Graft and Host, Together Forever.

Graft and Host, Together Forever.

Thomas E. Starzl pioneered organ transplantation with antirejection
drugs—an approach he hopes to end through a phenomenon called
microchimerism
By MARGUERITE HOLLOWAY.

The dogs bound into the office, two of them. Not quite Hounds of the
Baskervilles, but large enough. It is a dramatic lead. A minute or
so later Thomas E. Starzl follows them in, and, while his pets nap
and his assistant provides this or that document or letter, he
settles in to recount a story, a compelling narrative of a field
that has come full circle. All the classical elements are there: a
missed turn, bad timing, a paradigm shift, some overturned dogma and
a satisfying, hopeful conclusion: organ transplantation without a
lifetime of antirejection drugs.

The 80-year-old Starzl, a transplant surgeon and researcher at the
University of Pittsburgh, where he has an institute named after him,
is legendary for his groundbreaking work over the past five decades.
He was the first person to perform human liver transplants. He
developed new techniques for transplant surgery, helped to make
kidney transplantation viable and was one of the first researchers
to try xenografts—in the 1960s he placed baboon kidneys in six
patients. (None of the transplants lasted long.)

Crucially, he experimented with, combined and developed drugs to
suppress the immune system, thereby preventing organ rejection. He
advocated widespread use of these immunosuppressants, and because of
these drugs, the number of transplants has grown every year for the
past several decades; in 2005 surgeons performed 28,107 transplants
of the kidney, liver, pancreas, heart, lung and intestine, according
to the United Network for Organ Sharing. But although the drugs
permit transplants and save lives, they also have debilitating and
sometimes deadly side effects, because the weakened immune system
cannot fight viruses or cancers. Transplant specialists have
considered the chemicals to be a necessary evil: freed from their
dampening influence, the patient's immune system would rebound and
reject the foreign organ.

In 1992 Starzl observed something that convinced him to rethink the
way immunosuppressants are used. He had brought together many of his
former patients, including some he had operated on in the early
1960s. He learned that some of them had stopped taking their drugs
long ago and were doing just fine. Starzl tested these patients,
hoping to see something consistent; he observed donor cells in
various tissues and blood.

THOMAS E. STARZL:
Advocates immune tolerance as a transplant strategy. One method:
infusing cells from organ donors into recipients weeks before
surgery. Immunosuppressive drugs have boosted survival rates, but
they also increase the risk of infections, cancer, hypertension and
other illnesses. "He is a visionary, a tremendously large figure.
You need people like that in emerging fields." —Nicholas L. Tilney,
Harvard Medical School.

32 SCIENTIFIC AMERICAN
FEBRUARY 2007