When Science Goes Wrong (3 page)

The central biological process that causes the symptoms of Parkinson’s disease is thought to be the death of a set of brain cells that produce a neurotransmitter, or signalling molecule, called dopamine. These cells are located in a small region of the brainstem called the
substantia nigra
or ‘black substance’ – so-called because these cells are heavily pigmented. The cells have extensions called axons that run from the
substantia nigra
to the striatum, a structure higher up in the brain that helps to generate body movements. (More accurately, there are two striatums, one in the left and one in the right hemisphere of the brain.) The tips of the axons – the synapses – release dopamine into the striatum, and this release is vital for normal function.

In Parkinson’s disease, the cells of the
substantia nigra
gradually die over a period of years or decades, and their axons die too, so the striatum is gradually starved of its supply of dopamine. Well over half of the dopamine cells have to die before the disease shows itself, however: thus, a person who experiences symptoms for the first time has actually harboured the underlying disease process for years without knowing it.

Of course, people who develop Parkinson’s disease want to know why
they
got the disease rather than someone else. In most cases, the answer isn’t known. Doctors commonly describe the disorder as ‘idiopathic’, meaning that it seems to develop of its own accord without any obvious external cause. Still, there are some clues. In particular, chronic exposure to pesticides, herbicides, and other environmental pollutants raises the likelihood of developing the disease. What’s more, some people have a genetic makeup that makes it hard for the body to break these pollutants down, and this makes such people more likely to develop Parkinson’s disease if they are chronically exposed to pollutants.

Truex might have been exposed to agricultural pollutants during his childhood, when he lived in a farming area, drank well water and ate fish caught by his father in a polluted lake. Also, as mentioned earlier, Truex was exposed to a variety of toxic agents in his adult life as a result of training and racing in highly polluted air. Still, it will never be known for sure whether these exposures were a factor in his developing Parkinson’s disease, or whether his case was truly ‘idiopathic.’

The mainstay of treatment for Parkinson’s disease is the drug L-dopa. Once ingested, this drug enters the brain, where it is transformed into dopamine and thus makes up for the brain’s own deficient supply. It is usually taken in a proprietary form called Sinemet, in which the L-dopa is combined with another drug that protects the body from some of L-dopa’s potentially harmful side-effects. Truex did take Sinemet, and it helped him, but it did not prevent the progression of his disease. In particular, his speech began to be affected. He spoke too rapidly: when he was speaking in court, the court reporter would ask him to slow down, but somehow he couldn’t. Then his voice weakened, so that it was hard to hear him in any kind of noisy environment, and he also began to slur his words. Max’s brother Don told me that he took Max to task for ‘mumbling’ – he didn’t realise that it was a symptom of his disease. ‘I said, “Max, you earn your living talking, you’ve got to talk so that you can be heard.”’

In spite of these problems, family life went on in a reasonably normal fashion. About six months after Max was diagnosed, their daughter, Mindy, was born. Max did as much as he could to help with the children. And he even kept on running. He now knew that his disease was likely to progress, but he focused on the hope of remaining an effective father and provider for as long as the children needed him.

Unfortunately, within two years or so, his voice deteriorated to the point that he could no longer function effectively in court. Truex wanted to continue working by concentrating on office work, but the county thought otherwise: they retired him on a disability pension. The pension was adequate to maintain the family’s standard of living, but the sudden termination of his career was a brutal experience for an active man like Truex. He worked for a few months in the office of a colleague, then quit working entirely.

Gradually, the disease started to close in on him. He began to have problems driving, especially when he needed to make rapid turns of the steering wheel. He had always looked forward to being an active role model to his children, taking them backpacking and skiing, teaching them athletics and so on, but all these things became harder and harder. His doctor frequently increased the dosage of his drugs or added new ones, but they never quite kept up with the advancing disease. Max’s walking became stiff and slow, and getting up from a chair required a great effort. He had to give up running – a terrible blow.

The Truexes thought that living in Los Angeles might be too demanding for Max, and they decided to move somewhere with a slower pace of life where he might be able to continue with activities such as driving. At the urging of an old Air Force team-mate who lived in Gunnison, Colorado, they moved to that city. Both Max and Kay liked Gunnison. (‘It was like being on vacation,’ says Kay.) But the move did nothing to slow the advance of Max’s disease. He began to experience episodes of ‘freezing’, when he simply got stuck in the middle of what he was doing and couldn’t move at all. His walking became unsteady to the point that he was in constant danger of falling. The tremor in his arms worsened. And after he got into two car accidents in the space of two days, he had to give up driving for good.

Max remained under the care of his doctor in California, who juggled Max’s drugs as best he could. He was taking about 30 tablets a day, some of them intended to treat the disease, and some to counteract those drugs’ side-effects. As often happens with people with Parkinson’s disease, it became unclear which of his drugs were helping him and which were harming him, and so his doctor decided to take him off all his drugs for a couple of weeks so that he could be ‘re-levelled’. The idea was to reintroduce the drugs one by one, while observing what effects they had. During the time that Max went without the drugs he stayed with Don in Santa Barbara, so Don got to see the full extent of Max’s disease in its untreated state. ‘He came unglued,’ Don told me. ‘He couldn’t do anything. He couldn’t even swallow.’

The re-levelling may have led to some temporary improvement, but Max soon began to go downhill again. By the mid-1980s, he was having trouble with dressing, cutting up his food, and any other task that required delicate control of movement. His symptoms seemed to change from day to day. ‘If I was paralysed from the waist down,’ Kay remembers him saying, ‘I would know what I could do and what I couldn’t do, but with this I never know whether it’s going to affect my ability to walk, my ability to speak, whether I’m going to shake or not shake, I never know which part of my body is going to go.’

Max struggled on. As his sons got to the same age as he was when he started running, so did they. Max tried to coach them, but often Kay had to help out. Max’s friends from his college and Air Force days rallied round. Kay recounts how one friend insisted on taking Max and his family to Vail for a skiing vacation: ‘He said, “I don’t care how many times you fall, Max, I’ll pick you up.” And he did.’

Toward the end of the 1980s, when Max had been battling Parkinson’s disease for nearly a decade, things began to get rapidly worse. As so often happens with L-dopa treatment, the drug had begun to lose some of its effectiveness, and even with the addition of other drugs he was in a serious plight. Now Kay had not only to cut up his food but to lift it to his mouth, too. And his swallowing was impaired almost as severely as when he had been off the drugs entirely: he would choke on his food as often as he swallowed it. Max became quite depressed and anxious about his future.

One person who followed this decline with great concern was his old track coach, Jim Slosson. When Slosson met Max in 1988, he was devastated to see how this brilliant athlete had been reduced to a shuffling invalid. A little later, Slosson was having dinner with one of his own old track buddies, a half-miler by the name of Paul Iacono, and he told Iacono about Max’s illness. As it happened, Paul had a son, Robert, who was a 36-year-old neurosurgeon with a special interest in Parkinson’s disease, so Paul arranged for Max to meet him.

I visited Dr Iacono in the year 2000 at his office in Redlands, California. He was a handsome and still young-looking man with black hair and a full, black moustache. He certainly looked to be of Italian descent, as his name suggested. What was most memorable about him, though, was not his appearance but his manner of speech. He was unstoppable, and often very colourful in his choice of words. He seemed perpetually on the brink of saying more than would be wise. An interview that I expected to last for less than an hour went on for three hours, during which time I barely had the opportunity to get in a few questions. Various assistants and medical students drifted in or drifted out during our meeting, as if to get samples of their boss’s oratory.

Back in 1988, Iacono was based at the University of Arizona Health Sciences Center and the Veterans Administration Hospital, both located in Tucson. He had gone to college and medical school at USC, and he had done further training at Duke University where he had developed a special interest in the underlying mechanism of Parkinson’s disease. ‘I was mostly grinding on new theory,’ he told me. ‘I wrote a couple of hundred papers when I was at the University of Arizona on neurobiological theory because I was trying to pave a new trail into the unmarked stuff. Because the marked stuff, the dogma, is just crap when it comes to Parkinson’s disease.’

If Iacono did write that number of papers, most of them must have remained unpublished or else they were published in minor periodicals that are overlooked by the indexing services. But those that are available do attest to his iconoclastic approach to neurology during that period: they suggested novel causes and novel treatments for a number of disorders. In a paper published in 1990, for example, he suggested that a cluster of brain cells named the
locus coeruleus
played an important role in the development of Parkinson’s disease. The neurotransmitter used by those cells is not dopamine but a related compound named norepinephrine (also called noradrenaline – it’s a close chemical relative of adrenaline). If true, Iacono’s hypothesis would suggest treatment options quite different from the traditional dopamine-related drugs used for the disease, such as L-dopa.

Thus, Max Truex was coming to visit a doctor with a very different mindset from the conservative neurologists who provided his regular care. Furthermore, Iacono was not a neurologist at all, but a neurosurgeon. By that token, he might be expected to think in terms of dramatic one-time solutions, rather than the painstaking manipulation of drug dosages over months or years.

Truex’s visit was also different in the way he was treated. Whether because he had been referred by Iacono’s father, because both men had been at USC, or because Truex, like Iacono’s father, had been an outstanding runner, Iacono treated him much more as a family friend than as a patient. He picked Truex up at the airport, for example, and had him stay at his own home during his time in Tucson.

Although Iacono may have been a radical thinker, he said that it was Truex, not himself, who pushed for radical treatment. ‘I said, “You look well-medicated, I don’t know what I can do for you,” but he said, “No, Bob, I need something.”’

Nothing was decided on during that visit, but Truex continued to call Iacono at his home on a more or less weekly basis for about a year. During this period, the Truexes moved to Boston so that Kay could enter graduate school at Brandeis University – she was hoping to restart her academic career and thus bring some more money into the family.

Truex himself seemed to be researching his treatment options during this period, because on one occasion he said to Iacono, ‘What about this adrenal graft?’ This was a procedure popularised by doctors in Mexico, who took fragments from the patient’s adrenal gland and transplanted them into the brain, near the striatum. Adrenal gland cells produce a certain amount of dopamine, as well as other chemicals, so the thought was that they might make up for the lack of dopamine in the striatum of people with Parkinson’s disease. It turned out that the method didn’t work – the transplanted cells may have survived for a while and maybe even provided some benefit during that time, but within a few months they died, and the patients were as bad off, or worse off, than they had been beforehand. Nevertheless, there was a short period of enthusiasm for the procedure right after the Mexicans published their findings in 1987, and Truex heard about it and proposed it to Iacono as a possible remedy for himself.

Iacono knew that the adrenal transplants were not working as well as advertised, so he talked Truex out of that particular option. But Truex still wanted something done. He kept calling and visiting Iacono. After a few months of this pressure, Iacono felt that he had to do something. So he decided that Truex should undergo a procedure that was even more radical than an adrenal transplant – a transplant of cells from the brains of human foetuses.

Foetal tissue transplantation as a possible treatment for Parkinson’s disease had been pioneered by researchers in Sweden, led by Anders Bjorklund. In the late 1970s, the researchers had created an animal model of Parkinson’s disease: they treated rats with drugs that destroyed their dopamine cells, which left the animals with a movement disorder that was somewhat analogous to Parkinson’s disease. Then they took tissue from the
substantia nigra
of foetal rats – tissue that contained immature dopamine cells – and transplanted it right into the striatum of the treated animals. After a few weeks, the animals’ ability to move improved greatly; sometimes they seemed close to normal in their behaviour. The transplanted dopamine cells had survived and matured in their new home, and they were supplying at least some of the dopamine that the rats were missing.