Paul M. Quinton
The most prevalent force in shaping my career has been the genetic disease, Cystic Fibrosis (CF). As a sophomore at the University of Texas, Austin, in the process reading about bronchiectasis I found that my respiratory problems and other symptoms coincided well with the description of CF. That discovery began a route into a pre-med program that permitted studies in the basic sciences with a degree in English in 1971 that resulted, not in an MD, but a PhD in cell biology from Rice University in 1975 under Dr. Charles Philpott. In the meantime, I participated in an exchange program in Chile and worked part-time in the Houston CF Clinic under Dr. Gunyon Harrison.
Cystic Fibrosis was not described as such until 1938, and still in the ‘70’s, little was established about the rarely recognized disease, but it was known that: 1.) it was inherited as a Mendelian recessive, 2.) patients almost always died before adolescence of obstructed airways, 3.) patients became pancreatic insufficient with malabsorption, and 4.) without exception, patients excreted sweat with salt concentrations 3-4 times normal. Of the affected organs, it seemed to me clear that only sweat glands escaped pathological remodeling and were sufficiently accessible to be investigated in their native state for a basic defect. Consequently, as a post-doc in physiology under Dr. John Tormey at UCLA, I began attempts to isolate and micro-perfuse segments of sweat glands isolated from biopsies of human skin. Initially, it seemed impossible, but with strategic instruction and advice from Dr. Jared Grantham, who had developed microperfusion of isolated renal tubules, I learned to isolate and microperfuse the reabsorptive duct of the sweat gland. To demonstrate viability and function in vitro, I intended to collect and analyze micro perfusates of the ducts, which led to an adventure in developing energy dispersive x-ray analysis for pico-liter volumes of fluids. Fortunately, Dr. Tormey and Dr. Claude Lechenne, pioneers in x-ray analysis of tissues and fluids, were as generous as indispensable with their advice and instruction. Over the next few years as a Post-doc, Research Associate, and then Assistant Professor at UCLA, I applied this technique to measure elemental (Na, K, Cl, S, P, Ca, Mg) concentrations in micro perfusates as well as sweat from single sweat gland, and also presented the first measurements of the composition of fluid secretions from single submucosal glands of the airways. Distressingly, chemical analysis was not sufficiently informative, and Dr. Maurice Burg crucially advised applying electrophysiology. More distressing, I was not an electrophysiologist.
These pursuits were driven by the quest, which continued throughout my career. to understand the connection between a defect in electrolyte transport in CF and the abnormally thick mucus elaborated in target organs (for which the disease was also named, “Mucovisidosis”). Overall, there are perhaps three fundamental contributions that developed sequentially from our work to help interpret both the pathophysiology of Cystic Fibrosis and the normal physiology that it disrupts; that is, 1.) the role of Cl- conductance in salt transport, 2.) the essential role for HCO3- in forming mucus, and 3.) the integration of function with structure in fluid maintenance in small airways.