LONDON, 7 July 2004 — Last week’s announcement that a team of Israeli scientists had successfully used human embryo stem cells to treat rats with symptoms of Parkinson’s disease raised hopes that a similar effect might be possible in humans. For those afflicted by this miserably debilitating condition, it is light at the end of a dark tunnel. But for those unaffected, having cells injected into your brain sounds like extreme medicine: a Frankenstein treatment.
Yet my guess is that Dr. Benjamin Reubinoff, who led the study at Hadassah University, already has a sackful of letters from people offering to be the first human guinea pigs — and this notwithstanding the distressing history of brain injections of fetal cells, which were touted as a treatment for Parkinson’s in the 80s and 90s. Despite initial results, which seemed promising, particularly in younger people, the bad news was that after a year some developed exaggerated symptoms known as disabling dyskinesias, which were permanent and irreversible.
Being worse off after last-ditch, last-hope treatments, seems very cruel. Yet they are never sold with guarantees; indeed, most come with dire warnings. The fact that people are still prepared to sign up for them is testament to the quality of life of those with chronic illness or pain; that and their desperate quest for hope.
Extreme medicine is usually reserved for those with immediately life-threatening illnesses. Robert Tools is typical. A retired telephone company employee, the 59-year-old American had been turned down for the heart-transplant program, had suffered multiple heart attacks, and also had diabetes and kidney disease. His life was ebbing away when in 2001 he received the world’s first self-contained artificial heart at Jewish Hospital in Louisville, Kentucky.
The AbioCor heart is the size of a grapefruit. It requires an external battery pack, worn on a belt, plus two extra bits of kit installed inside the body, an internal controller unit and a rechargeable battery (imagine someone telling you that they would like to insert a phone charger into your stomach). Tools lived for 151 days before succumbing to hemorrhage. “Mr. Tools and his family are heroes,” said his surgeon, Dr. Robert Dowling. “Their willingness to be the first to participate in the AbioCor clinical trial could potentially pave the way for a revolutionary treatment for heart disease.”
Seven-hour surgery in which someone cuts out your admittedly failing heart and replaces it with a machine untried in humans certainly qualifies as extreme medicine. And, as with treatments for Parkinson’s, previous history was not encouraging. In 1982, Barney Clark, a dentist from Seattle, lived for 112 days following the implant of Jarvik-7, the first device designed to be a completely permanent replacement heart. This air-driven device was an even more worrisome prospect. It was connected by protruding wires to a large external unit and it was these wires that did for Clark, introducing infection after infection into his body. Although four more patients received the Jarvik-7, its days were numbered. Enhanced and renamed as the CardioWest heart, its purpose today is solely as a bridge to transplantation.
Even these heroic operations were less extreme than those that preceded them in the quest to do away with reliance on scarce human organs. In 1963, a patient lived for nine months following the transplant of a chimpanzee kidney, and in 1984, a newborn baby, known as Baby Fay, survived 20 days with a baboon heart. In neither case was life significantly prolonged or quality of life improved. Yet researchers remain undeterred and we are still talking about the possibility of xenotransplants today, but with the organs being supplied from genetically engineered pigs. For those not lingering on a transplant list, xenotransplantation is an ethical nightmare, with many concerns, including the prospect of new disease caused by transplanted pig retroviruses. But the people waiting — and I have spoken to many — are prepared to live with the risks.
As transplant pioneer, Christian Barnard, put it: “If a lion chases you to a river filled with crocodiles, you will leap into the water convinced you have a chance to swim to the other side. But you would never accept such odds if there were no lion.”
Louis Washkansky, a 53-year-old South African grocer, found himself pursued by that lion. He became the recipient of the world’s first human-to-human heart transplant in 1967, surviving for 18 days. He is a legend and today — thanks to him and those that followed — heart-transplant surgery is successful and commonplace.
A heart transplant is an extreme solution to an extreme situation, but conditions that are not life threatening also prompt extreme solutions. Some years ago I made a film for the BBC about a man who had damaged the cornea of both eyes. Corneal transplants had failed and he was facing the prospect of being blind for the rest of his life. Somehow he was persuaded that taking out one of his teeth and putting a bit of it in his eye, would restore his sight. In an extraordinary operation, the tooth was removed (and yes, it was his eye tooth). It was cut down, providing a thin sliver of dentine, into which a hole was bored. The sliver was put into a pocket created in the man’s cheek. Three months later, it was removed and the frill of tissue that had by now grown around it was used to attach it to the man’s cornea. A week later I visited the man in a hospital in Brighton, where he was reading a newspaper.
Reconstructive surgery is also replete with extreme medicine, where toes are removed and fashioned into thumbs and bone is taken from the hip to be crushed into moulds to make new palates. But what all extreme medicine has in common is the patient’s absolute trust in his doctors. It doesn’t always have a happy outcome. The charismatic Irish surgeon, William Arbuthnott Lane (1856-1943), emboldened by the success of his treatment for constipation that involved removing huge sections of the gut, decided to do the same thing as a prophylactic measure for those who weren’t actually ill, but whom he considered at risk of “autointoxication”. It was detoxing at its most extreme and yet still his eviscerated patients adored him.
From the coffee enemas offered by Gerson Therapy to those with terminal cancer, to new surgical treatments such as islet transplants for diabetics, and even face transplants for burn victims, those with lifelong or life-threatening conditions willingly submit to treatments that are dangerous because they feel that they have nothing to lose. In these circumstances, where an untried treatment is the only hope, can proper consent ever be given and should those not afflicted make judgments about what people in desperate pain and suffering can or can’t do to their bodies? Should the patients be protected from themselves, and more to the point, from their doctors who may be exploiting their hope to extend their skills and knowledge?
The case of 18-year-old Jesse Gelsinger in 1999 changed thinking. Gelsinger had a rare genetic disease that affected the way ammonia, the toxic by-product of protein breakdown, was cleared from his body. He had a mild form of the disease that was controlled by drugs and diet and was not life-threatening, but nevertheless volunteered for gene therapy — then, and now, an extreme solution — at the University of Pennsylvania’s gene therapy unit. Four days later, he was dead, killed by a severe immune system reaction.
A subsequent inquiry revealed that neither Gelsinger nor his family had been told of similar reactions in animal trials, his liver test results should have made him ineligible for the study and poor results of other gene-therapy volunteers had not been made available to the regulatory body at the FDA. Disturbing details about the way that people — who would not themselves benefit from the trial — were recruited to it, and the intense commercial interest in its outcome, were uncovered. As a result, the FDA stopped many gene therapy trials and tightened regulations on consent.
Some ethicists believe that there is no such thing as informed consent in life and death situations and that some other third party should give consent. It’s a thorny subject that gets to the very heart of whose life it is anyway. What is certain, however, is that without pioneer patients such as Washkansky, extreme medicine cannot develop into common or garden everyday lifesaving. We have much to thank them for.
