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Thomas Grover Orr and clinical investigation
Thomas
Grover
Orr and Clinical
Investigation* STANLEY R. FRIESEN, M.D., Kansas
From the Department of Surgery, University of Kansas School of Medicine, Kansas City, Kansas 66103.
City, Kansas
were his close friends and professional colleagues, but because I knew him from the time when I followed him with the awe-stricken view of a young medical student, to the time when I returned to the more comfortable position of sharing adjacent ofices with him at the University of Kansas. I will cherish those latter days, when he was “always there” with his practical as well as philosophic advice. Surgery, apparently, was his hobby; his concern for the direction in which surgery was to go was often a topic about which he expressed ideas. We had such a chat just before he left our offices for the last time, not knowing that he would re-enter the hospital late that night with a fatal coronary occlusion on November 19, 1955. I mentioned that some of you may have had a closer acquaintance with Dr. Orr than did I, either as resident or a advocate or adversary. Will anyone deny, for instance, that a resident in surgery, during his period of training under a demanding and seemingly unreasonable chief of the service, gets to know that chief better than does anyone else? Those of you who were his residents will know of his relentless expectation of perfection in the care of patients. I shall never forget, for instance, one night during a time when I was a surgical extern, Dr. Orr had allowed his senior resident to perform (with the Chief’s assistance) his first radical mastectomy. Making sure that nothing was lacking in postoperative patient care, that resident and I changed the poor lady’s large dressings three times that night! Those of you who knew Dr. Orr through this organization or who were his colleagues i n his
very sincerely the invitation I APmmxATE present this, the third annual Thomas
to G. Or-r Memorial Lecture, at this, the twentieth annual meeting of the Southwestern Surgical Congress. One thought that sustains me at the moment is that Dr. Orr, if he were here, would put his firm hand on my shoulder, saying “You can do it, boy,” while with his other hand he might hand me a reprint of an article he had written entitled, “Doctors Making Speeches.” The article to which I refer is his Presidential Address to the second annual meeting of this same Southwestern Surgical Congress on September 25, 1950 (eighteen years ago), here in Denver, Colorado, which many of you will recall, as I do. In this address he caricatured the diverse and diverting mannerisms of medical speakers, the multifarious approaches to a scientific presentation and to the podium; he cautioned against oratory as “the ability to make deep noises from the chest seem like important messages from the brain,” and warned of speaking too long. I shall try to follow his advice. Today, to portray one of the Founders of this group of surgeons, I will attempt to assess his contribution to surgery through an analysis of his publications. I particularly would like to develop his role as a clinical investigator of his time and comment briefly on the increasing importance of clinical investigation today. I believe that I have a certain, although humble, right to speak of him (Fig. 1) and his work, not that I may have known him any more intimately than did many of you who
* Presented at the Twentieth Annual Meeting of the Southwestern Surgical Congress, Denver, Colorado, April 22-25, 1968. 634
The American
Journal
of
Surgery
Thomas Grover Orr active life will remember him as the second President of this group, as an original member of the American Board of Surgery, and as President of the American Surgical Association, the Western Surgical Association, and local surgical groups; as Editor of The American Surgeon, as author of two textbooks on surgery, and as the recipient of more honors than it is the privilege of most of us to receive. He received an honorary Doctor of Science degree from his alma mater, the University of Missouri, in 1954. Another honor, or recognition, that came to him during his lifetime took place in the year of his retirement as Chairman of the Department of Surgery at the University of Kansas (a position which had been his for twenty-five years). On November 21, 1949, the Kansas City newspaper headlined “A Star on His Big Day.” It was an occasion when many Kansans gathered to pay him respect while a new building was being dedicated. He performed an operation, on television, being assisted by three of his erstwhile residents who had returned for the operation, his occasion ; after this dedicatory portrait was unveiled by the Chancellor of the University, Deane W. Mallott, and a tribute to Dr. Orr was given by Dr. Owen H. WangenSteen, who said it was “Dr. Orr’s Day in Kansas.” These two surgeons had had much in common through their investigations into intestinal obstruction. Dr. Ralph H. Major, a life-long friend and colleague of Dr. Orr, has said of him that he was one of the very few men who realize their youthful dreams. While they were both students at Johns Hopkins, Dr. Orr had stated that he had two ambitions, one to be a surgeon and the other to practice in Kansas City. He did not know that those two dreams would be eclipsed by the many honors coming to him. There is a time and a period in his life about which little is known but which has the color of a vivid sunrise, so familiar to so many of you in the southwest. His love of the Americana of the Great West began at a time when there seemed to be a hesitation of purpose, after his surgical training at a New York hospital. For the greater part of a year he toured the West (in company with a young man of means) from southwest to northwest, collecting stories of Indian lore and of the pioneer history of the West. I am told that in later life he often spent a great part of his vacation during the summer, literally working as a medical missionary, helping out at a Vol. 116, November 1968
FIG. 1. Thomas Grover Orr. sr hospital on an Indian reservation in Arizona. Although, to my knowledge, Dr. Orr never wrote of these interests, his accounts of pioneering physicians such as Marcus Whitman stimulated historical searches and accounts of our western heritage. It was shortly after his first colorful trip through the West that he married Irene Helen Harris, a nurse whom he had known at New York hospital. Their son. Tom, Jr., was born in 1916 and was also to become a surgeon. Dr. Orr came to Kansas in lCjl.5 to become Professor of Bacteriology at the Medical School. He had been recommended for this position by his former school chum, Dr. Ralph Major. lvith the superlative commendation that Dr. Orr had received training in bacteriology (one semester in the second year of his medical course). His name, however, failed to appear in the medical school catalog for that year but in the catalog for the year 1915-1916 a 31~. Orr (English touch!) appears as Instructor in Surgery. His ambition for surgery apparently was recognized early, and he was appropriately launched on his dream of surgery. This brief tenure, a single semester, as Professor of Bacteriology must have influenced his thinking for some time, however, since it is noted that three of his first four published articles relate to the bacteriology of infection and that at least eighteen of his publications concern infection specifically. His first impact on the field of surgery is concerned with his interest in amputations, for
Friesen
636 TABLE GENERAL ORR:
I
CLASSIFICATION OF THE PUBLICATIONS THE
INVESTIGATIONS
OF CLINICAL
BY
DR.
PROBLEMS
PREDOMINATE
Clinical investigation Animal investigation Case reports (only) Operative technic Books and chapters Philosophical Historical Administrative Total
122 46 28 16 6 6 5 2 231
which he is still remembered. His publications on this subject immediately followed his military service (191%1919), and culminated in 1926 in the well known monograph entitled “Modern Methods of Amputation.” A picture of his personality, of his inquisitiveness, and of his sense of obligation to his chosen field of surgery is to be found in the following account of a clinical situation. Dr. Orr had been called in consultation to see a patient on the medical service who had a bleeding ulcer. His medical colleague had put the patient on a new anticholinergic drug which has a side effect of producing atony of the gastrointestinal tract and bladder. Dr. Orr was impressed by the resultant abdominal distention and advised immediate operation. The internist, however, was not disposed at that time to agree to immediate intervention. It is said that Dr. Orr “stomped off”-but, almost surreptitiously, would sneak back daily to get a quick look at the patient. The bleeding ceased, and in five days the intestinal ileus disappeared and the bladder tone returned. Having learned something of anticholinergic side effects, Dr. Orr strongly advised the internist to publish this observation, and, furthermore, to place it “in a surgical journal to keep dumb surgeons like me out of the belly.” His willingness to back down from a strong position, his change of mind based on his own observations, prompted his admission to a new clinical situation which, he thought, should be publicized among his own kind. He learned by critical observations of patients, and perhaps it was this type of personal involvement in clinical problems that led him to study patients thoroughly as a clinical investigator. AN
ANALYSIS
OF HIS PUBLICATIONS
Dr. Orr encouraged young physicians to re-
cord their worthwhile medical observations without fear of criticism; to begin this before the age of forty, he said, would carry them through the next twenty years with little effort. He practiced what he preached. His bibliography contains a list of 231 published articles; the first paper was published in 1912, when he was twenty-eight years of age, and was entitled “Leukocyte and Differential Counts in Ward and Open Air Treatment.” His last contribution was a complete revision of a chapter in Lewis’s System of Surgery, entitled “Hemorrhage and Traumatic Shock,” with myself as coauthor, which was published in 1957, after Dr. Orr’s death. He published four papers before coming to Kansas; 227 papers were published in the thirty-four years at Kansas, thirty-seven of these while he was in Kansas prior to becoming Chairman of the Department (in 1924), and thirteen after the year of his retirement as Chairman (in 1949) ; 177 were published during the twenty-five years that he was Chairman. Authorship of many of these articles includes the names of many of his residents and medical school colleagues, some of whom are members of this Southwestern Surgical Congress. A perusal of the content of his published papers seems to confirm his urge to make the most of clinical observations; he investigated clinical problems. If his publications are divided into appropriate categories (Table I), his interest in the investigation of clinical problems, not just case reports, is obvious numerically. The next largest group of publications concerns investigations using experimental and laboratory animals, a point on which I will comment later. Although the pure case reports number twentyeight, they are a relative minority. It is surprising that a surgeon who was so strict regarding the technic of operating would publish only sixteen articles on technic, a majority of these related to new technics, some of which concern amputation specifically. Technic, however, is emphasized in his two books, a textbook entitled “Operations of General Surgery” and a monograph on “Modern Methods of Amputation, ” and in four additional contributions as chapters in other textbooks. A more detailed classification of his publications concerned with clinical and animal investigation is listed in Table II. His investigations into intestinal obstruction and its biologic effects are important studies, which began in The American
Journal of Surgery
Thomas 1923, when he was thirty-nine years old, one year prior to his accepting the chairmanship of the department. Investigations concerning patients with intestinal obstruction, numbering twenty-eight, were coupled with appropriate investigations on experimental animals, numbering thirty-one, totalling fifty-nine, an impressive number, as impressive as their content. Several important observations can be made in regard to this surge of interest. The importance of electrolyte and water abnormalities was put on a firm physiologic basis. The work culminated in an important recommendation for the life-saving use of a gastroduodenal tube for suction in 1934, just one year after a similar recommendation by Drs. Wangensteen and Payne. This burst of energy no doubt was aided and abetted by the scientific approach to the problem by Dr. Russell Haden, who co-authored forty-seven of the fifty-nine articles on intestinal obstruction, in a brief span of eight years. Dr. Hnden may have been more than the catalyst in these investigations and, being in the right place at the right time, may have provided the impetus to investigate a condition which claimed the lives of many patients. Dr. Haden, four years younger than Dr. Orr and also a graduate of Johns Hopkins, came to Kansas in 1921 as Associate Professor of Medicine and by 1923 he was named Professor of Experimental Medicine. This date coincides with the first flurry of papers with Dr. Orr on intestinal obstruction. In that first year, they pointed out the abnormalities of sodium and chloride in obstructions and the value of their replacement. Many parameters of metabolic abnormalities were documented in intestinal obstruction in man, dogs, and monkeys, by Dr. Haden, and the clinical significance of this information and particularly the management of such patients were forcefully made practical by Dr. Orr, even after Dr. Haden had left Kansas in 1930 to become Head of the Department of Medicine at the Cleveland Clinic. The tremendous impact of the knowledge of water and salt alterations in intestinal obstruction had far reaching influence, But amid all the detailed scientific knowledge pouring out at that time, an erudite and entertaining article was published by Dr. Orr in The Scientijic Monthly (39: 449, 1934) with the title, “The Romance of Common Salt.” In this article he points out that salt has played a very important Vol. 116. November
1968
Grover
I iii:
Orr TAHLE
SUBCLASSIFICATICIS PERTAINING
‘10
OF
THE
CLISICAL
II PUBLICA’IIOSS
APiD
BSIMAL
OF
DR.
ORR
IUVE5~TIf;AIION
Clinical Investigation Intestinal obstruction Other gastrointestinal problems Peritonitis Other infections Surgical care Hepatorenal syndrome Biliary and acute pancreatitis Hemovascular Trauma Pancreatic carcinoma Endocrine system Amputations Diaphragm Tumor, generally Breast carcinoma Lung carcinoma Total
1
3
role in the development of the human race from the standpoints of war, commerce, religion, and superstition. He detailed numerous examples of the ubiquitous role of salt in ceremonies, social customs, and barter (the word “salary” comes from solarium, an allowance to Roman soldiers for the purchase of salt). His interest in the southwest again becomes apparent in his references to the place of salt in the early Indian folklore and customs. Dr. Orr was colorful when he was philosophic. At one time (Table III) in 19X1, while speaking to a group of medical students, he portrayed the lives of great men in medical history by accenting their eccentricities or their handicaps or their little-known peculiarities, to make history come alive. He urged students to pick a hero, and added that “to study medicine without your medical hero is to pocket the nut withTABLE PUBLICATIONS
OF DR.
III
ORR WHICH
MIGHT
BE
CLASSIFIED
AS PHILOSOPHIC
Year 1931 1932 1933 1934 1935 1951
Publication A Medical Philosophy Faith in Medicine Is the Family Doctor Passing? Some Problems in the Treatment The Romance of Common Salt Doctors Making Speeches
* See text for descriptions.
of Cancer
63s
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out investigating the kernel.” In his published thoughts concerning “Faith in Medicine,” he urged young physicians to honor past medical discoveries and to apply the knowledge of their predecessors to the future. In 1933 Dr. Orr was concerned about the inroads made upon the family physician by the trend towards specialization, technology, and legislation. He reasoned, in answer to his question “Is the Family Physician Passing?,” that the intimate and personal care and assurance of the family physician will always be a necessity, as was the priest-physician relationship to the sick in centuries before that. His thoughts concerning “Some Problems in the Treatment of Cancer” were centered largely on education of the lay public and physicians toward a dispelling of the gloom and the fatalistic attitude surrounding the diagnosis of cancer in 1934, a task which was energetically assumed by the American Cancer Society a decade or more later. One of his historical articles had the captivating title of “Was Ambrose Par& a Murderer?” Characteristic of the thoroughness of Dr. Orr, he reviewed the life and times of Ambrose Par& to assess the circumstances surrounding the supposed indictment of Pare as the murderer of Francis II, King of France, in the sixteenth century. Dr. Orr accumulated sufficient data to cast doubt that the ear injection described by malicious enemies as “pouring of poison into the King’s ear” was a murderous act. On the other hand, Dr. Orr recounted an episode in which Pare urged the captain of the French artillery to fire upon a group of camp followers who were a constant source of annoyance to Par& ; the cannon shots killed fifteen or sixteen women ! To return briefly to Dr. Orr’s publications in clinical investigation (Table II), many of us can recall his descriptions of the still enigmatic hepatorenal syndrome. There were five articles on this subject investigated clinically and three articles reporting animal investigation of the syndrome. The first of these articles, with Dr. Ferdinand C. Hellwig, appeared in 1932 with the title, “Traumatic Necrosis of the Liver with Extensive Retention of Creatinine and High Grade Nephrosis.” They had found only one case in the literature to parallel theirs, and they favored a theory that some toxin was elaborated in the liver through hemorrhagic necrosis which acted directly on the kidney to produce tubular necrosis. In 1939 they reported five more cases and came to the same conclusion re-
garding an unknown toxin, but also emphasized the role of hemorrhage, shock, and infection in the syndrome. Dr. Orr added in his discussion of the paper that he was not “prepared to accept this condition wholesale because there are so many other factors to be taken into consideration.” After much study and speculation on his part regarding the so-called heptorenal syndrome, we note that by 1940 the title of an editorial simply asks the still unanswered question, “Is There a Hepato-Renal Syndrome?” It probably is significant that even now, over twenty-five years later, with all our sophisticated investigative tools for liver, renal, vascular, and chemical functions, the answer is still elusive. It is interesting to note that there were only three publications concerning cancer of the breast, yet he had one of the most thorough follow-up systems and had collected much data concerning these patients. Carcinoma of the lung occupied his interest only briefly, if his bibliography is an indication of attention. In his one article on the subject (1938) he stated that “although surgical treatment has been too recent to evaluate, nevertheless pneumonectomy in selected cases offers the only definite hope of cure.” Perhaps the area most recent in our memory of Dr. Orr is in connection with his probing into the question of radical versus palliative procedures for carcinoma of the head of the pancreas. His initial articles on this subject, in 1941, stress the findings of fatty infiltration of the liver in patients operated upon for carcinoma of the head of the pancreas. His first operations were two stage procedures without pancreatic anastomosis to the intestine, which may account for the poor utilization of fat which concerned him. By 1942 he was emphasizing the use of vitamin K and restoring pancreatic drainage to the intestine, and in a period of less than four years he had performed nine radical procedures. In 1945 he published an extensive review of the literature to attempt to answer the question whether radical pancreatoduodenectomy is justifiable, and stated that the data were not very convincing. By 1946 he apparently was convinced because he stated that greater length of life has resulted with the radical operation than with any type of palliative operation. He advocated radical operation for small lesions of the ampulla and duodenum. He urged further study for final evaluation of the radical proceThe American Journal of Surgery
Thomas dure ~7~1,in 1~62, reported that a search of the literature had revealed seventeen patients who had survivetl five years or more after radical pancreatoduodenectomy for carcinoma. By this time he had performed twenty-four of the radical operations without a five year survivor but despite this he continued to advise a one stage radical operation as the most satisfactory palliative procedure. CHANGING
PICTURE
OF CLINICAL
INVESTIGATION
Clinical investigation is as old as medicine itself, if it is implied that investigation consists of detailed observation of the natural course of the disease in patients. Hippocrates and Galen made nlany clinical observations which influenced succeeding physicians for centuries. Ambrose Par& appeared not to be afraid to challenge old ideas with new ones. Lister, when he sa\v the importance of Pasteur’s contributions, made observations of his own regarding the role of antisepsis in surgery. John Hunter, however, was the investigator par excellence in surgical history when he made the observation that nature alone has the power to heal and that the surgeon helps the patient mainly by aiding the natural recovery processes. In addition to the pursuit of clinical phenomena, John Hunter sa\v the advantage of coupling human studieh with animal experimentation. This coupling of investigative efforts reached its peak in the twentieth century. Dr. Orr’s contribution to intestinal obstruction was an example in which studies on patients and on the experimental animal proceeded together. It has been controversial whether one method of investigation is superior to the other; ultimately the investigative idea begins with a clinical problem and hopefully ends with a clinical solution. The methods of reaching that solution, however, sometimes can be accomplished only by appropriately controlled studies in laboratory animals. When it is possible to obtain su&cient data from patients, the investigative aspects of the patient’s disease are, of course, most meaningful, and when in the course of these investigations data are obtained relative to that patient’s disease but which is “over and above” that which is considered pertinent to the immediate managetnent, clinical investigation may be said to be taking place. The collection of data pertinent to a patient’s disease, from the patient himself, is meaningless unless it is accurately recorded and honest Vol.116, November 1968
Grover
Orr
(Cl!)
judgments are made. The most rewarcling practice of surgery involves the discover>- that the observations tnltde in patients lead to new knowledge which can be applied with a greater promise of success in the next patient. “Poorly worked-up” patients often do not yielr! such a satisfying reward for the surgeon and seldom result in a satisfactory experience ior the patient. Whereas much can be learned from patients who are thoroughly and ideally “worked-up.” there are opportunities at the present time when disease processes, metabolic abnormalities, and results of treatment can be investigated in a more sophisticated and controlled manner. I refer to the federally-supported clinical research centers of some institutions. For the first time, appropriate and approved prospective btutlies may be made without involving the patient himself directly with the costs of such studies. The information gained usually has far-reaching benefits not only to the patient so studied but also to many other patients who become the recipients of such advances of thought and skills. My own experience \vith patients admitted to such a clinical research center is that patients readily accept the opportunity for thorough studies, some of which are impractical in an ordinary hospital environment, when they realize the potential benefit to themselves as well as to others. Dr. Orr would be agreeably surprised at the relative ease with which patients can be studied today. As Ire look at the future, we too may be surprised at the mass of data which may accrue when computerized collection of information and recall of all accumulated data become universally applicable. Whether clinical investigation of patients takes place in the usual hospital environment or in a federally-supported unit such as a clinical research center, my own experience indicates that such studies are more accurately and more efliciently accomplished in a unit set up for investigative purposes. For the past three years, I have been using a clinical research center for preoperative studies of patients in whom I expect to perform some type of gastric operation and postoperative studies of patients who have had such operations. Detailed studies of gastric secretory physiology, rdstric motor activity, and pancreatic carbohydrate metabolism are carried out more efficiently and more accurately than in an ordinary hospital environment. This type of thorough study of patients
640
Friesen
having gastric operations may lead to the development of improved operations as well as a clarification of our understanding of the abnormal physiology. In another group of patients with marked hypersecretion of gastric acids associated with endocrine tumors, a thorough evaluation of all endocrine organ functions is more likely to be fruitful in a clinical investigative unit than in an active surgical ward. In the instance of patients having ulcerogenic tumors of the pancreas, clinical studies in eleven patients have yielded the important observation that total removal of the stomach has caused a regression of metastatic nonbeta islet cell carcinoma of the pancreas. Metastases to the lung and liver have visibly disappeared after total gastrectomy. This suggests that a gastric factor plays an important role in the pathogenesis of the Zollinger-Ellison syndrome; moreover, it is suggested that the stomach influences the growth of islet cells of the pancreas.* Studies such as these, which were initiated primarily as a clinical investigation of a select group of patients, have every possibility of leading to broader solutions of clinical importance for a much larger group of patients, such as the elucidation of the causes of the more common duodenal ulcer in man. When clinical investigation is coupled with pertinent controlled laboratory investigation, the evolution of knowledge is hastened. It is acknowledged that thorough investigation is costly in terms of time and money. With the stretching of the American economy at the present time, there is a real concern whether research can continue at its present pace under federal subsidy. One solution to this problem was suggested by Dr. Wangensteen when he honored Dr. Orr upon the latter’s retirement, when he described the growing concept of private support for research. That this is possible is illustrated by the following account. Our recent reports of the gastric influence on islet cell carcinoma prompted a private donor of funds to inquire about the status of funds previ* The clinical investigations referred to here were carried out with the financial support of NIH Grant #FR-67.
ously given to the University of Kansas for cancer research. In this instance, an initial gift of $1,000, followed by one of $1,500, and then by a farm valued at $29,000 (a total gift of $31,500) was reinvested and through a series of judicious transactions, in less than twenty years the monetary value of that gift has increased to $160,000; the value to research may be inestimable. Private donations such as this, augmented by similarly-inclined donors, could have an important influence on the future of clinical investigation. Significant as private support of research may be, such amounts are small compared to the budget of the National Institutes of Health, where the intramural budget is 200 million dollars and the extramural grants and aid total 900 million dollars. The research, both clinical and laboratory, made possible by such federal support, probably is the most significant in the world, but any clinical evaluation and study of patients by any one of us who treat patients is important also. Most of us will do well if we conscientiously keep foremost in our minds that keen observation of our patients usually leads to more successful management, that a “well worked-up” patient usually “does better,” and that we as surgeons will fare more happily knowing that we have done our best and have contributed in our own way to a rapidly expanding field of knowledge. SUMMARY
The influence upon clinical investigation of Thomas Grover Orr, whom we are commemorating in this Memorial Lecture, was a significant one. Through keen observations of patients, he applied new knowledge to clinical problems. When he coupled these studies with laboratory investigations, his impact was even more significant, as with intestinal obstruction. Accomplishment of new knowledge came about most fruitfully when he worked with other established investigators, an illustration of the “team approach” to investigation. His example of thorough study of patients leads us today to use whatever means and facilities we have to further our knowledge through clinical investigation
The American
Jouvnal of Surawy
Grover
Orr and Clinical
Investigation* STANLEY R. FRIESEN, M.D., Kansas
From the Department of Surgery, University of Kansas School of Medicine, Kansas City, Kansas 66103.
City, Kansas
were his close friends and professional colleagues, but because I knew him from the time when I followed him with the awe-stricken view of a young medical student, to the time when I returned to the more comfortable position of sharing adjacent ofices with him at the University of Kansas. I will cherish those latter days, when he was “always there” with his practical as well as philosophic advice. Surgery, apparently, was his hobby; his concern for the direction in which surgery was to go was often a topic about which he expressed ideas. We had such a chat just before he left our offices for the last time, not knowing that he would re-enter the hospital late that night with a fatal coronary occlusion on November 19, 1955. I mentioned that some of you may have had a closer acquaintance with Dr. Orr than did I, either as resident or a advocate or adversary. Will anyone deny, for instance, that a resident in surgery, during his period of training under a demanding and seemingly unreasonable chief of the service, gets to know that chief better than does anyone else? Those of you who were his residents will know of his relentless expectation of perfection in the care of patients. I shall never forget, for instance, one night during a time when I was a surgical extern, Dr. Orr had allowed his senior resident to perform (with the Chief’s assistance) his first radical mastectomy. Making sure that nothing was lacking in postoperative patient care, that resident and I changed the poor lady’s large dressings three times that night! Those of you who knew Dr. Orr through this organization or who were his colleagues i n his
very sincerely the invitation I APmmxATE present this, the third annual Thomas
to G. Or-r Memorial Lecture, at this, the twentieth annual meeting of the Southwestern Surgical Congress. One thought that sustains me at the moment is that Dr. Orr, if he were here, would put his firm hand on my shoulder, saying “You can do it, boy,” while with his other hand he might hand me a reprint of an article he had written entitled, “Doctors Making Speeches.” The article to which I refer is his Presidential Address to the second annual meeting of this same Southwestern Surgical Congress on September 25, 1950 (eighteen years ago), here in Denver, Colorado, which many of you will recall, as I do. In this address he caricatured the diverse and diverting mannerisms of medical speakers, the multifarious approaches to a scientific presentation and to the podium; he cautioned against oratory as “the ability to make deep noises from the chest seem like important messages from the brain,” and warned of speaking too long. I shall try to follow his advice. Today, to portray one of the Founders of this group of surgeons, I will attempt to assess his contribution to surgery through an analysis of his publications. I particularly would like to develop his role as a clinical investigator of his time and comment briefly on the increasing importance of clinical investigation today. I believe that I have a certain, although humble, right to speak of him (Fig. 1) and his work, not that I may have known him any more intimately than did many of you who
* Presented at the Twentieth Annual Meeting of the Southwestern Surgical Congress, Denver, Colorado, April 22-25, 1968. 634
The American
Journal
of
Surgery
Thomas Grover Orr active life will remember him as the second President of this group, as an original member of the American Board of Surgery, and as President of the American Surgical Association, the Western Surgical Association, and local surgical groups; as Editor of The American Surgeon, as author of two textbooks on surgery, and as the recipient of more honors than it is the privilege of most of us to receive. He received an honorary Doctor of Science degree from his alma mater, the University of Missouri, in 1954. Another honor, or recognition, that came to him during his lifetime took place in the year of his retirement as Chairman of the Department of Surgery at the University of Kansas (a position which had been his for twenty-five years). On November 21, 1949, the Kansas City newspaper headlined “A Star on His Big Day.” It was an occasion when many Kansans gathered to pay him respect while a new building was being dedicated. He performed an operation, on television, being assisted by three of his erstwhile residents who had returned for the operation, his occasion ; after this dedicatory portrait was unveiled by the Chancellor of the University, Deane W. Mallott, and a tribute to Dr. Orr was given by Dr. Owen H. WangenSteen, who said it was “Dr. Orr’s Day in Kansas.” These two surgeons had had much in common through their investigations into intestinal obstruction. Dr. Ralph H. Major, a life-long friend and colleague of Dr. Orr, has said of him that he was one of the very few men who realize their youthful dreams. While they were both students at Johns Hopkins, Dr. Orr had stated that he had two ambitions, one to be a surgeon and the other to practice in Kansas City. He did not know that those two dreams would be eclipsed by the many honors coming to him. There is a time and a period in his life about which little is known but which has the color of a vivid sunrise, so familiar to so many of you in the southwest. His love of the Americana of the Great West began at a time when there seemed to be a hesitation of purpose, after his surgical training at a New York hospital. For the greater part of a year he toured the West (in company with a young man of means) from southwest to northwest, collecting stories of Indian lore and of the pioneer history of the West. I am told that in later life he often spent a great part of his vacation during the summer, literally working as a medical missionary, helping out at a Vol. 116, November 1968
FIG. 1. Thomas Grover Orr. sr hospital on an Indian reservation in Arizona. Although, to my knowledge, Dr. Orr never wrote of these interests, his accounts of pioneering physicians such as Marcus Whitman stimulated historical searches and accounts of our western heritage. It was shortly after his first colorful trip through the West that he married Irene Helen Harris, a nurse whom he had known at New York hospital. Their son. Tom, Jr., was born in 1916 and was also to become a surgeon. Dr. Orr came to Kansas in lCjl.5 to become Professor of Bacteriology at the Medical School. He had been recommended for this position by his former school chum, Dr. Ralph Major. lvith the superlative commendation that Dr. Orr had received training in bacteriology (one semester in the second year of his medical course). His name, however, failed to appear in the medical school catalog for that year but in the catalog for the year 1915-1916 a 31~. Orr (English touch!) appears as Instructor in Surgery. His ambition for surgery apparently was recognized early, and he was appropriately launched on his dream of surgery. This brief tenure, a single semester, as Professor of Bacteriology must have influenced his thinking for some time, however, since it is noted that three of his first four published articles relate to the bacteriology of infection and that at least eighteen of his publications concern infection specifically. His first impact on the field of surgery is concerned with his interest in amputations, for
Friesen
636 TABLE GENERAL ORR:
I
CLASSIFICATION OF THE PUBLICATIONS THE
INVESTIGATIONS
OF CLINICAL
BY
DR.
PROBLEMS
PREDOMINATE
Clinical investigation Animal investigation Case reports (only) Operative technic Books and chapters Philosophical Historical Administrative Total
122 46 28 16 6 6 5 2 231
which he is still remembered. His publications on this subject immediately followed his military service (191%1919), and culminated in 1926 in the well known monograph entitled “Modern Methods of Amputation.” A picture of his personality, of his inquisitiveness, and of his sense of obligation to his chosen field of surgery is to be found in the following account of a clinical situation. Dr. Orr had been called in consultation to see a patient on the medical service who had a bleeding ulcer. His medical colleague had put the patient on a new anticholinergic drug which has a side effect of producing atony of the gastrointestinal tract and bladder. Dr. Orr was impressed by the resultant abdominal distention and advised immediate operation. The internist, however, was not disposed at that time to agree to immediate intervention. It is said that Dr. Orr “stomped off”-but, almost surreptitiously, would sneak back daily to get a quick look at the patient. The bleeding ceased, and in five days the intestinal ileus disappeared and the bladder tone returned. Having learned something of anticholinergic side effects, Dr. Orr strongly advised the internist to publish this observation, and, furthermore, to place it “in a surgical journal to keep dumb surgeons like me out of the belly.” His willingness to back down from a strong position, his change of mind based on his own observations, prompted his admission to a new clinical situation which, he thought, should be publicized among his own kind. He learned by critical observations of patients, and perhaps it was this type of personal involvement in clinical problems that led him to study patients thoroughly as a clinical investigator. AN
ANALYSIS
OF HIS PUBLICATIONS
Dr. Orr encouraged young physicians to re-
cord their worthwhile medical observations without fear of criticism; to begin this before the age of forty, he said, would carry them through the next twenty years with little effort. He practiced what he preached. His bibliography contains a list of 231 published articles; the first paper was published in 1912, when he was twenty-eight years of age, and was entitled “Leukocyte and Differential Counts in Ward and Open Air Treatment.” His last contribution was a complete revision of a chapter in Lewis’s System of Surgery, entitled “Hemorrhage and Traumatic Shock,” with myself as coauthor, which was published in 1957, after Dr. Orr’s death. He published four papers before coming to Kansas; 227 papers were published in the thirty-four years at Kansas, thirty-seven of these while he was in Kansas prior to becoming Chairman of the Department (in 1924), and thirteen after the year of his retirement as Chairman (in 1949) ; 177 were published during the twenty-five years that he was Chairman. Authorship of many of these articles includes the names of many of his residents and medical school colleagues, some of whom are members of this Southwestern Surgical Congress. A perusal of the content of his published papers seems to confirm his urge to make the most of clinical observations; he investigated clinical problems. If his publications are divided into appropriate categories (Table I), his interest in the investigation of clinical problems, not just case reports, is obvious numerically. The next largest group of publications concerns investigations using experimental and laboratory animals, a point on which I will comment later. Although the pure case reports number twentyeight, they are a relative minority. It is surprising that a surgeon who was so strict regarding the technic of operating would publish only sixteen articles on technic, a majority of these related to new technics, some of which concern amputation specifically. Technic, however, is emphasized in his two books, a textbook entitled “Operations of General Surgery” and a monograph on “Modern Methods of Amputation, ” and in four additional contributions as chapters in other textbooks. A more detailed classification of his publications concerned with clinical and animal investigation is listed in Table II. His investigations into intestinal obstruction and its biologic effects are important studies, which began in The American
Journal of Surgery
Thomas 1923, when he was thirty-nine years old, one year prior to his accepting the chairmanship of the department. Investigations concerning patients with intestinal obstruction, numbering twenty-eight, were coupled with appropriate investigations on experimental animals, numbering thirty-one, totalling fifty-nine, an impressive number, as impressive as their content. Several important observations can be made in regard to this surge of interest. The importance of electrolyte and water abnormalities was put on a firm physiologic basis. The work culminated in an important recommendation for the life-saving use of a gastroduodenal tube for suction in 1934, just one year after a similar recommendation by Drs. Wangensteen and Payne. This burst of energy no doubt was aided and abetted by the scientific approach to the problem by Dr. Russell Haden, who co-authored forty-seven of the fifty-nine articles on intestinal obstruction, in a brief span of eight years. Dr. Hnden may have been more than the catalyst in these investigations and, being in the right place at the right time, may have provided the impetus to investigate a condition which claimed the lives of many patients. Dr. Haden, four years younger than Dr. Orr and also a graduate of Johns Hopkins, came to Kansas in 1921 as Associate Professor of Medicine and by 1923 he was named Professor of Experimental Medicine. This date coincides with the first flurry of papers with Dr. Orr on intestinal obstruction. In that first year, they pointed out the abnormalities of sodium and chloride in obstructions and the value of their replacement. Many parameters of metabolic abnormalities were documented in intestinal obstruction in man, dogs, and monkeys, by Dr. Haden, and the clinical significance of this information and particularly the management of such patients were forcefully made practical by Dr. Orr, even after Dr. Haden had left Kansas in 1930 to become Head of the Department of Medicine at the Cleveland Clinic. The tremendous impact of the knowledge of water and salt alterations in intestinal obstruction had far reaching influence, But amid all the detailed scientific knowledge pouring out at that time, an erudite and entertaining article was published by Dr. Orr in The Scientijic Monthly (39: 449, 1934) with the title, “The Romance of Common Salt.” In this article he points out that salt has played a very important Vol. 116. November
1968
Grover
I iii:
Orr TAHLE
SUBCLASSIFICATICIS PERTAINING
‘10
OF
THE
CLISICAL
II PUBLICA’IIOSS
APiD
BSIMAL
OF
DR.
ORR
IUVE5~TIf;AIION
Clinical Investigation Intestinal obstruction Other gastrointestinal problems Peritonitis Other infections Surgical care Hepatorenal syndrome Biliary and acute pancreatitis Hemovascular Trauma Pancreatic carcinoma Endocrine system Amputations Diaphragm Tumor, generally Breast carcinoma Lung carcinoma Total
1
3
role in the development of the human race from the standpoints of war, commerce, religion, and superstition. He detailed numerous examples of the ubiquitous role of salt in ceremonies, social customs, and barter (the word “salary” comes from solarium, an allowance to Roman soldiers for the purchase of salt). His interest in the southwest again becomes apparent in his references to the place of salt in the early Indian folklore and customs. Dr. Orr was colorful when he was philosophic. At one time (Table III) in 19X1, while speaking to a group of medical students, he portrayed the lives of great men in medical history by accenting their eccentricities or their handicaps or their little-known peculiarities, to make history come alive. He urged students to pick a hero, and added that “to study medicine without your medical hero is to pocket the nut withTABLE PUBLICATIONS
OF DR.
III
ORR WHICH
MIGHT
BE
CLASSIFIED
AS PHILOSOPHIC
Year 1931 1932 1933 1934 1935 1951
Publication A Medical Philosophy Faith in Medicine Is the Family Doctor Passing? Some Problems in the Treatment The Romance of Common Salt Doctors Making Speeches
* See text for descriptions.
of Cancer
63s
Friesen
out investigating the kernel.” In his published thoughts concerning “Faith in Medicine,” he urged young physicians to honor past medical discoveries and to apply the knowledge of their predecessors to the future. In 1933 Dr. Orr was concerned about the inroads made upon the family physician by the trend towards specialization, technology, and legislation. He reasoned, in answer to his question “Is the Family Physician Passing?,” that the intimate and personal care and assurance of the family physician will always be a necessity, as was the priest-physician relationship to the sick in centuries before that. His thoughts concerning “Some Problems in the Treatment of Cancer” were centered largely on education of the lay public and physicians toward a dispelling of the gloom and the fatalistic attitude surrounding the diagnosis of cancer in 1934, a task which was energetically assumed by the American Cancer Society a decade or more later. One of his historical articles had the captivating title of “Was Ambrose Par& a Murderer?” Characteristic of the thoroughness of Dr. Orr, he reviewed the life and times of Ambrose Par& to assess the circumstances surrounding the supposed indictment of Pare as the murderer of Francis II, King of France, in the sixteenth century. Dr. Orr accumulated sufficient data to cast doubt that the ear injection described by malicious enemies as “pouring of poison into the King’s ear” was a murderous act. On the other hand, Dr. Orr recounted an episode in which Pare urged the captain of the French artillery to fire upon a group of camp followers who were a constant source of annoyance to Par& ; the cannon shots killed fifteen or sixteen women ! To return briefly to Dr. Orr’s publications in clinical investigation (Table II), many of us can recall his descriptions of the still enigmatic hepatorenal syndrome. There were five articles on this subject investigated clinically and three articles reporting animal investigation of the syndrome. The first of these articles, with Dr. Ferdinand C. Hellwig, appeared in 1932 with the title, “Traumatic Necrosis of the Liver with Extensive Retention of Creatinine and High Grade Nephrosis.” They had found only one case in the literature to parallel theirs, and they favored a theory that some toxin was elaborated in the liver through hemorrhagic necrosis which acted directly on the kidney to produce tubular necrosis. In 1939 they reported five more cases and came to the same conclusion re-
garding an unknown toxin, but also emphasized the role of hemorrhage, shock, and infection in the syndrome. Dr. Orr added in his discussion of the paper that he was not “prepared to accept this condition wholesale because there are so many other factors to be taken into consideration.” After much study and speculation on his part regarding the so-called heptorenal syndrome, we note that by 1940 the title of an editorial simply asks the still unanswered question, “Is There a Hepato-Renal Syndrome?” It probably is significant that even now, over twenty-five years later, with all our sophisticated investigative tools for liver, renal, vascular, and chemical functions, the answer is still elusive. It is interesting to note that there were only three publications concerning cancer of the breast, yet he had one of the most thorough follow-up systems and had collected much data concerning these patients. Carcinoma of the lung occupied his interest only briefly, if his bibliography is an indication of attention. In his one article on the subject (1938) he stated that “although surgical treatment has been too recent to evaluate, nevertheless pneumonectomy in selected cases offers the only definite hope of cure.” Perhaps the area most recent in our memory of Dr. Orr is in connection with his probing into the question of radical versus palliative procedures for carcinoma of the head of the pancreas. His initial articles on this subject, in 1941, stress the findings of fatty infiltration of the liver in patients operated upon for carcinoma of the head of the pancreas. His first operations were two stage procedures without pancreatic anastomosis to the intestine, which may account for the poor utilization of fat which concerned him. By 1942 he was emphasizing the use of vitamin K and restoring pancreatic drainage to the intestine, and in a period of less than four years he had performed nine radical procedures. In 1945 he published an extensive review of the literature to attempt to answer the question whether radical pancreatoduodenectomy is justifiable, and stated that the data were not very convincing. By 1946 he apparently was convinced because he stated that greater length of life has resulted with the radical operation than with any type of palliative operation. He advocated radical operation for small lesions of the ampulla and duodenum. He urged further study for final evaluation of the radical proceThe American Journal of Surgery
Thomas dure ~7~1,in 1~62, reported that a search of the literature had revealed seventeen patients who had survivetl five years or more after radical pancreatoduodenectomy for carcinoma. By this time he had performed twenty-four of the radical operations without a five year survivor but despite this he continued to advise a one stage radical operation as the most satisfactory palliative procedure. CHANGING
PICTURE
OF CLINICAL
INVESTIGATION
Clinical investigation is as old as medicine itself, if it is implied that investigation consists of detailed observation of the natural course of the disease in patients. Hippocrates and Galen made nlany clinical observations which influenced succeeding physicians for centuries. Ambrose Par& appeared not to be afraid to challenge old ideas with new ones. Lister, when he sa\v the importance of Pasteur’s contributions, made observations of his own regarding the role of antisepsis in surgery. John Hunter, however, was the investigator par excellence in surgical history when he made the observation that nature alone has the power to heal and that the surgeon helps the patient mainly by aiding the natural recovery processes. In addition to the pursuit of clinical phenomena, John Hunter sa\v the advantage of coupling human studieh with animal experimentation. This coupling of investigative efforts reached its peak in the twentieth century. Dr. Orr’s contribution to intestinal obstruction was an example in which studies on patients and on the experimental animal proceeded together. It has been controversial whether one method of investigation is superior to the other; ultimately the investigative idea begins with a clinical problem and hopefully ends with a clinical solution. The methods of reaching that solution, however, sometimes can be accomplished only by appropriately controlled studies in laboratory animals. When it is possible to obtain su&cient data from patients, the investigative aspects of the patient’s disease are, of course, most meaningful, and when in the course of these investigations data are obtained relative to that patient’s disease but which is “over and above” that which is considered pertinent to the immediate managetnent, clinical investigation may be said to be taking place. The collection of data pertinent to a patient’s disease, from the patient himself, is meaningless unless it is accurately recorded and honest Vol.116, November 1968
Grover
Orr
(Cl!)
judgments are made. The most rewarcling practice of surgery involves the discover>- that the observations tnltde in patients lead to new knowledge which can be applied with a greater promise of success in the next patient. “Poorly worked-up” patients often do not yielr! such a satisfying reward for the surgeon and seldom result in a satisfactory experience ior the patient. Whereas much can be learned from patients who are thoroughly and ideally “worked-up.” there are opportunities at the present time when disease processes, metabolic abnormalities, and results of treatment can be investigated in a more sophisticated and controlled manner. I refer to the federally-supported clinical research centers of some institutions. For the first time, appropriate and approved prospective btutlies may be made without involving the patient himself directly with the costs of such studies. The information gained usually has far-reaching benefits not only to the patient so studied but also to many other patients who become the recipients of such advances of thought and skills. My own experience \vith patients admitted to such a clinical research center is that patients readily accept the opportunity for thorough studies, some of which are impractical in an ordinary hospital environment, when they realize the potential benefit to themselves as well as to others. Dr. Orr would be agreeably surprised at the relative ease with which patients can be studied today. As Ire look at the future, we too may be surprised at the mass of data which may accrue when computerized collection of information and recall of all accumulated data become universally applicable. Whether clinical investigation of patients takes place in the usual hospital environment or in a federally-supported unit such as a clinical research center, my own experience indicates that such studies are more accurately and more efliciently accomplished in a unit set up for investigative purposes. For the past three years, I have been using a clinical research center for preoperative studies of patients in whom I expect to perform some type of gastric operation and postoperative studies of patients who have had such operations. Detailed studies of gastric secretory physiology, rdstric motor activity, and pancreatic carbohydrate metabolism are carried out more efficiently and more accurately than in an ordinary hospital environment. This type of thorough study of patients
640
Friesen
having gastric operations may lead to the development of improved operations as well as a clarification of our understanding of the abnormal physiology. In another group of patients with marked hypersecretion of gastric acids associated with endocrine tumors, a thorough evaluation of all endocrine organ functions is more likely to be fruitful in a clinical investigative unit than in an active surgical ward. In the instance of patients having ulcerogenic tumors of the pancreas, clinical studies in eleven patients have yielded the important observation that total removal of the stomach has caused a regression of metastatic nonbeta islet cell carcinoma of the pancreas. Metastases to the lung and liver have visibly disappeared after total gastrectomy. This suggests that a gastric factor plays an important role in the pathogenesis of the Zollinger-Ellison syndrome; moreover, it is suggested that the stomach influences the growth of islet cells of the pancreas.* Studies such as these, which were initiated primarily as a clinical investigation of a select group of patients, have every possibility of leading to broader solutions of clinical importance for a much larger group of patients, such as the elucidation of the causes of the more common duodenal ulcer in man. When clinical investigation is coupled with pertinent controlled laboratory investigation, the evolution of knowledge is hastened. It is acknowledged that thorough investigation is costly in terms of time and money. With the stretching of the American economy at the present time, there is a real concern whether research can continue at its present pace under federal subsidy. One solution to this problem was suggested by Dr. Wangensteen when he honored Dr. Orr upon the latter’s retirement, when he described the growing concept of private support for research. That this is possible is illustrated by the following account. Our recent reports of the gastric influence on islet cell carcinoma prompted a private donor of funds to inquire about the status of funds previ* The clinical investigations referred to here were carried out with the financial support of NIH Grant #FR-67.
ously given to the University of Kansas for cancer research. In this instance, an initial gift of $1,000, followed by one of $1,500, and then by a farm valued at $29,000 (a total gift of $31,500) was reinvested and through a series of judicious transactions, in less than twenty years the monetary value of that gift has increased to $160,000; the value to research may be inestimable. Private donations such as this, augmented by similarly-inclined donors, could have an important influence on the future of clinical investigation. Significant as private support of research may be, such amounts are small compared to the budget of the National Institutes of Health, where the intramural budget is 200 million dollars and the extramural grants and aid total 900 million dollars. The research, both clinical and laboratory, made possible by such federal support, probably is the most significant in the world, but any clinical evaluation and study of patients by any one of us who treat patients is important also. Most of us will do well if we conscientiously keep foremost in our minds that keen observation of our patients usually leads to more successful management, that a “well worked-up” patient usually “does better,” and that we as surgeons will fare more happily knowing that we have done our best and have contributed in our own way to a rapidly expanding field of knowledge. SUMMARY
The influence upon clinical investigation of Thomas Grover Orr, whom we are commemorating in this Memorial Lecture, was a significant one. Through keen observations of patients, he applied new knowledge to clinical problems. When he coupled these studies with laboratory investigations, his impact was even more significant, as with intestinal obstruction. Accomplishment of new knowledge came about most fruitfully when he worked with other established investigators, an illustration of the “team approach” to investigation. His example of thorough study of patients leads us today to use whatever means and facilities we have to further our knowledge through clinical investigation
The American
Jouvnal of Surawy