However, it was only the tip of Groth’s Colorado iceberg. His supporting studies in dogs resulted in improved liver preservation and standardization of antilymphoid globulin (ALG), demonstrated the dramatic decline of hepatic blood flow caused by liver rejection and established that transplantation of lymphoid tissues corrected canine hemophilia. His clinical reports included the first descriptions of the value of scintography in liver transplantation, the first correction by liver replacement of an inborn error (Wilson’s disease), the first successful human parathyroid alloengraftment, and the efficacy of “triple-drug” immunosuppression with azathioprine, prednisone, and ALG.
Similar high level innovations continued after Groth’s permanent return to Stockholm in 1972. All were thematic. The foremost continuous theme was organ transplantation, with particular focus on the pancreas. This included his initially controversial advocacy of today’s accepted enteric drainage of pancreatic exocrine secretions. His book Pancreas Transplantation, published in 1988, was the first of its kind and provided crucial incentives for continuation of such efforts. His demonstration that pancreas transplantation ameliorated diabetic complications was years ahead of its time. A second theme was improvement of immunosuppression. He was chief investigator for multinational clinical studies of cyclosporine, tacrolimus, mycophenolate mofetil, and sirolimus (including the first use of sirolimus as the baseline agent). A third theme was cell transplantation. After showing the viability of ectopically transplanted rat hepatocytes (in 1974), he corrected rat glucuronyl transferase deficiency with liver cells (in 1977) and ultimately delineated human inherited disorders that were correctable by bone marrow cells, beginning with Gaucher’s disease. A related fourth theme was transplantation of pancreas islet xenografts, which culminated in an historical pig to human trial of 10 patients with islet survival and C-peptide secretion >1 year.
The quantity and quality of these contributions suggest a superhuman effort. It should be added that Groth also had very real human qualities, best exemplified by a few revealing photographs (Figs. 1–3). May I present Professor Carl Gustav Groth.
Starzl, Thomas E.
Transplantation: December 27, 2006 - Volume 82 - Issue 12 - p 1572-1573
In a recent Commentary in Xenotransplantation, Philip O'Connell outline the challenges of pig-to- human islet transplamation (Tx). His emphasis is on the prevention of the xenogeneic immune reaction. In the present Commentary, we attempt to provide a road map toward clinical pig islet Tx.
The production of a standardized human anti-lymphocyte globulin (ALG) has been hampered by the unavailability of a standard antigen for immunization, and by the finding that most immunization schedules produce variable results in different animals of a given species. In the present study it was found that horses immunized with cultured human lymphoblasts in a schedule of “maximum stimulation”, all developed a very similar antibody response.
There have been 9 reported attempts of orthotopic homotransplantation of the human liver—7 in Denver and one each in Boston11 and Paris. Survival time was 0 to 23 days. There were multiple reasons for death in each case, but in most an important factor was either the failure to obtain good immediate liver function or the inability to subsequently maintain such function.