After you, please: the second Annual John W. Severinghaus Lecture on Translational Science.

BEVERLY Philip called and made my day with her invitation to give the second John W. Severinghaus Lecture on Translational Science, noting by way of encouragement that the American Society of Anesthesiologists would pay my way and add an honorarium. “Bev,” said I, “not necessary. I’d pay for that honor.” So, here I am, giving the lecture named for my greatest hero, the man who prompted my career, guided me in my scientific and personal life, and led me to vistas I otherwise would not have seen. And doubling the pleasure, I am introduced by my best friend and colleague of a half century, Larry Saidman, who, although not named, shares the honor of this lecture. As I will write, much of the work I have done resulted because Larry and John pointed the way. “After You, Please” is an apt description of my life with these two dear friends and other colleagues with whom I have worked and whom I have admired. I claim little that is original. As you will see, this is not false humility. My career in anesthesia began on a pleasant spring day in 1952 as a newly minted first-year medical student who wished to make money as an anesthesia extern. After a 2-month summer apprenticeship in anesthesia, I would take call for my mentor, who could rest secure at home knowing that the care of emergency patients was in my capable hands. On that first day, he showed me how to start an intravenous infusion of 0.2% thiopental, dial a 70% concentration of nitrous oxide, properly hold a rubber mask to the patient’s face, and watch the rebreathing bag. Then, he left the room, and I was in trouble. The rebreathing bag moved less and less and finally stopped. I knew little of anesthesia, just information supplied in a few lectures in pharmacology, but I knew that breathing was good and not breathing was bad. My squeaky voice told the surgeon that the patient had stopped breathing. With great presence of mind, and instead of berating me for obvious incompetence, he asked if I wanted him to give artificial respiration. “Yes, please.” I responded, voice still squeaky. The surgeon squeezed the chest, the rebreathing bag now moved, and the circulating nurse fetched my mentor, who noted that the rebreathing bag could be used to ventilate the patient’s lungs. I finished the day exhausted and smelling of terror. The epiphany came as I sat thinking of the day’s events. To that moment, I had dreamed of becoming a second Robert Koch, a country physician who would make great medical discoveries as a general practitioner. A wonderfully naïve dream that suddenly vanished as I thought “You nearly killed a patient, today, and if you chose anesthesia as a career, you could do that every day. Every day you could take a patient’s life in your hands. Every day.” To a control freak (me) that image was overwhelmingly seductive. That day changed my life, a change I have never regretted. I read all the books and journals on anesthesia available to me. I sought out local anesthetic meetings. A revelation! Little was known about anesthesia, particularly about how anesthetics worked and what they did. How appealing! All of the known world of anesthesia could be explored, learned, and assimilated. God knows whether I would go into anesthesia today; the amount of present information is overwhelming. Fast forward 5 yr to my residency at the University of Iowa and an evening lecture by fellow resident (1 yr ahead of me; he is always 1 yr ahead of me) John W. Severinghaus on inhaled anesthetic uptake and distribution. Afterward, I argued with John, taking the position that if ether were more soluble, then it should act faster than nitrous oxide because more would be taken up. Like all my disagreements with John, he was right, and I was, well, hooked on uptake and distribution. For years thereafter, I spent many waking hours thinking about uptake and distribution and what factors governed the movement of inhaled anesthetics into, through, and out of the body. Two years in the Army followed residency, two wonderful years where the world mostly left me alone to muse and develop my thoughts on uptake. I invented an iterative program that predicted uptake from a knowledge of anatomy, physiology, and the gas laws. I borrowed the dietitian’s calculator, a hulking device that calculated to 21 significant places, to estimate the time course of * Professor Emeritus, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California.