CLINICAL XENOTRANSPLANTATION: PATHWAYS AND PROGRESS IN THE TRANSPLANTATION OF ORGANS AND TISSUES BETWEEN SPECIES Cooper David K.C., Byrne Guerard, Basel, Switzerland: Springer International Publishing, 2020, 306 pages

Abstract

The field of organ xenotransplantation has had its ups and downs over the last few decades but has finally reached the point at which clinical trials are being seriously considered. In March 2019, a workshop to address the path forward for porcine kidney and heart clinical xenotransplantation was held at the University of Alabama at Birmingham, a major center of xenotransplantation research. This book is an edited compilation of presentations given at the workshop by experts from relevant scientific, medical, regulatory, and ethical spheres. In general, the book is successful in its stated aim of providing “a pathway to clinical xenotransplantation,” although it is not without shortcomings. One of the book’s strengths is the breadth of topics covered, with 22 chapters divided into seven parts. Parts II–VI (chapters 5–21) are directly based on workshop sessions. Part II outlines the current state of play in preclinical pig-to-nonhuman primate models, addressing the critical question of whether pig kidneys (chapter 5) and hearts (chapter 6) will be capable of doing the job in humans. Part III describes the generation of gene-edited donor pigs with multiple genetic modifications (chapter 7) and gives a useful firsthand example of the regulatory and practical requirements for their housing (chapter 8). Part IV (chapters 9–12) asks what lessons might be learned from antibody-mediated allograft rejection, although the focus can be inconsistent: chapter 9 clearly outlines and discusses the similarities between xenotransplantation and allotransplantation, whereas chapter 11 (while comprehensive and well written) does not mention xenotransplantation until the final page. Part V (chapters 13–18) moves into the contentious area of the evaluation and selection of patients for the first clinical trials. This includes an interesting exploration of the selection of pediatric patients for initial trials of cardiac xenotransplantation (chapter 16)—a delicate issue since the failed baboon heart transplant into “Baby Fae” in 1983. The chapter on infection in xenotransplantation (chapter 17) is of obvious importance, although it seems misplaced in Part V because it concentrates more on donor screening and posttransplant monitoring than patient selection. Part VI (chapters 19–21) addresses the regulatory, economic, and social aspects of xenotransplantation. Chapter 19 gives a brief FDA perspective on the key issues that must be addressed in a first-in-human clinical trial. Chapter 20 (“A Payer’s Perspective”) looks beyond clinical trials to speculate on the possible impact of xenotransplantation on the health-care costs associated with end-stage organ failure. Chapter 21 discusses the important issue of public perception and acceptance, which is arguably an underappreciated consideration in the planning of clinical trials of organ xenotransplantation and beyond. On this point, the allusion to George Orwell’s Animal Farm on page 23, even if tongue-in-cheek, is perhaps a little unwise. Finally, Part VII (chapter 22) is a nicely written summation of what the workshop achieved. The book has some weaknesses. First, the introductory Part I is far too long. It contains four chapters, all of which are based on previous publications. Chapter 1 is a historical review of clinical xenotransplantation that is interesting but could easily have been omitted; while it is important to look to the past, this book is essentially about the future. Chapter 2 (a review of results from pig-to-primate models) is the largest chapter in the book, and chapters 3 and 4 (both about sensitization) seem somewhat out of place. A single introductory chapter giving a concise background and referring to appropriate well-chosen reviews would have been preferable. Second, the book is quite strongly US-centric, and 18 of the 69 listed contributors (26%) are from a single US company. This probably reflects the fact that a large proportion of xenotransplantation research and commercial activity is based in the United States. Nevertheless, there are some areas in the book that would benefit from greater balance. While the book will mainly appeal to those already in the field of xenotransplantation, it should also be of interest to clinicians and scientists in the transplant community who want to know “how close” and “what remains to be done.” The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.