ONE of the first things Lynda McKenzie, a 46-year-old Canadian artist and
writer with Parkinson鈥檚 disease, recalls about the operation she had 30 months
ago is the dull whirring of a drill as it cut four holes through her
anaesthetised forehead. 鈥淚t鈥檚 like being at the dentist,鈥� she says. 鈥淵ou hear
the drill, but you don鈥檛 feel it.鈥�
Later, through the haze of sedation, she heard the surgeon ask for the
鈥渋mplants鈥濃�攁 reference to the fetal cells that are injected deep into the
brains of Parkinson鈥檚 patients in an effort to compensate for neurons destroyed
by the disease. After the operation, McKenzie says she felt her Parkinson鈥檚 had
definitely improved.
But McKenzie did not receive any implants. She was part of a control group of
patients who had the operation, but not the injection. 鈥淚 was told that might
happen,鈥� she says. 鈥淏ut I was sure that I had received the tissue.鈥� Her symptoms
were temporarily soothed just by the act of healing鈥攖he placebo
effect.
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Placebo surgery鈥攁 practice that many doctors thought had been abandoned
forty years ago鈥攊s making a comeback. It is an integral part of two other
clinical trials for Parkinson鈥檚 treatment currently under way, a recent trial of
chronic pain treatment in cancer patients and another for knee surgery.
Advocates say placebo surgery allows the same scientific rigour accepted in the
rest of medicine to be applied to surgical techniques. But critics question the
wisdom鈥攁nd the ethics鈥攐f operating on patients without trying to
cure them.
Placebos are best known for their role in drug trials. One set of patients is
given the drug, the other set is given an inert substitute. Neither doctors nor
patients know who gets what, which stops them prejudging and biasing the
results.
By contrast, the principles behind surgery seem obvious. If something is
diseased, you cut it out or try to replace it. If something falls off or breaks,
you sew it back on or mend it. So surgical techniques are often adopted before
they have undergone clinical tests.
But testing surgery with placebos is not a new idea. It was used in the 1950s
to test a treatment for angina, in which two arteries in the chest were tied off
to direct more blood to the heart. Although three-quarters of patients
showed a marked improvement after the procedure, many surgeons were sceptical.
Their suspicions were confirmed after a small study by a Seattle doctor, Leonard
Cobb, and his colleagues in 1959. Half his patients had the operation, but in
the other half, the surgeon cut into the chest but didn鈥檛 tie off the arteries.
To the shock of proponents of the procedure, both groups showed equal
improvement (New England Journal of Medicine, vol 260, p 1115). The
operation was soon abandoned.
Back to the old ways
Despite this success, the future of placebo surgery didn鈥檛 seem bright.
Surgeons soon returned to their traditional ways. And in the 1970s, ethicists
began to worry that patients in clinical trials should be thoroughly informed of
any dangers before giving consent. Without much discussion, it was assumed that
no patient would agree to fake surgery once they knew of the risks.
The reason for the recent revival of sham surgery in the US is unclear. Some
experts suspect it is partly driven by insurance companies which want stricter
proof that techniques work before they pay for them.
Curt Freed of the University of Colorado Health Sciences Center in Denver,
one of the leaders of McKenzie鈥檚 trial, says he turned to placebo surgery after
reaching an impasse in his research. Along with his colleague, Robert Breeze,
Freed had been experimenting with fetal neuron transplants in Parkinson鈥檚 since
1988.
After years of study, they had developed what appeared to be a successful
approach. 鈥淎ll our patients were saying positive things about the therapy,鈥� he
says. But drug trials with Parkinson鈥檚 patients had shown that they are highly
susceptible to prolonged placebo effects.
Because of this uncertainty, Freed and his team convinced the US National
Institutes of Health to fund a placebo-controlled trial of their procedure on 40
patients.
The challenge, says Freed, was to design a study that balanced the safety of
the patient against a convincing sham. They decided to drill holes in the
placebo patients鈥� heads, but only to touch the protective surface of the brain
without penetrating it. Both real and fake operations followed a set script,
including鈥攁s McKenzie correctly recalled鈥攁sking for the implants
even if they weren鈥檛 to be used. Only Freed and the surgeon knew who received
the fetal tissue and who did not. The doctors who evaluated the patients over
the next year weren鈥檛 told.
The results of the trial were announced in April at the meeting of the
American Academy of Neurology in Toronto, Canada. The researchers found a strong
placebo effect鈥攁ll the patients reported an improvement. However, the
study also found that the implants had grown in nearly all patients who received
them. And implant patients under 60 years of age showed a 30 per cent
improvement in motor skills, compared with those who had the placebo
operation鈥攁lthough older patients showed no improvement. The complex
results proved to neurosurgeon Michael Walker, former director of the NIH
division that funded Freed鈥檚 work, the crucial role that placebo surgery played.
鈥淲ithout that comparison, we鈥檇 be arguing into the next millennium whether the
surgery had an effect or not,鈥� he says.
But others worry that the research might be sacrificing patients鈥� rights in
the hunt for scientific rigour. 鈥淒rilling into someone鈥檚 head is pretty
radical,鈥� says Bill O鈥橬eill, ethics and science adviser to the British Medical
Association in London. 鈥淚鈥檇 be very surprised for a hospital ethics committee in
Britain to approve such a placebo.鈥�
William Andereck, chairman of medical ethics at California Pacific Medical
Center in San Francisco, says the term placebo surgery is misleading because
placebos are innocuous, while surgery always carries a risk. 鈥淚t鈥檚 one thing to
give patients a sugar pill,鈥� he says. 鈥淏ut it鈥檚 not acceptable to give them
strychnine instead.鈥�
But if sham surgery has its critics, it also boasts some converts, among them
Thomas Freeman of the University of South Florida, Tampa. Initially, a
Parkinson鈥檚 trial led by Freeman was not going to include a placebo surgery
control. 鈥淚 dismissed it on a reflex basis, as most surgeons would,鈥� he says.
But in the end, he decided it was better to expose a few placebo subjects to
some risk than end up promoting a potentially dangerous operation to hundreds of
future patients.
But no one is quite sure where to draw the line. Donald Kornfeld sat on the
hospital ethics board at Columbia Presbyterian Center in New York city that
eventually approved Freed鈥檚 trial. They decided that the benefits and risks of
the placebo and experimental groups were well balanced. And after the trial,
placebo patients were given the choice of receiving implants, so treatment was
only delayed.
But Kornfeld鈥檚 committee turned down a similar trial to inject nerve cells
from pigs into Parkinson鈥檚 patients. They decided that the protocol, which
called for months of treatment with antibiotics in both groups, was asking too
much of control patients. Other centres, however, agreed to participate and the
trial is in progress.
McKenzie, who has now had the real surgery, feels she was thoroughly
informed. 鈥淚t鈥檚 wrong for anyone to say I was a sacrificial lamb,鈥� she says.
鈥淲e鈥檙e on the last crunch in making advances on this disease. Being in this
study is a part I can play.鈥�