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Stanley J. Dudrick, M.D., 1935-2020

Stanley Dudrick, one of the Associationís most distinguished members died on January 18, 2020. Research he conducted while a surgical resident at the Hospital of the University of Pennsylvania (HUP) (1962-67) established total parenteral nutrition. TPN has saved millions of lives and is considered one of the 20th centuryís most important contributions in all of Medicine. The importance of this research and Stanís further contributions to nutritional science were the basis of some 150 major awards and prizes including the most prestigious ones of the American Medical Association, the American Surgical Association, the American Academy of Pediatrics and many other scientific societies. Pennís surgery department and medical school have named him their most distinguished graduate. Endowed chairs, hospitals and streets have all been named for him. On the internet one can find the names of the other awards, number of publications, honorary degrees, foreign fellowships and society leadership roles.

But as I mused about the loss of my friend I was not thinking about the prizes. Instead I was reflecting on his personal qualities, remembering him and his colleagues when they were Penn surgical residents and reviewing how Stan got so famous. It was the 1960s, a time when open-heart surgery was just beginning and transplantation, laparoscopic and endovascular surgery and gene therapy were still a way off in the future. At the time we didnít realize that what Stan was doing on a rotation in the surgical labs with a few dogs would, 6 decades later, be compared favorably with these other important medical advances.

Stanís fellow residents were in fact also quite good. During the years while Stan was training at HUP a dozen of Jonathan Rhoadsí other residents were destined to become University department chairs. I guess Stan was the best of the bunch. In fact, Medscape ranks him as one of the top 25 most influential physicians of the last century. But how did our friend get to be so exceptional? I had a front row seat and I didnít know. When asked, Stan often credited his success to his mentors and his professional lineage.

He dwelt on the importance of professional heritage and claimed that it was unique to surgeons and lacking in other specialists. As his own professional linage Stan cited John Hunter (the father of scientific surgery), and Penn surgeons William Shippen (Pennís first surgery professor who was trained by Hunter), D. Hayes Agnew, I.S. Ravdin and Jonathan Rhoads. With a pedigree like that, he said that great things were to be expected. So let's look at Stanís professional heritage, his family background and his career to see if we can understand how he became so accomplished and honored.

Stan grew up in Nanticoke, a little town in Pennsylvaniaís coal mining country. His Polish immigrant grandfather worked in the mines as did his father as a teenager before he graduated from college and bought a farm where Stan worked as a boy. Stan was a talented and ambitious kid who couldn't wait to spread his wings and get away from his home town which he remembered as being grimy, smoky and smelling of the mines. He loved college at Franklin and Marshall which he found clean and attractive. There he was highly successful, Phi Beta Kappa, class president and voted the outstanding member of his graduating class. Then during medical school at Penn where he was also class president, he first explored surgical research during a summer job by working for heart surgeon Charles Kirby. He learned the intricacies of equipment and instruments used for the newly evolving procedure of cardiopulmonary bypass, learned them so well that he was hired as a technician to run the heart lung machine for open heart operations in both experimental animals and human patients. He also recalled that during animal experiments he was taught to operate by surgical resident Horace MacVaugh.

Then as a surgical resident at HUP, Stan became interested in surgical metabolism and nutrition. This led to a close relationship with surgery chairman Jonathan Rhoads, who had a similar focus on nutrition that he had inherited from his chief, I.S. Ravdin. For years both of these legendary senior surgeons had dreamed of rescuing malnourished patients who were dying because they couldnít eat. Their longstanding research goal was supplying these patients with sufficient calories by vein to sustain them until they could eat. Not surprisingly this had also become the research assignment of a long list of HUP surgical residents who signed up to work in the lab of their chief, Jonathan Rhoads. Their attempts included giving high calorie lipid preparations by vein or administrating potent diuretics to help the patients get rid of excess water in high volume infusions. In another approach, increasing the concentration of intravenous nutrients to provide more calories sclerosed the peripheral veins used for the infusions. These experiments resulted in numerous publications but never reached clinical usefulness.

At first Stan was just one more surgical resident working on intravenous nutrition in Rhoadsí lab and frustrated by the same problems as his predecessors. But Stan proved to be more imaginative, more persistent and harder working. To follow every step of the way in Stanís own account of his research trail, read the 66-page oral history he gave to the American Academy of Pediatrics. One step was infusing hypertonic solutions to a vein in his own arm. To his remorse he confirmed that this led to painful sclerosis. This experience was a stimulus for Stanís conviction that concentrated nutritional solutions could only be delivered successfully via high volume, fast flow central veins where they would provoke neither clotting or sclerosis. He first threaded catheters from the jugular vein into the superior vena cava or right atrium. This was tolerated and he was convinced that it would allow sufficient caloric delivery. But the dogs soon displaced the catheters, preventing the long-term treatment that would be necessary.

Some accounts of the story indicate that it was Rhoads at this point who suggested they document the growth of newborn puppies to prove that they could live on IV feedings alone. In order to accomplish chronic treatment an ingenious harness was designed that the dogs could wear moving freely in their cages and not disturbing the flow of nutrients being administered 24/7. The harness secured and protected the intravenous cable with a swivel device that prevented tangling. This was the important contribution of Harry Vars, an imaginative inventor of laboratory equipment such as this indispensable device. In addition, Vars the surgery departmentís PhD biochemist helped Stan concoct the optimal mixture of essential amino acids, minerals and vitamins necessary to keep the dogs healthy and growing. This unsung hero of the story deserves to be remembered.

Stanís continuous and almost sleepless attendance and care of the puppies over several months was the feature most essential to the success of the experiment that demonstrated normal growth of the pups nourished only by vein. It was a classic. Despite there being only 4 pups in the study it was absolutely convincing. No statistics were needed.

In April of 1968 while the puppy work was still in the early publication stage a starving human infant showed up at CHOP. Intestinal atresia and 2 failed operations had left the baby with less than an inch of functional intestine. Death was inevitable and immanent. Stan was called. Working closely with HUP resident Doug Wilmore he succeeded in cannulating the central venous circulation with tiny catheters. Intravenous nutrition kept the baby alive and growing normally for more than a year.

The accomplishments of 1967-68 alone would have been enough to place Stan Dudrick in the pantheon of surgical research. But there was more to come. Stan accessed the central venous circulation with a cannula introduced by percutaneous puncture of the infraclavicular subclavian vein. This was the key to long-term treatment in human patients. Other important contributions were the introduction of home TPN, treatment of renal failure patients and promoting closure of intestinal fistulas.

After finishing his residency and only 5 years on the Penn faculty Stan was recruited to the University of Texas, Houston as the inaugural chairman of surgery in this new school. Modeling his department after HUP, over the next decade he trained a number of surgical residents who became department chairs or deans such as John Daly, Ted Copeland, Tom Miller and Wiley Souba. In 1988 Stan came back to Penn as chief of surgery at Pennsylvania Hospital. In 1994 he accepted an appointment as professor of surgery at Yale and for most of the rest of his career he served as chairman of surgery at St. Maryís, a Yale affiliated teaching hospital. In his final few years, too restless and too committed to service to retire, he taught at Geisinger Commonwealth Medical School. Ironically this new school was near his old home town.

Total parental nutrition ranks close to the top of medical research accomplishments of the 20th century. Because of its fame and importance, I suppose it was inevitable that there would be discussions about who was primarily responsible for TPN, Rhoads or Dudrick, the lab or the worker? In fact, over the yearís ardent proponents of one or the other investigator have disagreed. An illustration of this can be seen by reviewing the sequence and timing of prizes that were awarded to them by the American Surgical Association (ASA), prizes honoring the same TPN work. In 1979 the ASA gave its highest award, the Medallion for Scientific Achievement to Jonathan Rhoads as an individual. Thirty years later in 2009 the American Surgical Association gave the same Medallion for Scientific Achievement to Stan Dudrick as an individual. These and many other awards went to one or the other of them or sometimes both, such as the ASAís Flance-Karl Award in 1997. But over time the pattern of distribution changed. During the first decade and a half TPN virtually always was attributed to the senior and much better known Rhoads while Dudrick was likely to be mentioned only as an afterthought as part of the Rhoads team This wasnít fair!

As Rhoads retired and faded from the scene while Dudrick continued to work productively in the field he was likely to be credited as sharing the award. In the last few decades it has been recognized that it was Dudrick that actually contrived and conducted the crucial experiments. Thus it is with justification that Stan now dominates accounts of the TPN research. Rhoads is often not mentioned at all. This isnít fair!

The truth is that Rhoads and Dudrick were both indispensable in the creation of TPN. Without Rhoads Dudrick as a young resident on his own would never have had the opportunity or support to carry out the experiments and perhaps not even an interest in the nutrition field. Without Dudrick the definitive experiments might never have been envisioned and accomplished. Fortunately, from the very beginning the two surgeons recognized and were happy with their interdependence. While accepting the many prizes that came to each of them they were unfailingly generous and gracious in crediting the other as a necessary partner.

So what was it that made Stan so special? His small town background, his native qualities of honesty, generosity, energy and drive were all important, perhaps necessary. But I believe another part of the formula was the importance he placed on his professional forbearers and heritage. Ravdin and Rhoads were responsible for the Departmentís original focus on surgical physiology, biochemistry and nutrition, all essential for the TPN work. I would like to think it was the Penn surgery departmentís culture that prompted Dudrick and Rhoads to be so gracious in sharing the credit for TPN. Both of them were intensely proud of and loyal to their Penn lineage and to the history and traditions of our department. They felt honored to be part of this long and illustrious linage and were committed to passing it on to future generations.