During the 1950s and 1960s, the National Cancer Institute carried out a wide-ranging program of screening plant and marine organism material. As part of that program, extract from the sea squirt Ecteinascidia turbinata was found to have anticancer activity in 1969.
Separation and characterization of the active molecules had to wait many years for the development of sufficiently sensitive techniques, and the structure of one of them, Ecteinascidin 743, was determined by KL Rinehart at the University of Illinois in 1984. Rinehart had collected his sea squirts by scuba diving in the reefs of the West Indies. The biosynthetic pathway responsible for producing the drug has been determined to come from Candidatus Endoecteinascidia frumentensis, a microbial symbiont of the tunicate.
The Spanish company PharmaMar licensed the compound from the University of Illinois before 1994 and attempted to farm the sea squirt with limited success. Yields from the sea squirt are extremely low -  1 tonne of animals is needed to isolate 1 gram of trabectedin - and about 5 grams were believed to be needed for a clinical trial so Rinehart asked the Harvard chemist E. J. Corey to search for a synthetic method of preparation. His group developed such a method and published it in 1996.  This was later followed by a simpler and more tractable method which was patented by Harvard and subsequently licensed to PharmaMar.  The current supply is based on a semisynthetic process developed by PharmaMar starting from safracin B, an antibiotic obtained by fermentation of the bacterium Pseudomonas fluorescens. PharmaMar entered into an agreement with Johnson &  Johnson to market the compound outside Europe.