His account of this case also shows that he appreciated the concept that paralysis on one side of the body indicated compression on the opposite side of the brain. This patient, who crucially did not have a fracture, demonstrates Hills appreciation that it was injury to the brain that caused symptoms rather than the fracture itself. Percival Pott (1714–1788) by contrast would only operate if a fracture were present. Hills understanding of concepts of cerebral compression is demonstrated further by his use of the word ‘compression’ and by his recording of cerebral pulsation or tension in all but one of the operations described. Both of his patients who exhibited poor or absent cerebral pulsation had sustained primary cerebral damage and both died. Hill more than any other eighteenth century writer appreciated the importance of cerebral pulsation as an indicator of cerebral health. Further evidence of his understanding of the need to decompress where possible is shown by his use of the technique of relieving pressure by shaving off cerebral hernias caused by raised intracranial pressure, a technique he learned from the writing of Henri Francois Le Dran (1685–1770). Hills outcomes in treating patients with head injury compares favourably with those of his contemporaries with a mortality rate of 25%, much lower than that of le Dran (57%) or Percival Pott (51%). This was the result of Hills appreciation of the concept of cerebral compression and his better understanding of the indication for and location of the trephine.
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. Approvals and indications
Trabectedin was first trialed in humans in 1996. Soft tissue sarcoma
In 2007, the European Commission gave authorization for the marketing of trabectedin, under the trade name Yondelis, "for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents". The European Medicine Agencys evaluating committee, the Committee for Medicinal Products for Human Use (CHMP), observed that trabectedin had not been evaluated in an adequately designed and analyzed randomized controlled trial against current best care, and that the clinical efficacy data were mainly based on patients with liposarcoma and leiomyosarcoma.