical watercolours. Years later he was thanked by W.T. Thiselton-Dyer in the Preface to Volume 5.2 (1924) of the Flora Capensis for his contribution of living and dried specimens of Euphorbia.
Drege joined the South African Philosophical Society in 1898 and remained a member when it became the Royal Society of South Africa in 1908. By 1910 he was also a member of the South African Association for the Advancement of Science. In 1906 he was a town councillor of Port Elizabeth. He was married to Christiane Alwine Drege, with whom he had at least three children.