Authors: Richard Hollingham
Medicine was no stranger to the wonders of the atom. X-rays
had revolutionized diagnosis and allowed surgeons to see moving
images of the inside of the body (see Chapter 2). Radiation was also
being used to treat cancer, helping to save many thousands of lives
a year. Other doctors were studying the biological effects of radiation
– vital to refine treatments, ensure people's safety and, of
course, plan for the aftermath of a Third World War.
Ever since the first atomic bombs were dropped on Japan in
1945, scientists had been building up a better understanding of the
effects of radiation on the human body. Doctors had been able to
examine victims of radiation sickness as their symptoms progressed
from vomiting, diarrhoea and fatigue to the full-blown and invariably
terminal signs – hair loss, uncontrolled bleeding and heart failure.
They found that some parts of the body were affected more
than others, and when scientists started to look at individual cells
(often during post-mortems) they concluded that some cells were
more sensitive to radiation than others. The most vulnerable cells
turned out to be those that line the intestine (hence the vomiting
and diarrhoea) and also the cells of the immune system – the white
blood cells. Enough radiation and the immune system could be
completely wiped out. This discovery got the transplant surgeons
thinking. Could radiation be used to overcome the body's defences
and break down the barrier to successful organ transplants?
A few experiments were tried on animals with varying degrees
of success, but despite some misgivings, the surgeons at Peter Bent
Brigham Hospital in Boston decided to go ahead and treat their
transplant patients with radiation. Joseph Murray planned to use Xrays
to suppress his patients' immune system before conducting a
transplant. This would, in theory, avoid rejection and allow the
transplant to 'take'. Their patients had nothing to lose – they were
going to die anyway – so any new idea was worth a try.
The first patient was thirty-one-year-old Gladys Loman. A
mother of two, she had been born with only one kidney. When it
became infected it was accidentally removed in an emergency
operation. The surgeon responsible thought he was removing a
diseased appendix. This left Loman with no kidney at all and only
weeks to live. She was referred to Joseph Murray, who gave her
dialysis to keep her alive. This, he warned her, could be used only a
few times. After that she would either die or he could attempt his
experimental new procedure.
Gladys Loman lay on a mattress beneath the X-ray machine. She
was curled up in a foetal position to expose her immune system to
the radiation. The X-rays would destroy the white cells in her spleen,
lymph nodes and bone marrow. Radiation would wipe out her
body's defences and leave her completely vulnerable to the slightest
infection. The surgeons turned on the machine and left the room
for their own safety. Gladys lay on the mattress for three hours trying
not to move. Above her the X-ray tubes bombarded her with massive
amounts of radiation.
Following the procedure he had adopted with Richard and
Ronald Herrick, Murray transplanted a healthy kidney into Gladys.
The kidney had been taken from a stranger and would normally
have been used by researchers at the hospital who were studying
polio. Gladys's new kidney was completely alien to her body. The
question was, now that her immune system had been destroyed,
would she accept the new organ?
To avoid the risk of infection, Gladys was housed in a completely
clean room – actually a converted operating theatre. When anyone
came to see her they had to scrub their hands and wear operating
gowns, hats, masks and gloves. She couldn't leave – she was trapped
in this sterile hospital prison.
At first the new kidney failed to work, but eventually, after two
weeks, it started to produce urine. It looked like the operation had
been a success, so the surgeons gave Gladys a bone marrow transplant
to try to give her immune system a boost. But her body had had
enough. Thirty days after the transplant operation she was dead.
Gladys had endured dialysis, major surgery and massive doses of
radiation. She had coped with pain and discomfort, and spent a
month isolated from the world in an operating theatre. All that for
a few extra days of life. You have to wonder whether it was worth it.
Staff at the hospital were becoming more and more despondent,
and one surgeon quit altogether. Despite his own misgivings, Murray
still believed the immune system could be overcome, and pressed on
with the total irradiation procedure for eleven more patients.
By the third patient, twenty-six-year-old John Riteris, the surgical
team had refined the procedure. Instead of administering the
radiation in a single large dose, they used the X-ray treatments in
shorter bursts. They studied cases of people involved in nuclear
accidents and looked again at data from animal experiments. With
Riteris, it helped that the kidney donor was the patient's brother;
they were twins, but not identical twins. Their differences were
revealed when a skin graft between them was rejected.
Nevertheless, the surgeons reckoned that they still might have a
better chance of success.
Riteris's new kidney worked almost immediately. Although his
white blood cell count was alarmingly low, he managed to remain free
of infection. Better still, it looked like the organ wasn't being rejected.
Over the next few months he was given further doses of radiation, as
well as anti-inflammatory drugs. Eventually, he left hospital with a
working kidney and went on to lead a normal, healthy life. At last the
surgeons had broken another barrier – they had shown it was possible
to transplant organs between non-identical brothers.
But any triumph was short-lived. All the remaining transplant
patients who received total body irradiation treatments at the hospital
died. Radiation suppressed the immune system, but in doing so
it laid the patients wide open to infection. It was the infection that
killed them. The atomic dream was over. Surgeons needed to look
for something else.
Cambridge, England, 1976
The odds on surviving a transplant operation were improving every
year, but they still weren't great. By 1965 around four out of five
transplant operations were successful if the donor and recipient
were related. If they weren't related, the odds fell to around one in
two. In the UK in the early 1960s one of the world's most experienced
transplant surgeons had conducted a series of fourteen
kidney transplant operations. Only one patient survived.
There had, however, been a number of innovations during the
1960s that made transplants more likely to succeed. Surgeons were
now able to match the immune systems of the donor and recipient
more closely. This process, known as tissue typing, greatly improved
the odds on the transplanted organ being accepted. And, with total
body irradiation abandoned, scientists had developed new drugs to
help combat the immune system's defences. Still, going into hospital
for a transplant operation could be a grim experience, especially for
children. A nine-year-old girl admitted to the Royal Infirmary in
Edinburgh in 1967 later described how she was kept in isolation to
avoid the risk of infection. For the five weeks following her kidney
transplant operation, the only people she came into contact with were
masked nurses and doctors, who had to scrub and shower before
entering and leaving her room. The girl's parents were barred from
entering, and could only communicate with her through a window.
*
*
Fortunately, the discomfort was worth it. The girl's kidney was still working more than
thirty years later.
As for the new drugs, they came with a substantial health warning
and a list of side effects that ran to a small dictionary. They
might suppress the immune system, but the A–Z of nasty things
these drugs could also do to the body ranged from the inconvenient
to the fatal: from alopecia to tremor, anaemia to ulcers, cancer
(through heart disease and nausea) to osteoporosis. A common side
effect of, for instance, the steroids being prescribed, was facial
swelling – a syndrome known as 'moon face'.
Even with the drugs and the tough procedures to keep patients
isolated from infection, too many transplant patients were dying.
But this didn't stop surgeons trying new and daring operations. By
1970 they had moved on from transplanting kidneys to livers and
the pancreas. They had even transplanted a human heart (see
Chapter 2). But organ transplants were increasingly perceived as the
last desperate measure of an increasingly desperate branch of
surgery. Many hospitals refused to carry out transplants – it hardly
helped their mortality figures. Murray later described the period at
the end of the 1960s as 'transplantation's darkest hour'.
Then surgeons had a stroke of luck. Jean Borel, a young
researcher at the Swiss drug company Sandoz, was given the task of
examining a bag of Norwegian soil. The soil had been gathered
during an expedition to a bleak highland plateau, and it was Borel's
job to see if he could find anything useful in it. After careful analysis
he was rewarded with the discovery of a new type of fungus from
which he extracted a chemical. They called it cyclosporine A. This
was no new penicillin – cyclosporine A was useless at killing bacteria
– but it did appear to have a dramatic effect on the immune system.
Borel found that cyclosporine suppressed the function of the T cells
(specifically the helper T cells), preventing the immune system
from attacking alien tissue.
In 1976 Borel attended an English surgical conference to report
his findings. When the transplant surgeon Roy Calne heard about
the remarkable new substance Borel had discovered, he couldn't
wait to get his hands on it. Calne had been one of the pioneers of
transplant surgery, and among the first to use drugs to suppress the
immune system. He had teamed up with Murray in the 1960s and
had been instrumental in improving the success of organ transplants.
Now Calne wanted the opportunity to try cyclosporine.
Could this drug finally provide the breakthrough surgeons so
desperately needed?
Calne persuaded Sandoz to send him a sample of cyclosporine
so that he could try some experiments for himself. But when the
sample turned up there was a major snag: it was in its purest form –
as a white powder – and the researchers in Calne's Cambridge
laboratory couldn't get it to dissolve. Neither water nor any of the
other common solvents they had lying around the lab worked. This
meant that if cyclosporine was made into a pill, it wouldn't be
absorbed in the gut. As a drug, it was all but useless. Sprinkling some
white powder on the transplanted tissue to see what happened
wasn't really an option. In the end the future of transplantation
surgery was saved by a protective mother. Alkis Kostakis's mother
to be precise.
Kostakis was a visiting research fellow from Greece, but his
mother was worried. She was particularly worried about English
food, and with good reason. In 1976 English cuisine was, as a rule,
lurid, processed and bland. Even the blandest of English foods, the
potato, now came in freeze-dried granules; green vegetables were
boiled to slime; and Angel Delight – a mousse-like substance with an
indeterminate flavour – was considered a sophisticated dessert.
Orange juice (in bottles) was a once-a-week treat and bread (white,
sliced) had all the nutrients baked out of it as a matter of course. No
wonder Mrs Kostakis was worried.
She sent her son a bottle of finest Greek extra virgin olive oil. But
before Alkis could drip it on to his salad (iceberg lettuce was probably
the best he could hope for), he took the oil into the lab. More
in hope than expectation, he decided to try mixing it with the
cyclosporine. He had nothing to lose, so he carefully measured out
the oil and ladled it over the precious fungus powder. The drug
dissolved. He tried out his combination of olive oil and cyclosporine
on a series of animal patients. The results were spectacular. They
were so spectacular that Calne didn't believe him, so he sent Kostakis
back to repeat them. But he got the same results again – cyclosporine
mixed with olive oil worked wonders. Soon Calne could start trials in
human patients; he would transform the world of transplant surgery.
All he had to do was lay his hands on more cyclosporine.
But Sandoz, the company that had discovered cyclosporine, was
not convinced. The way things had been going with transplant
surgery in recent years, they saw no future in cyclosporine. As far as
they were concerned, it would only lose them money. Calne flew out
to see them. He talked to their financial people, he argued, he
cajoled, he badgered. He told them this was the best thing he had
seen in all his years of transplantation. Finally, Sandoz gave in and
agreed to conduct a limited drugs trial. They were still reluctant. It
would, they warned, almost certainly lose them money.
Surgeons began testing the drug on transplant patients in 1978.
With the introduction of cyclosporine, survival rates rocketed. One
year after their liver transplant operations some 70 per cent of
patients were alive, and almost 80 per cent after kidney transplants.
Cyclosporine wasn't without its own side effects, and the risk of
infection was still a major problem, but it looked like the immune
system had finally been overcome.
In 1990 Joseph Murray was awarded a Nobel prize for his work
on organ and cell transplantation (he shared the award with E.
Donnall Thomas, who had developed drugs to minimize rejection).
Roy Calne was knighted for his transplant research in 1986 and is
one of the few surgeons to be elected a fellow of the Royal Society.
In the bloodstained history of surgery, transplants stand out as
an area where even the best surgeons have been defeated time and
time again. From Spence's disastrous tooth transplants to Carrel's
sinister laboratories, experiments with decapitated French criminals
and total body irradiation, transplantation surgery is littered with illconceived
ideas, gruesome experiments and procedures bordering
on the unethical. It took until the mid-1980s for transplant surgery
to become a safe, routine surgical treatment. After more than two
hundred years the battle with the body's own defences had been
won. Now anything was possible. Hearts, livers, lungs, kidneys;
surgeons could even transplant a dead man's hand.