Paratransplantation and Tissue Therapy

Abstract

PARATRANSPLANTATION AND TISSUE THERAPY R. E. BILUNGHAM AND W. B. NEAVES* Introduction "To supply the defects of Nature" was, according to Ambroise Paré in the sixteenth century, "proper to the duties of a chirurgian." Death, illness, and disability of various kinds frequently result from disease or injury involving an organ of the body. In the case of paired organs, loss or a functional shortcoming ofone may be naturally compensated by the other assuming an additional load. In the special case of endocrine glands, life can be sustained by administration ofappropriate hormones. It has been argued, however, that the interests of the patient might be better served by means of a living allograft if simple, innocuous means were available to control the host response on an immunologically specific basis. Currently, for the major internal organs and for certain tissues such as bone marrow, the only generally available treatment for loss or failure is allotransplantation with its attendant, and by no means satisfactorily resolved, problems of tissue typing and immunosuppression to assuage host resistance. The modern clinical application of organ transplantation, largely the outcome of interactions between surgeons and basic scientists over the past 25 years, originated from critical analyses of the failures of early empirical attempts atorgan and tissue replacement and, with their understanding , the development of means of controlling host resistance. Modern endocrinology, including hormone replacement therapy, also had its origins in transplantation, since the classical criterion for ascribing endocrine function to an organ is that replacement away from its normal vascular and nervous connections must successfully correct specific deficiencies brought about by removal of the organ. Most of the pioneering studies in transplantation biology and endocrinology were conducted within the first 2 decades of the present century , and there was little interaction between the investigators pursuing ?Department ofCell Biology, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. We thank Dr. Blair O. Rogers for his helpful advice.© 1979 by The University of Chicago. 0031-5982/79/2203-0061$01.00 320 I R. E. Billingham and W. B. Neaves ¦ Paratransphntation these evolving lines of study which have recently exerted such a tremendous impact on modern medicine and biology. A third, now scarcely recognized derivative that emerged from this ancestry is a discipline, or perhaps more realistically a "cult," that is normally designated "tissue or cell therapy." On the basis of extremely weak experimental underpinnings, its clinical application came prematurely and extended rapidly as a consequence of outrageous therapeutic claims. These soon led to its neglect by orthodox medicine. The principal reviewers of this subject as well as its most vigorous proponents have been lay writers. Today, laymen are probably much better informed about this topic than the clinicians who care for them. The purpose of this article is to review the origins, development, and current status of paratransplantation and tissue therapy, obscure relics representing a primordial branch of transplantation biology that has persisted virtually unchanged for more than half a century, sustaining itself on outmoded principles while remaining uninfluenced by relevant developments in related fields of biomedical science. Testicular Transpfantation The undoubted pioneer in the story of therapeutic testicular transplantation was the renowned physiologist and neurologist, Charles Edouard Brown-Séquard [1], who held many academic posts, including a chair at Harvard, and who ultimately succeeded Claude Bernard as professor of experimental medicine at the Collège de France. Brown-Séquard was the first person to show that animals died if their adrenal glands were removed, and his studies on the function of these organs, published in 1856, established him as a founder of modern endocrinology. In 1889, when Brown-Séquard was 72 years old, he postulated that the testes are the source of an active, invigorating agent that might be obtained from animals and used to rejuvenate men. He was convinced that, at least in part, diminution in testicular function was responsible for the feebleness of old men and suggested that prompt rejuvenation with regard to their mental and physical capabilities would result if sperm could be injected into their veins. After preliminary trials in rabbits, which appear to have established the harmlessness of testicular extracts, Brown-Séquard...