John Severinghaus

1930 – June 2, 2021

The following is a Review of John’s Life by Tom Hornbein, formerly a professor and Chairman of the Department of Anesthesiology at the University of Washington School of Medicine in Seattle.A second testamonial from Philip Bickler dated Aug 23, 2021 is here.

Our lives first connected at the American Physiological Society meeting off the Atlantic City boardwalk or in Chicago in the late 1950s. After a ten-minute presentation by a young scientist, John Severinghaus would rise from the audience, come to the aisle microphone and proceed to critique the strengths and weaknesses of both the talk and its underlying science. I would marvel at the quickness of his thinking and his incisive ability to help guide us youngsters. John and I shared a common interest in how breathing responds to the hypoxia of high altitude, a bond that catalyzed our beginning friendship.

Near the end of 1963, John invited me to talk and show slides of my Everest experiences earlier that year in his living room in Ross, their home in California from the time they moved their in 1958?. Among the invitees was his protégé Ted Eger. This evening began two very special friendships in my life. Ted, my age mate, died in 2017.

John entered the world feet first on May 6, 1922 in Madison, Wisconsin, the first of three children of Elmer and Grace Severinghaus. Elmer was an endocrinologist at the Wisconsin General Hospital, giving John memories of Ralph Waters, anesthesiology’s first professor, drinking from the water cooler in the hall without removing his pipe from his mouth. At age 4 according to family legend John defined his future direction by declaring that the best thing in the world was “lektristy”. It became clear early on that he had been endowed with a surfeit of curiosity that underpinned a broad-ranging scientific inquiry throughout the rest of his life. Taking things apart to find out how they worked, putting them back together to work again, sometimes even better, was an insatiable passion of his early years.

Severinghaus attended Haverford College, a small Quaker men’s school, from 1939 to 1943, refocusing from a possible future as physician like his father to physics and then doing radar research at MIT. The detonation of the atomic bomb on Hiroshima was for John a tipping point, turning him away from physics back toward a life in medicine with a biophysics emphasis on the use of electronics in biology and medicine.

John met Elinor Peck, a Wellesley art major, during those college years. He began medical school at the University of Wisconsin and then transferred to Columbia University in New York. He and Elinor married during the summer of 1948. Before he began anesthesia training, the two of them undertook mission work on the Navajo Reservation in Arizona and with Spanish American farmers in New Mexico.

Curiosity once more intruded, and with a nudge from Robert Dripps, founding chair of anesthesiology at the University of Pennsylvania, Severinghaus began residency training in 1952. He devised a simple spirometric method to measure the uptake of the anesthetic gas, nitrous oxide, presenting this research at a national meeting while a proud father sat in the audience. This study may well have been the catalyst for the investigative career of John’s most distinguished research trainee, Dr. Edmund Eger. After 6 months training, John entered the laboratory of Dripp’s colleague, Julius Comroe. When the doctor draft came along, Comroe enabled JWS’s assignment to the Public Health Service, based in the Clinical Center of the NIH when it opened in July 1953. Only partly trained in clinical anesthesia, John was appointed Director of Anesthesia Research. There he met Stuart Cullen, chair of anesthesia at the University of Iowa. Three years later he joined Dr. Cullen’s department to complete his clinical anesthesia residency and begin his academic career.

When Comroe was recruited to the University of California San Francisco medical school in 1958 to create the Cardiovascular Research Institute (CVRI). John was one of the bright, young scientists he induced to join him. This move came coupled with the recruitment of Stuart Cullen to effect the conversion of anesthesia at UCSF from a division of the Department of Surgery to a freestanding department.

What followed for John was a lifetime of adventure as a clinician, educator and most-of-all searcher for understanding. He played a major role in the maturation of the CVRI and the Department of Anesthesiology, both of which were quickly to become leaders on the national scene.

In 2008, as a measure of the esteem with which his research was held, the American Society of Anesthesiologist created a new lectureship at their annual meeting: The John W. Severinghaus Lecture on Translational Science. John was its first lecturer with a talk entitled Bench to Bedside: Gadgeteering for Healthcare. In reminiscing on his life as a gadgeteer, John touched on a number of examples, among them an electrophrenic nerve stimulator to effect non-invasive artificial ventilation, transcutaneous monitors of PO2 and PCO2, a complex circuitry of thin tubes to deliver breathing gases from patients in multiple operating rooms to a centrally-located mass spectrometer to monitor anesthetic gas concentrations (now passé as newer technology enabled individual operating room specificity), quality assessment and function of pulse oximeters, and one I lived with intimately for many years of my research life, the Severinghaus blood gas calculator, a slide rule permitting respiratory and metabolic acid-base quantification on one side and the assessment of blood oxygenation on the other. No ordinary gadgeteer.

But as John’s gadgets go, one is in a league all by itself-the blood-gas analyzer. This device that he and his technician, Freeman Bradley, produced to enable measurement of the PO2, PCO2 and pH of blood easily and rapidly was at the front point of a major transition in the practice of medicine, namely bringing physiological assessment and titration of care into the realm of assessing and managing the cardiovascular, pulmonary and renal status of high-risk, extremely ill patients. Blood gas analysis allowed surgical and other interventions that would have been the kiss of death in an earlier time. Not only was anesthesiology transformed from art to science, but the whole field of critical care medicine followed. This evolution is not a trivial event, akin in magnitude to the discovery of antibiotics and anesthetics that effected a sea-change in what medicine could do to save lives.

Blood-gas analysis is now a routine analysis performed in acute care hospitals worldwide; the original prototype with the three electrodes housed in a Plexiglas temperature-controlled water bath resides in the Smithsonian Museum. Its birth in the 1950s depended upon a series of small but critical steps:

In 1954, at a meeting of the American Physiologic Society in Madison, Wisconsin John encountered Richard Stow. Stow developed an electrode to measure the partial pressure of CO2 in blood or other fluids by placing a gas permeable membrane over the end of a pH electrode; CO2 diffused through the membrane to change the pH of the water bathing the pH glass. The problem, Stow found, was that the electrode was unstable. John suggested adding a bicarbonate buffer to the water. Problem solved and what became known as the Stow-Severinghaus PCO2 electrode was born.

Two years later at a gathering John assembled, Leland Clark reported on his work with a PO2 electrode, an oxygen polarograph with a platinum tip, covered by a gas-permeable membrane to prevent blood from “poisoning” the electrode tip. Until the tip was miniaturized to decrease its oxygen consumption, samples had to be stirred or flowed continuously past the electrode tip.

None of these discoveries of Stow, Clark, or Severinghaus represented profound breakthroughs in scientific thought, but collectively they catalyzed the transformation of the practice of medicine.

Beyond gadgeteering but truly enabled by it, John had grown curious how breathing and brain blood flow were regulated during acclimatization to the hypoxia of high altitude. Here is where my and John’s scientific interests intersected. Studies were performed on human volunteers (read each other) after rapid ascent from sea level to the Barcroft laboratory at 12,470 feet in the White Mountains near Bishop, California, gifting John a near-disabling headache after spinal puncture to measure the pH of cerebrospinal fluid. These studies in the 1960s were catalyzed in part from those of his colleague Bob Mitchell, who together with Hans Loeschke, discovered the existence of CO2 sensing receptors on the ventrolateral surface of the brainstem of cats; this CO2 responsivity led to the question of what role pH played in the increased breathing that transpired after a very few days of exposure to high altitude. Later studies folded regulation of cerebral blood flow into this same model. John became a leading authority on acid-base balance in the body, collaborating in research and writing with leading Danish scientists, Poul Astrup and Ole Sigaard-Anderson. With Astrup he produced a book entitled The History of Blood Gases, Acids and Bases.

Throughout this feast, John touched and enriched the lives of many others, both his own mentors, Comroe, Cullen and Dripps, and his contemporaries, and many younger scientists, among them colleagues Mitchell, Roughton, Neils Lassen, Cedric Bainton, George Gregory, Soren Sorenson and Phil Bickler.

As John aged and his curiosity (if possible) broadened, his interest in the historical antecedents of his scientific life ripened and he became an inspiring voice on precious moments of discovery, focusing in particular on the history of high altitude research, including his own at the Barcroft Laboratory and in Peru, and on the history of the discovery of oxygen.

John and Elinor produced four children: Ed, Wendy, Jean, and Jeff. In 20??, Elinor had a severe stroke and was moved to a nearby nursing home for care. I discovered yet one more aspect of John, I had not known before, a tenderness and patience reflecting a relationship of many years together. Imagining John in his early 90s, pedaling his bike each day from their home in Ross to visit Elinor speaks volumes, not only of their relationship but of the breadth and depth of John Severinghaus’s simple humanity and committed caring.

Among the many, varied bits I learned from John was the fun of his favorite Danish poet, Piet Hein. In the first of Hein’s three volumes of Grooks was one that, for me at least, captured a special essence of John:

I’d like to know
what this whole show
is all about
before it’s out.

Piet Hein, Grooks I