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It’s been over 40 years since we first began doing basic infection research in the urology laboratory of the Harrison Department of Surgical Research at the University of Pennsylvania, following the work of Grant Mulholland, Lowell Parsons, Robert Levin, and Stan Shrom. We studied bladder antibacterial defense mechanisms, concentrating on the bladder surface lining. This evolved into our focus on possible bladder lining abnormalities in interstitial cystitis. At that time, there was only one FDA-approved therapy for this condition, intravesical application of dimethyl sulfoxide. It took 20 years for FDA approval of the next medication, the oral drug pentosan polysulfate. Neither medication has lived up to our hopes for a reliable treatment for this disease. None of the many therapies we commonly use have cleared the admittedly low bar of safety and placebo comparison necessary for FDA approval for this indication.