Hard graft wins Nobel for working doctors

13 October 1990

TWO DOCTORS who loved the clinic more than the laboratory have won this
year’s Nobel Prize for medicine. Joseph Murray, a surgeon from Boston, was
the first to succeed in transplanting a kidney from one identical twin to
another. E. Donnall Thomas, a Texan now living in Seattle, pioneered the
technique of bone marrow transplants.

One leading researcher called Thomas ‘an outstanding clinician who stands
head and shoulders’ above all others in his field. And the success of Murray’s
‘extremely bold’ surgery opened the way for transplants of other organs
such as the liver and heart. Thomas said he never dreamed he would win a
Nobel Prize because he worked with patients rather than on basic research.
‘I thought it was such a long shot that I wasn’t even in the race. The most
exciting thing is the general acceptance of bone marrow transplantation.’

Thomas’s centre at the University of Washington has become a Mecca for
physicians, according to George Santos, professor of oncology at Johns Hopkins
University. There, during the 1970s, Thomas achieved the first successes
in treating leukaemias and other blood diseases such as thalassaemia by
transfusing patients with bone marrow taken from a related donor. When the
transplants were successful, the new cells from the donors enabled these
patients to manufacture their own blood cells and cells of the immune system.

Thomas’s early research in dogs and other animals demonstrated the importance
of matching the tissue type of the donor and the recipient as closely as
possible. The same principle applies in humans .


When an organ is transplanted into a host, the host’s immune system
attacks the foreign antigens it recognises in the transplanted tissue. To
prevent the graft from being rejected, doctors treat the patient with drugs
that suppress the immune response. When bone marrow is transplanted, not
only does the host attack it but cells of the donor’s immune system present
in the marrow go on the offensive against the host’s tissue, creating a
reaction known as ‘graft versus host’. The work in Seattle showed that it
was possible to prevent the graft-versus-host reaction by treating the patient
with a cell-killing drug called methotrexate.

Thomas conducted clinical trials of bone marrow transplants between
relatives on a scale unknown elsewhere. Santos at Johns Hopkins believes
that Seattle may have treated as many as half the patients in the world
receiving bone marrow transplants.

The Texan is a quiet and reserved man of 70 who enjoys going fishing.
Murray, too, is a man of few words. ‘I suspect he was a much more prominent
figure than was realised because he didn’t go round talking about it all
the time,’ said Peter Morris, Nuffield Professor of Surgery at the University
of Oxford. The surgeon was the first to succeed in implanting a donated
kidney into the pelvis of the recipient and attaching it, via the ureter,
directly to the bladder. The technique, first used in December 1954, is
still in use today.

Richard Herrick, the patient in that first transplant, received a kidney
from his identical twin Ronald at what was then the Peter Bent Brigham Hospital
in Boston. Herrick lived for eight years. Previous attempts at kidney transplantation,
which began as early as the 1930s in the Soviet Union, had failed. No one
before Murray had tried to implant the kidney in the pelvis; others had
attempted to insert the organ into the groin and even under the arm.

Thomas was also at the hospital – now the Brigham and Women’s – at the
time of the initial success. Both Thomas and Murray are graduates of Harvard
Medical School. Murray went on to transplant kidneys between non-identical

In a transplant between identical twins, there is less risk of the organ
being rejected because the cell-surface antigens are largely the same. The
challenge comes when the donor is less closely related. In this type of
transplant, the recipient’s immune system has to be suppressed by killing
the T cells of the immune system. Murray initially did this by irradiating
the whole body of the patient with a high dose of X-rays. Later, with a
young British researcher, he went on to find a less hazardous form of treatment.

That researcher, now Sir Roy Calne, is now at the University of Cambridge.
When he went to Boston, he had just discovered that azathioprine could prevent
the rejection of tissue in animals. When Murray saw Calne’s results for
azathioprine in animals, he conducted trials of the drug in people and these
were highly successful. From the mid-1960s until 1980, azathioprine was
given to all patients receiving a transplant. Since that time Calne’s group
in Cambridge has discovered a less toxic drug called cyclosporin.

The Nobel Assembly’s citation says that ‘Murray discovered how rejection
following organ transplantation could be mastered’. Murray’s undoubted success
was as a surgeon and a clinician, but the credit for discovery of a drug
for immune suppression must go to Calne. The statement in the citation is
‘extraordinary’ says Calne, but he said he would phone Murray and congratulate
him immediately.

While Murray was pioneering transplant techniques in Boston, doctors
such as Jean Hamburger and others in Paris were working on the same treatment.
It is difficult, according to some researchers, to single out the greatest
in the field. ‘The French will be mad. I personally thought they would never
give a Nobel prize for transplantation,’ says Morris, because more than
three workers deserve it.

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