First baboon to human liver
transplant
PITTSBURGH, June 29, 1992--Surgeons from the University of Pittsburgh
Medical Center (UPMC) announced on June 29, 1992, that they transplanted a liver from a
baboon into a 35-year-old male. The 11-hour operation, which began at Pitt's Presbyterian
University Hospital at 11:24 a.m. on June 28, marks the first known baboon-to-human liver
transplant in the world.
The surgery was performed by Satoru Todo, M.D., Andreas Tzakis, M.D., and John Fung,
M.D., Ph.D., who are members of the Pitt transplant team under the direction of pioneer
transplant surgeon Thomas E. Starzl, M.D., Ph.D. Twenty-nine years ago, Dr. Starzl was
among the first to use animal organs in humans.
The recipient of the cross-species transplant, also called a xenotransplant, is a
patient with chronic, active hepatitis B, a liver disease that will lead to death as it
progresses.
Hepatitis B is considered by many members of the transplant community to be an absolute
contraindication for liver transplantation because of the great likelihood the disease
will recur in the newly transplanted liver.
"Baboons cannot be infected with hepatitis B, so as sources for organs, they may
offer a solution for these patients," said Dr. Starzl, director of Pitt's
Transplantation Institute.
"The baboon offers a distinct advantage to the patient with hepatitis B -- a
chance to live. For all transplant candidates, xenotransplantation with organs from
baboons or other animals can offer a predictable, ready supply of organs. This would, in
turn, result in fewer patients dying while waiting and allow us to operate on an elective
basis, before patients are literally at death's door," claimed Dr. Starzl.
"An animal organ may also be used as a temporary measure to sustain life until a
human donor is available," added Satoru Todo, M.D., an associate professor of
surgery.
Xenotransplantation has long been considered an answer to the critical shortage of
available human donor organs. While patient waiting lists have become longer, the
inadequate supply of donor organs persists. Nationwide, at least one patient dies each day
while waiting for a liver transplant, and this figure has increased each year.
According to Dr. Starzl, recent research advances, particularly those related to drugs
which interact with the immune system, have enabled his team to perform the operation.
"For the despairing liver transplant candidates at Pitt and elsewhere, the timing
of these developments is a Godsend," Dr. Starzl said.
"Combatting rejection, especially in a xenotransplant model, is the ultimate
challenge faced by those engaged in transplantation research. We believe we now have an
effective combination of drugs capable of suppressing the recipient's immune system so
that the foreign, animal organ is not rejected," added Dr. Fung, chief of
transplantation at Pitt, referring to the drugs FK506, cyclophosphamide, prostaglandin,
and prednisone.
FK506, a drug manufactured by Fujisawa Pharmaceutical Co., Ltd., of Japan and developed
at Pitt to combat rejection, works to suppress the recipient's T-cells from attacking the
donor organ. T-cells are one type of white blood cell important to the immune system.
Cyclophosphamide, a Bristol-Myers Squibb drug developed to treat cancer, was shown to
hold promise for transplant recipients by Dr. Starzl more than 20 years ago. Commercially
known as Cytoxan, cyclophosphamide prevents B-cells, another type of white blood cell,
from proliferating, a process which occurs in the presence of an antigen -- a foreign
substance -- and results in the production of antibodies. Antibodies help destroy the
foreign substance.
Prednisone is a steroid hormone that affects those cells which help recognize and
process antigens, while prostaglandin serves to subdue the chain reaction of events likely
to occur in the immune system.
Collectively, these contain the forces that can prevent both forms of rejection from
occurring: cellular rejection, which involves T-cells; and humoral rejection, when B-cells
activate the production of antibodies. Early rejection in xenotransplantation primarily
involves the humoral response and can be rapid and uncontrollable if the recipient has
natural antibodies to another species' antigens. Pitt researchers conducted laboratory
studies which found no natural antibodies specific to baboon antigens in the human immune
system.
"Another point in our favor is the liver itself. In humans, we have found the
liver to be more resistant to humoral rejection than any other organs which are
transplanted. So, the main obstacle in xenotransplantation is lessened for the
liver," said Dr. Tzakis, formerly an associate professor of surgery at the UPMC.
Prior to performing the surgery, the Pitt transplant program received the approval from
the university's Institutional Review Board and Animal Use Committee and advised the Food
and Drug Administration of its intent.
The baboon was selected as a source because it is not an endangered species, and can be
bred safely and easily in captivity.
Although early attempts at xenotransplantation date back as far as 1905, new
understanding of the immune system and subsequent new drugs created the scientific climate
for several attempts in the 1960s, at a time when both dialysis treatment and cadaver
organs were not widely available. In 1963 and 1964, Keith Reemtsma, M.D., performed
chimpanzee-to-human kidney transplants in 12 adults at Tulane University. One recipient
lived with the kidney for nine months without evidence of rejection before dying of an
infection. Soon after this series, other surgeons made unsuccessful attempts to transplant
a chimpanzee heart and kidney, and Dr. Starzl performed kidney transplants in six adults
using baboon donors. The patients lived for 19 to 98 days after their transplants. Between
1969 and 1974, Dr. Starzl provided chimpanzee livers to three children, one of whom lived
14 days before succumbing to sepsis, a widespread infection. Surgeons at Loma Linda
University had available the anti-rejection drug cyclosporine when Baby Fae received a
baboon heart in 1984. The infant died of rejection 20 days after surgery. Between 1963 and
1984, 28 clinical procedures involving solid organs from animal donors were performed in
the United States and South Africa.
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MEDIA CONTACT: Lisa Rossi
Tel: (412) 647-3555 Fax: (412) 624-3184
EMAIL: ROSSIL@MSX.UPMC.EDU
