Solid organ transplantation must certainly be considered one of the most important advances in medicine in the twentieth century. Progress in the field has come from prodigious efforts in the basic science laboratory coupled with bold clinical research endeavors. A full appreciation of how the field has advanced to its current iteration requires knowledge of the earliest breakthrough scientific ideas that have been the foundation for the translational developments that have been applied in the clinic to save the lives of countless individuals.
Ray D. Owen, a totemic figure among pioneering transplant immunologists, is memorialized in this monograph on the anniversary of his birth 100 y ago.
What he accomplished that is so deserving of these collective pieces largely pertain to his research efforts in the 1940s that were among the earliest and most impactful observations of a pathway of acquired immunological tolerance that is showing impressive results in clinical transplant trials of today. That term, “acquired immunological tolerance,” beautifully discussed in Brent's, “A History of Transplantation Immunology,” is defined as a state of specific unresponsiveness to donor immunogens that can be established by the introduction of allogeneic cells into immunologically disparate hosts.Citation1
Thus, the real tolerance story starts with Owen, working at the time in the Department of Genetics at the University of Wisconsin – Madison. His remarkable observations, immortalized in his Science publication describing mixed blood group chimeras of dizygotic Freemartin twin cattle, and the mechanism of the phenomenon via the natural exchange of blood via a shared placenta, opened a door through which subsequent Nobel awarded milestone achievements of Billingham, Brent and Medawar emerged, and directly to our current clinical tolerance induction protocols.
A second, less well-known but perhaps equally ground-breaking an observation by Owen, is also commemorated in this special issue—cross-generational fitness, or the immunologic protection from premature fetal loss of grand-offspring imparted by maternal, non-inherited antigens. Sing-Sing Way and colleagues, who in 2015, <1 y after Ray's death, validated his controversial discovery using an elegant murine model, pay tribute here to his PNAS paper on Rh- daughters of Rh+ women. Ray concluded the 1954 publication with these typically humble words, “Presentation of this hypothesis here, on the basis of admittedly limited data, is justified in the hope that others in a position to test it will be encouraged to do so.”
His presence of mind is still felt in his writings, as, for example, in the Foreword of Brent's brilliant aforementioned tome. Owen states, “At intervals, thoughtful people are impelled to take stock of science or one of its branches, to ask where we are, how we got here, and where are we going.”
The symmetry is almost poetic. We illuminate the legacy of Owen's work in this special issue of Chimerism, beginning with an inspiring history of the precise nature and scope of his seminal work, and through to descriptions of the most contemporary aspects of clinical transplantation tolerance induction experience in the world. The journey has been long and the best is still to come.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
References
- A History of Transplantation Immunology. ed. Brent LC. Academic Press; 1997.