The theory of an anti-tumoral response of the immune system "in vivo" was recognized by the physician William B. Coley. In 1968, Gale A Granger from the University of California, Irvine, reported a cytotoxic factor produced by lymphocytes and named it lymphotoxin (LT). Credit for this discovery is shared by Nancy H. Ruddle from Yale University, who reported the same activity in a series of back-to-back articles published in the same month. Subsequently, in 1975 Lloyd J. Old from Memorial Sloan-Kettering Cancer Center, New York, reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). Both factors were described based on their ability to kill mouse fibrosarcoma L-929 cells. These concepts were extended to systemic disease in 1981, when Ian A. Clark, from the Australian National University, in collaboration with Elizabeth Carswell in Old's group, working with pre-sequencing era data, reasoned that excessive production of TNF causes malaria disease and endotoxin poisoning.