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Transplant innovation and ethical challenges: What have we learned?

A collection of perspectives and panel discussion
November 2, 2008|Cleveland Clinic Journal of Medicine
Denton A. Cooley, MD;John J. Fung, MD, PhD;James B. Young, MD;Thomas E. Starzl, MD, PhD;Mark Siegler, MD;Pauline W. Chen, MD
Author and Disclosure Information

Denton A. Cooley, MD
Founder, President, and Surgeon-in-Chief, Texas Heart Institute, St. Luke’s Episcopal Hospital, Houston, TX

John J. Fung, MD, PhD
Chairman, Departments of General Surgery and Hepato-pancreatic-biliary Surgery; and Director, Transplantation Center, Cleveland Clinic

James B. Young, MD
Chairman, Endocrinology and Metabolism Institute; Director, Kaufman Center for Heart Failure; and Chairman, Academic Department of Medicine, Cleveland Clinic

Thomas E. Starzl, MD, PhD
Distinguished Service Professor of Surgery, University of Pittsburgh School of Medicine, and Director Emeritus, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA

Mark Siegler, MD
Lindy Bergman Distinguished Service Professor of Medicine and Surgery; Director, MacLean Center for Clinical Medical Ethics, University of Chicago, IL

Pauline W. Chen, MD
Bestselling author of Final Exam: A Surgeon’s Refections on Mortality (Vintage 2008) and a transplant surgeon most recently on faculty in the Division of Liver and Pancreas Transplantation, University of California, Los Angeles.

All authors reported that they have no financial interests or relationships that pose a potential conflict of interest with this article.

This article was developed from an audio transcript of the panelists’ presentations and a panel discussion. The transcript was edited by the Cleveland Clinic Journal of Medicine staff for clarity and conciseness, and was then reviewed and revised/approved by each of the panelists and the moderator.

Despite the odds, the transplant field has progressed rapidly

By John J. Fung, MD, PhD

Dr. Pauline Chen’s clinical vignette [see previous article in this supplement] unfortunately still typifies small bowel transplantation. One would not expect to hear that kind of story today for a kidney or liver transplant, but in the early 1970s it was typical.

‘WHY WOULD ANY YOUNG PHYSICIAN WANT TO GET INVOLVED IN THIS?’ 

Dr. Cooley’s comments about the moratorium on cardiac transplantation brought back memories for me, particularly from when I was studying liver transplantation in the 1970s. There was almost uniform mortality in transplants performed in the late 1960s and early ’70s. One wonders why any young physician would have wanted to get involved in transplantation at that time. I was a fellow training with Dr. Thomas Starzl at the University of Pittsburgh and remember him saying, “Just make it work, then let everybody else figure out why.” I think that typifies the surgical mentality.

We perform transplantations because we know that the alternative is prolonged morbidity and death. Knowing that we can provide a touch of hope is why we move forward in this field.

The technology of transplantation has developed through aggressive scientific developments in the laboratory. It is fascinating that all this has developed in only 50 years. If we had proceeded in a very stepwise manner, we probably would not be even a tenth as far along in the field as we are now.

Heart, lung, liver, and kidney transplantation are now all pretty routine. Intestinal transplantation is in the developing phase. The Cleveland Clinic is currently involved in facial transplantation, which has some different ethical issues related to identity.

Everything in transplantation relates to ethics, from issues about using marginal donor grafts or using beating-heart donors when someone has not been declared brain dead, to issues in patient selection, which often depends on social, economic (ie, insurance coverage), and psychosocial factors such as substance abuse and nonadherence issues.

ETHICAL INSIGHTS FROM TRANSPLANTS IN HIV-POSITIVE PATIENTS

An ethical area of particular interest to me that the Cleveland Clinic has also been involved with is transplanting patients who are HIV-positive. This has always been an enigma: why would we want to transplant an HIV-positive patient? Before the advent of antiviral therapies for HIV in the mid-1990s, mortality rates were very high, with patients suffering miserable deaths from Kaposi sarcoma, the JC virus leukoencephalopathies, and other debilitating opportunistic infections.

When I first arrived at the University of Pittsburgh as a fellow, Dr. Starzl was telling us about this mystery virus disease; when they retrospectively analyzed specimens from organ recipients and donors, they realized that HIV was being transmitted to patients from donors as well as from blood transfusions. The exposure to health care providers was also substantial: an average of 20 to 30 units of blood was used for a liver transplant.

Patients who were HIV-positive were excluded from transplants even through the mid-1990s. I remember evaluating standard listing criteria for transplant recipients at a conference and hearing transplant surgeons say that HIV is an absolute contraindication to transplant. I said, “Wait a minute, this is 1997; you cannot say that. Given that attitude, patients with HIV will never be transplanted.” The New England Journal of Medicine had just published a major paper about the extent of survival in patients being treated with highly active antiretroviral therapy.

So we then started a prospective study of transplantation in HIV-positive patients, and long-term follow-up has shown that these patients can do very well. Interestingly, transplantation offers a new approach to treating HIV-positive patients, in terms of immune reconstitution and the ability of immunosuppressive agents to restore immune competency by preventing the T-cell apoptosis initiated by HIV infection.

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