Xenotransplantation of the Pancreas: A Reality Check of Its Historical Emergence

Abstract

Recent advancements being made in the humanization of Crispr-based gene-edited animals have now provided a sophisticated molecular platform for exogenic organ production and xenotransplantation. Although this amazing and novel medical step into the future holds significant therapeutic promise for pancreas xenotransplantation presently impeded by lack of sufficient donors, its origins arose in an era that is often portrayed as an age of medical quackery and iatrogenesis. The present study reexamines the historical and cultural context in which the first pancreatic xenografts which preceded any attempt at allotransplantation emerged as an interventional force within clinical medicine during the mid-1800s into the early part of the 1900s. More specifically, it focuses on the advances and scientific findings that arose historically as a consequence of the newly diagnosed state of diabetes mellitus in the mid-1800s. Known throughout previous centuries yet ever evasive as a defined dysfunctional complex within carbohydrate metabolism, diabetes was initially challenged by its tenuous association with the pancreas. Once correlated however, dynamics were set into motion whereby the then current theory of internal secretion would initiate a struggle between hormone replacement theory per se and organ replacement. Initially the isolation and application of the potential anti-diabetic factor took the form of crude preparations of pancreatic ‘juice’ or the application of raw animal pancreas both via oral consumption as well as xenogeneic grafting. Both interventions proved ineffective. Ultimately the more refined extracts derived from duct-ligated pancreas to reduce the contaminating exocrine parenchyma led to the isolation and therapeutic use of insulin. The historical backdrop provides an insight to legitimate concerns of physicians for patients balanced by their willingness to employ unknown and novel treatments to rescue patients from the dreaded consequences of diabetes. Keyword Diabetes, Pancreas, Xenotransplantation, Insulin, Islets, Internal secretion HistoriCal analysis