Skip to main content
SpringerLink
Log in

A Brief History of Clinical Cross-Species Organ Xenotransplantation

  • Chapter
  • First Online:
Clinical Xenotransplantation

Abstract

Cross-species transplantation (xenotransplantation) offers the prospect of an unlimited supply of organs and cells for clinical transplantation, thus resolving the critical shortage of human tissues that currently prohibits a majority of patients on the waiting list from receiving transplants.

Between the seventeenth and twentieth centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the nineteenth century, with grafts from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into elderly men whose “zest for life” was deteriorating, believing that the hormones produced by the testis would “rejuvenate” his patients. Following the pioneering surgical work of Carrel, who developed the technique of blood vessel anastomosis, numerous attempts at nonhuman primate organ transplantation in patients were carried out in the early twentieth century.

In 1963–1964, when human organs were not available and chronic dialysis was not yet in common use, Reemtsma transplanted chimpanzee kidneys into six patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992, he obtained patient survival for 70 days following a baboon liver transplant.

With the advent of genetic engineering and cloning technologies, pigs are currently available with a number of different manipulations that protect their tissues from the human immune response, resulting in increasing pig graft survival in nonhuman primate models. Genetically modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant.

Based on a paper published in Proc (Bayl Univ Med Cent). 2012; 25:49-57, with permission of the editor.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Cooper DKC, Lanza RP. Xeno – the promise of transplanting animal organs into humans. New York: Oxford University Press; 2000. p. 1–274.

    Google Scholar 

  2. Ekser B, Ezzelarab M, Hara H, et al. Clinical xenotransplantation – the next great medical revolution? Lancet. 2012;379:672–83.

    PubMed  Google Scholar 

  3. Taniguchi S, Cooper DKC. Clinical xenotransplantation – past, present and future. Ann R Coll Surg Engl. 1997;79:13–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Deschamps JY, Roux FA, Sai P, Gouin E. History of xenotransplantation. Xenotransplantation. 2005;12:91–109.

    PubMed  Google Scholar 

  5. Reemtsma K. Xenotransplantation – a brief history of clinical experience: 1900-1965. In: Cooper DKC, Kemp E, Reemtsma K, White DJG, editors. Xenotransplantation: the transplantation of organs and tissues between species. 1st ed. Heidelberg: Springer; 1991. p. 9–22.

    Google Scholar 

  6. Gibson T. Zoografting: a curious chapter in the history of plastic surgery. Br J Plast Surg. 1955;8:234–42.

    CAS  PubMed  Google Scholar 

  7. Cooper DKC. Xenografting: the early, early years. Xeno. 1997;5:21–2.

    Google Scholar 

  8. Roux FA, Dai P, Deschamps J-Y. Xenotransfusions, past and present. Xenotransplantation. 2007;14:208–16.

    PubMed  Google Scholar 

  9. Smood B, Bottino R, Cooper DKC. Xenotransplantation of the endocrine pancreas. In: Orlando G, Gruesner R, Piemonti L, Stratta R, Ricordi C, editors. Transplantation, bioengineering, and regeneration of the endocrine pancreas, vol. 1–2. New York: Elsevier/Academic Press; 2019.

    Google Scholar 

  10. Hara H, Cooper DKC. The immunology of corneal xenotransplantation: a review of the literature. Xenotransplantation. 2010;17:338–49.

    PubMed  Google Scholar 

  11. Hara H, Cooper DKC. Xenotransplantation – the future of corneal transplantation? Cornea. 2011;30:371–8.

    PubMed  PubMed Central  Google Scholar 

  12. Hamilton D. The first transplant surgeon: the flawed genius of Nobel prize winner, Alexis Carrel. London: World Scientific Publishing; 1986.

    Google Scholar 

  13. Real J. Voronoff. (French). Paris: Editors Stock; 2001.

    Google Scholar 

  14. Voronoff S. Rejuvenation by grafting. New York: Adelphi; 1925.

    Google Scholar 

  15. Hamilton D. The monkey gland affair. London: Chatto and Windus; 1986.

    Google Scholar 

  16. Matevossian E, Kern H, Hüser N, et al. Surgeon Yurii Voronoy (1895-1961) – a pioneer in the history of clinical transplantation: in memoriam at the 75th anniversary of the first human kidney transplantation. Transpl Int. 2009;22:1132–9.

    PubMed  Google Scholar 

  17. Lee RA. The bizarre careers of John R. Brinkley. Lexington: University Press of Kentucky; 2002.

    Google Scholar 

  18. Sgroi A, Buhler LH, Morel P, Sykes M, Noel L. International human xenotransplantation inventory. Transplantation. 2010;90:597–603.

    PubMed  Google Scholar 

  19. Reemtsma K, McCracken BH, Schlegel JU, et al. Renal heterotransplantation in man. Ann Surg. 1964;160:384–410.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Starzl TE, Marchioro TL, Peters GN, et al. Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation. 1964;2:752–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Küss R. Human renal transplantation memories, 1951-1981. In: Terasaki PI, editor. History of transplantation: thirty-five recollections. Los Angeles: UCLA Tissue Typing Laboratory; 1991. p. 37–59.

    Google Scholar 

  22. Hardy JD, Chavez CM, Kurrus FD, et al. Heart transplantation in man: developmental studies and report of a case. JAMA. 1964;188:1132–40.

    CAS  PubMed  Google Scholar 

  23. Cooper, D.K.C., Ye, Y. Experience with clinical heart xenotransplantation. In: Xenotransplantation: the transplantation of organs and tissues between species. 1st edition. Cooper, D.K.C., Kemp, E., Reemtsma, K., White, D.J.G. (eds). Springer; Heidelberg, 1991, pp. 541–557.

    Google Scholar 

  24. Barnard CN. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J. 1967;41:1271–4.

    CAS  PubMed  Google Scholar 

  25. Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J. 1977;52:1035–8.

    CAS  PubMed  Google Scholar 

  26. Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA. 1985;254:3321–9.

    CAS  PubMed  Google Scholar 

  27. Starzl TE, Marchioro TL, Faris TD, McArdle MJ, Iwasaki Y. Avenues of future research in homotransplantations of the liver. Am J Surg. 1966;112:391–400.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Starzl TE. Orthotopic heterotransplantation. In: Starzl TE, editor. Experience in hepatic transplantation. Philadelphia: W.B. Saunders; 1969. p. 408.

    Google Scholar 

  29. Starzl TE, Ishikawa M, Putnam CW, et al. Progress in and deterents to orthotopic liver transplantation, with special reference to survival, resistance to hyperacute rejection, and biliary duct reconstruction. Transplant Proc. 1974;6:129–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Giles GR, Boehmig HJ, Amemiya H, Halgrimson CG, Starzl TE. Clinical heterotransplantation of the liver. Transplant Proc. 1970;2:506–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Starzl TE, Fung JJ, Tzakis A, et al. Baboon-to-human liver transplantation. Lancet. 1993;341:65–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Makowka L, Cramer DV, Hoffman A, et al. The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure. Transplantation. 1995;59:1654.

    Google Scholar 

  33. Makowka L, Wu GD, Hoffman A, et al. Immunohistopathologic lesions associated with the rejection of a pig-to-human liver xenograft. Transplant Proc. 1994;26:1074–5.

    CAS  PubMed  Google Scholar 

  34. Abouna G. Extracorporeal xenogeneic liver perfusion for the treatment of hepatic failure. In: Cooper DKC, et al., editors. Xenotransplantation. 2nd ed. Heidelberg: Springer; 1997.

    Google Scholar 

  35. Groth CG, Korsgren O, Tibell A, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet. 1994;344:1402–4.

    CAS  PubMed  Google Scholar 

  36. Cooper DKC, Gollackner B, Sachs DH. Will the pig solve the transplantation backlog? Ann Rev Med. 2002;53:133–47.

    CAS  PubMed  Google Scholar 

  37. Cooper DKC, Novitzky D, Wicomb WN. The pathophysiological effects brain death on potential donor organs, with particular reference to the heart. Ann R Coll Surg Engl. 1989;71:261–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Novitzky D, Wicomb WN, Cooper DKC. Pathophysiology of brain death and effects of hormonal therapy in large animal models. In: Novitzky D, Cooper DKC, editors. The brain-dead organ donor: pathophysiology and management. Springer: Heidelberg; 2012. p. 65–90.

    Google Scholar 

  39. Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med. 1997;3:282–6.

    CAS  PubMed  Google Scholar 

  40. Onions D, Cooper DKC, Alexander TJ, et al. An assessment of the risk of xenozoonotic disease in pig-to-human xenotransplantation. Xenotransplantation. 2000;7:143–55.

    CAS  PubMed  Google Scholar 

  41. Takeuchi Y, Fishman J. Long life with or without PERV. Xenotransplantation. 2010;17:429–30.

    PubMed  Google Scholar 

  42. Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006;12:301–3.

    CAS  PubMed  Google Scholar 

  43. Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12:304–6.

    CAS  PubMed  Google Scholar 

  44. van der Windt DJ, Bottino R, Casu A, et al. Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant. 2009;9:2716–26.

    PubMed  Google Scholar 

  45. Dufrane D, Goebbels RM, Gianello P. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation. 2010;90:1054–62.

    PubMed  Google Scholar 

  46. Bottino R, Bottino R, Wijkstrom M, et al. Pig-to-monkey islet xenotransplantation using multi-transgenic pigs. Am J Transplant. 2014;14:2275–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Shin JS, Kim JM, Kim JS, et al. Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant. 2015;15:2837–50. Erratum in: Am J Transplant. 2016; 16:1941.

    CAS  PubMed  Google Scholar 

  48. Elliott RB. Towards xenotransplantation of pig islets in the clinic. Curr Opin Organ Transplant. 2011;16:195–200.

    CAS  PubMed  Google Scholar 

  49. Martin C, Plat M, Nerriére-Daguin V, et al. Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Res. 2005;14:373–84.

    CAS  PubMed  Google Scholar 

  50. Lévêque X, Cozzi E, Naveilhan P, Neveu I. Intracerebral xenotransplantation: recent findings and perspectives for local immunosuppression. Curr Opin Organ Transplant. 2011;16:190–4.

    PubMed  Google Scholar 

  51. Vadori M, Aron Badin R, Hantraye P, Cozzi E. Current status of neuronal cell xenotransplantation. Int J Surg. 2015;23:267–72.

    PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks the editor of the Proceedings of the Baylor University Medical Center for permission to reproduce sections of his published paper. Work on xenotransplantation in the author’s laboratory in the Department of Surgery at the University of Alabama at Birmingham has been supported in part by NIH grants U01 AI068642, R21 AI074844, and U19 AI090959, and by Sponsored Research Agreements between the UAB and United Therapeutics, Silver Spring, MD.

Author information

Authors and Affiliations

  1. Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    David K. C. Cooper

  2. Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    David K. C. Cooper

Authors
  1. David K. C. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David K. C. Cooper .

Editor information

Editors and Affiliations

  1. Xenotransplantation Program, University of Alabama at Birmingham, Birmingham, AL, USA

    David K. C. Cooper

  2. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    Guerard Byrne

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cooper, D.K.C. (2020). A Brief History of Clinical Cross-Species Organ Xenotransplantation. In: Cooper, D.K.C., Byrne, G. (eds) Clinical Xenotransplantation. Springer, Cham. https://doi.org/10.1007/978-3-030-49127-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-49127-7_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-49126-0

  • Online ISBN: 978-3-030-49127-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation