Research at Ochsner Clinic: Highlights in its History

INTRODUCTION

Dr. Alton Ochsner and his four partners, Dr. Guy Alvin Caldwell, Dr. Edgar Burns, Dr. Francis E. LeJeune, and Dr. Curtis Tyrone, created a new system of delivering health care in the Gulf South that they named the Ochsner Clinic. The Clinic opened its doors on January 2, 1942, and in 2007, after 65 years of existence, continues to provide superb health care regionally, nationally, and internationally. Many publications have dealt with the rich history and success of the Clinic and its founders (1–3). This narrative will focus on how the Clinic's research efforts contributed to its success.

ALTON OCHSNER AND THE FOUNDERS' CONTRIBUTIONS TO RESEARCH

The historical timeline of research at Ochsner Clinic starts with its founders (2). In the summer of 1927 at the age of 31, Alton Ochsner accepted the position as chairman of the Department of Surgery at Tulane University School of Medicine, and succeeded in organizing one of the America's premier surgical teaching programs at Charity Hospital, an institution that provided invaluable clinical and research opportunities to Ochsner and his students. The same drive and interest in research followed Dr. Ochsner and the other founders when they established the Ochsner Clinic. Although a description of his and the other founders' contributions to research is beyond the scope of this narrative, all made important contributions to the growth of their specialties. And although Dr. Ochsner made important innovations in the field of surgery, he will always be remembered because he exposed the hazards of tobacco and its link to lung cancer. In 1939, in a paper published in Surgery, Gynecology and Obstetrics, he and Michael DeBakey reported, “In our opinion the increase in smoking with the universal custom of inhaling is probably a responsible factor, as the inhaled smoke, constantly repeated over a long period of time, undoubtedly is a source of chronic irritation to the bronchial mucosa” (4). His peers criticized him, but his ideas about tobacco prevailed. Four years after Dr. Ochsner's death, Merrell Dow Pharmaceuticals created the Alton Ochsner Award, which is presented annually to individuals and organizations for their efforts to help people stop smoking.

THE ALTON OCHSNER MEDICAL FOUNDATION

The establishment of the Alton Ochsner Medical Foundation was very important in separating Ochsner from other private practice groups, and it paved the way not only for the development of academic programs but also for the growth of research programs. In 1944, the founders wanted to expand the Clinic's activities to include areas of public service. More specifically, they were keen on developing programs in research, medical education, and charity. On the advice of J. Blanc Monroe, the Clinic's attorney, Dr. Ochsner and his colleagues elected to maintain the Clinic for the practice of medicine and established a non-profit foundation to execute all its other activities.

On January 15, 1944, the Alton Ochsner Medical Foundation was chartered. Article II of the charter indicated the reason for its existence: “The general purpose of this corporation shall be scientific, educational, literary and charitable; and to promote medical and surgical and scientific learning, skill, education in the broadest sense; and to add and advance the study and investigation of human ailments and injuries and the causes, prevention, relief and cure thereof, without distinction as to the means of the patient, his race or domicile…to conduct more research, both clinical and laboratory…” (1).

The first director of the newly established Alton Ochsner Medical Foundation was Dr. Dean Echols, who was in charge of educational training programs. In addition, Dr. Thomas Findley, the Head of the Department of Medicine, was appointed as the Director of Research. Through the combined efforts of Dr. Findley and Dr. Echols, Dr. Otto and Mrs. Selma Schales were hired from the Peter Bent Brigham Hospital in Boston to continue their research in chemistry at Ochsner, marking the beginning of the Foundation's research program. The hiring of Dr. Albert Segaloff in 1945 to head research in endocrinology and Dr. Edward D. Frohlich in 1976 to be Vice-president of Education and Research were pivotal in establishing the Clinic as a research institute (1).

OTTO SCHALES

On July 11, 1944, the trustees of the foundation approved the hiring of Dr. and Mrs. Schales as directors of the investigative laboratory for $300 and $200 a month, respectively. They set up the first research laboratory on the second floor of the former Denegre Martin residence (Research Annex) on Prytania Street adjacent to the main clinic building and began doing research in the properties of renin. A $5,000 grant from Smith, Kline, and French, in addition to equipment purchased for $2,100, helped support these studies (1). Several investigators were studying ways of purifying renin and Dr. Schales described one of the methods that was very well-recognized at the time. In 1943 in the Journal of Experimental Medicine, Katzand Goldblatt (5) reported the importance of Dr. Schales' work in elucidating the underlying mechanisms of human hypertension in a seminal paper. The authors wrote, “The elucidation of the humoral mechanism of experimental renal hypertension or of comparable human hypertension will not be complete until the various constituents involved in the mechanism are isolated in pure form. Several methods of preparation and purification of hog renin have been described [including Schales method]….In the main, these methods involve fractionation of the kidney extract with neutral salts.” (5)

Dr. Schales was a member of the American Association of Clinical Chemists and in 1955 he served as its president, as stated in the Association's newsletter dated 1955: “Otto Schales, of the Alton Ochsner Clinic in New Orleans, LA was elected President of the American Association of Clinical Chemists…. Dr. Schales has served the Association in many capacities and was Vicepresident for the past year. He is well known for his scientific and professional attainments.” He was also a founding member of the association's journal, the Journal of Clinical Chemistry, in 1955. (6)

ALBERT SEGALOFF

The extensive involvement of the Ochsner Clinic in the diagnosis and treatment of breast cancer started when Albert Segaloff was hired in 1945 from Wayne State University to head endocrine research (1). While Dr. Segaloff's early work in the 1930s focused on the thymus gland, it shifted later to studying the way estrogens are generated and metabolized. He also contributed to the development of the first human oral contraceptive. His basic work in breast cancer was performed in a strain of rats that he bred, named AXC for the two parent strains: August, a white breed with a black hood, and Copenhagen, a brown nervous breed with black tipped coat. Dr. Segaloff received a research grant from the National Cancer Institute to study low dose irradiation on the mammary gland in these rats. In addition to his work in the basic laboratory, Dr. Segaloff was also a pioneer in the application of research findings to the treatment of patients. In 1951, he published the first paper on the treatment of breast cancer with testosterone and reported that Al-testololactone, a substance synthesized from testosterone by fermentation, produced objective regression in advanced breast cancer despite its lack of hormonal activity (7). He coordinated for one of the first adrenalectomies in 1953, producing a dramatic reduction of a breast tumor.

Dr. Segaloff was recognized internationally for developing a standard for breast tumor measurement. This method was utilized to assess the effectiveness of a treatment modality. He was one of the first to treat adrenal hyperplasia with cortisone and received multiple federal grants to study several aspects of breast cancer. When the newly built research facility was dedicated and named Richard W. Freeman Research Institute in 1974, Dr. Segaloff reminisced about Ochsner Clinic's commitment to developing research: “The founders of the Alton Ochsner Medical Foundation recognized that research had to be an integral part of the outstanding medical institution which their foresight has created here. We came in difficult times and built as well as we could research facilities in the wooden pre-Civil war building behind the original clinic building….Research is an intellectual pursuit well larded with hard and repetitious work but human effort alone is not enough. Our new research facilities gave us superb small animal quarters so that we are now amongst the most expert in the world in aging animals for needed studies in carcinogenesis, endocrine activity….It has been a delight to have the opportunity to work in these superb facilities and I trust that their contribution to medicine will continue to expand.” (8)

When I was a research fellow in hypertension, I had the opportunity to meet Dr. Segaloff in research meetings and he appeared to me very stern and intelligent; he was also very precise in presenting data and made insightful remarks about our presentations of either basic or clinical work.

Dr. Segaloff wrote more than 100 manuscripts in his specialty, edited several journals, and was an important figure not only in the basic understanding of breast cancer but in the multidisciplinary approach to the treatment of the disease. He was a member of national committees to push research forward in breast cancer, and his contributions were integral in attaining an effective treatment of breast cancer. After a brilliant and rewarding career, Dr. Segaloff died in February 1985.

EDWARD D. FROHLICH

Another important appointment to research at Ochsner Clinic was that of Dr. Edward D. Frohlich, who led Education and Research. Dr. Frohlich and his group came from the University of Oklahoma in 1976, which marked the beginning of a very successful and internationally recognized basic and research program in the diagnosis, mechanisms, and treatment of arterial hypertension. Dr. Frohlich is recognized internationally for his investigative work in clinical and experimental hypertension. His clinical studies have included physiological, hemodynamic, and echocardiographic assessment of different clinical forms and severity of hypertensive disease (including elucidation of the natural history of the disease); demonstration of early target organ involvement by the disease; and evaluation and mechanisms of action of new pharmacological antihypertensive entities. His experimental laboratory research work has been concerned with the development of techniques for hemodynamic assessment of experimental forms of hypertension (spontaneously hypertensive and Goldblatt-hypertensive rat models); elucidating heart and kidney involvement in hypertension; and mechanisms of antihypertensive drug actions. From January 1, 1994 through January 1, 2001 he served as editor-in-chief of Hypertension, one of the five major scientific journals of the American Heart Association.

He is an Alton Ochsner Distinguished Scientist and holds academic appointments as Professor of Medicine and Physiology at Louisiana State University Health Sciences Center and Clinical Professor of Medicine and Adjunct Professor of Pharmacology at Tulane University. He has also held appointments as George Lynn Cross Research Professor of Medicine and as Professor of Physiology and of Pharmacology at the University of Oklahoma Health Sciences Center. Dr. Frohlich continues to be very active in education and research.

CONCLUSION

The importance of historical achievements was well described by T.S. Eliot, who wrote “….the historical sense involves the perception not only of the pastness of the past, but of its presence….” (9). In summary, this historical overview highlights some of Ochsner's contributions to the field of research. In other words, one cannot view the present without appreciating its connection to the past. With this in mind, a historical overview of research at Ochsner Clinic is crucial to recognizing not only how far we have come, but also how much we can accomplish in the future.