Collen, KU Leuven and Genentech agreed to collaborate on the production of a recombinant version of t-PA (rt-PA), embarking on a new model for drug development: academic and biotech collaboration, today routine, but at that time a new modus operandi. Within 18 months, Pennica and her team had cloned the cDNA (complementary DNA) of human t-PA messenger RNA and was producing rt-PA in cultures of Chinese hamster ovary cells. The therapeutic potential of rt-PA and its functional identity with natural t-PA was proven in a collaboration with Steven R. Bergman and Burton Sobel (Washington University School of Medicine, Saint Louis), Frans Van de Werf (KU Leuven), and Herman 'Chip' Gold and Tsunehori Yasuda (Massachusetts General Hospital, Harvard Medical School, Boston) using canine models of coronary thrombosis. Also in 1981, following a discussion with Alfons Billiau at a scientific congress in Amsterdam, Dutch nephrologist Willem Weimar of the Dijkzigt Hospital in Rotterdam treated for the first time a patient with t-PA purified from the Bowes Melanoma Cell line. The patient, a 29-year-old lady, was suffering from a renal transplant vein thrombosis and was successfully treated resulting in a decennia-long survival. Cardiologists Frans Van de Werf and Burton Sobel tested t-PA in 1983 in a pilot clinical study on patients with acute myocardial infarction. Also in 1983, the first prospective, randomized and placebo-controlled trial of recombinant t-PA took place in three US hospitals. The subsequent NIH Thrombolysis in Acute Myocardial Infarction (TIMI) trials led by Eugene Braunwald (Brigham and Women’s Hospital, Harvard School of Medicine, Boston), and the European Cooperative Study Group Trials led by Marc Verstraete (KU Leuven) culminated in the final approval of rt-PA as thrombolytic agent by the FDA on 13 November 1987. Genentech immediately started to market the drug in the US under the brand name Activase®, while Boehringer Ingelheim would distribute the drug in the rest of the world (except Japan) as Actilyse®. The controversy over whether the more expensive rt-PA was clinically superior over streptokinase as a thrombolytic agent climaxed in the scientific press between 1988 and 1992.