When Science Goes Wrong

by Simon Levay

  The next question was where and how Truex was to get the transplant. Iacono first contacted the Swedish group, hoping that they would accept Truex as a patient. They turned him down, however, because they preferred Swedish patients who they could monitor for long periods after the transplant. Then Iacono found out that a group at Yale University was gearing up to perform similar transplants and was looking for volunteers. But, as it turned out, the Yale group also wanted people who lived locally. A group in England also turned Truex down. Iacono was stymied.

  Then, in November 1988, the first American foetal transplant was performed by a team led by neuroscientist Curt Freed of the University of Colorado. Freed had researched the technique for years, first in rats (like the Swedes) and then in monkeys. This research was funded by federal grants, but when he began the human work Freed had to turn to private funds because the Reagan administration, concerned about the abortion issue, had banned the use of federal grants to support transplantations involving human foetal tissue.

  For the first transplant, Freed selected a volunteer by the name of Don Nelson, a 51-year-old Denver man who had been suffering from Parkinson’s disease for 19 years. As with Max Truex, Nelson was deteriorating fast and he was desperate to try some new therapy. Freed obtained foetal tissue from an abortion clinic in the Denver area, dissected out the substantia nigra and (with the collaboration of a neurosurgeon) injected the foetal cells into the striatum on one side of Nelson’s brain.

  If the Swedes were publicity-shy almost to the point of secretiveness, Freed was the very opposite: he held a news conference to announce the transplant just two days after the operation, long before he could know whether Nelson would experience any benefit from the procedure. Part of the reason for his haste may have been that the Yale group was about to do their first transplant – it actually took place just a few weeks later. In the world of medical research, priority is a significant issue.

  Iacono did not contact Freed to see if he would accept Truex as a volunteer. Although I don’t know the exact reason, the fact is that Freed and Iacono didn’t get along. ‘I have no respect for Curt Freed,’ Iacono told me. ‘The results he’s got have been so poor that no one should be continuing that work.’ And he described some of Freed’s more recent experiments, in which he did mock surgery on some patients to establish a placebo control group, as ‘asinine and unethical.’ When I talked with Freed in 2000 – we were collaborating on a book about Parkinson’s disease – he was equally blunt about Iacono. He described Iacono as ‘one of the most, shall we say, provocative neurosurgeons who has not been censured by the academy of neurosurgery but whom everyone has said should be censured.’ Of course, this was after he learned about what happened to Max Truex; it’s possible that he was better disposed toward Iacono back in 1988.

  In any event, Iacono said that he made great efforts to find a place where Truex could get a foetal transplant. ‘I tried all my friends all over the world – Sweden, Britain, Japan. I tried and tried. And eventually, after two or three years of following Max, I realised I had to do it myself.’

  Do the transplant himself? Iacono was a neurosurgeon, certainly, so he had a general expertise in brain surgery. He also had a particular interest in Parkinson’s disease. But the handful of foetal transplants that had been done up to that time were performed by large research teams at major medical centres. The teams included basic neuroscientists, immunologists, and neurologists as well as neurosurgeons, supported by large amounts of money from public or private sources. The researchers had years of practice doing the transplants in laboratory animals before they ventured to touch a human being. They had studied every variable that might affect the success of the procedure, such as the right age of the foetus that would supply the tissue, the proper technology for dissecting, handling, storing, and administering the cells, and the right kind of drugs to give the patients to prevent the transplanted tissue from being rejected. The researchers performed brain scans, using advanced technology, to measure dopamine function in the brains of their volunteers before and after the transplants. And they carried out rigorous neurological testing of their volunteers for months before and after the transplants, so that any benefit or harm of the transplants could be assessed. All of this was overseen by university committees composed of doctors, administrators, and ethicists, whose role was to ensure that the volunteers were not exposed to undue risk, and that they were fully aware of those risks that could not be avoided. How was Iacono to replicate all of this, virtually by himself, and without any funds to support the project?

  Iacono was based at a major medical centre – the University of Arizona Health Sciences Center in Tucson – but he would not have been allowed to do the transplant there, for two reasons. First, the operation was outside his recognised area of expertise. (‘I just don’t do stuff like that,’ was how he put it.) Second, there was a general ban on medical research using human foetal tissue at the University of Arizona – a state school in a very conservative state.

  Iacono thought that the best way to overcome these difficulties was to do the operation overseas. He first thought of Japan, which he visited from time to time. But his Japanese colleagues were reluctant to get involved. Then, while in Japan, he met a doctor who worked in a cancer hospital in Zhengzhou, the capital of Henan province in China. The doctor suggested Iacono perform the transplant there: tissue from aborted foetuses was readily available, he said, and regulatory control was lax. ‘It’s no muss, no fuss in China,’ as Iacono put it.

  Travelling halfway around the world for a surgical operation is not unheard of. Plenty of people fly from faraway places to have a procedure that is not available in their home countries. Still, what Iacono was proposing to do was very different: rather than take Truex to an established centre of excellence where the local doctors were experienced in the transplant procedure, he was planning to take him to what, in many people’s minds, could be considered the ‘back of beyond’, and more specifically to a hospital whose staff had absolutely no experience in this kind of surgery. Iacono was going to have to do almost everything himself, so if he was to succeed, he needed to be fully prepared.

  Iacono did in fact prepare himself as best he could. ‘I was learning about immunosuppression, I studied up on the embryology, I read all the papers, and I developed my own technique – I solved millions of problems,’ he said. Still, he did not perform foetal-cell transplantations in animals as the other researchers had done, nor did he go and witness human foetal-cell transplant surgeries at one of the centres that were already doing them.

  One problem stood out as the most challenging. The transplantation procedure involved stereotaxic surgery – that is, the use of a calibrated metal frame attached rigidly to the patient’s skull. By mounting the injection needle on the frame at a specified location and angle, it could be driven into the brain a predetermined distance and the surgeon would know that the tip was in the desired target, the striatum. Iacono was familiar with the techniques of stereotaxic surgery, but such surgery couldn’t be carried out at the Zhengzhou hospital – they simply didn’t have the facilities.

  Iacono thought up a fairly devious scheme to get around this difficulty. In April of 1989, he operated on Truex at the Veterans Administration hospital in Tucson. The operation was a ‘thalamotomy’ – the destruction of part of a brain region called the thalamus. This is a procedure that is sometimes done to alleviate the tremor of Parkinson’s disease, and in fact Truex’s tremor was lessened, according to Kay. But the thalamotomy wasn’t the main reason for taking Truex into the operating room that day. Rather, it was the ‘cover’ (as Iacono himself put it) for a second procedure that he carried out ‘on the QT’ immediately after the first.

  In the second procedure, Iacono inserted three catheters, or plastic tubes, into Truex’s brain, using the stereotaxic equipment that was available at the VA hospital. The tips of two of the tubes were guided into the left and right striatum. Iacono placed the tip of the third cathe
ter in a ventricle – one of the large, fluid-filled cavities inside the brain. It was the left lateral ventricle, which is close to the striatum on that side. This catheter was of a different design than the other two: its back end was connected to a small rubber bladder, or reservoir, that Iacono implanted under Truex’s scalp. Then he sewed up the scalp incision with all three catheters still in place. The idea was that later, in China, he would be able to push the foetal tissue down the tubes and he’d know that it would end up in the striatum or in the ventricle, even without stereotaxic control. The catheters would serve as pre-targeted delivery chutes. What is more, Iacono thought that the inevitable tissue damage caused by the presence of the tubes would actually be beneficial to the transplant: some research suggested that damaged brain tissue releases chemicals called growth factors that encourage cell survival.

  Truex recovered uneventfully from these procedures, and a couple of weeks later the two men set out for China. They flew first from Tucson to Los Angeles. This was convenient for Kay, because the family had temporarily moved back from Boston to Manhattan Beach, where they were overseeing some work on their old property there which they planned to sell. Thus, Kay and Gene had the opportunity to come up to the airport and visit Max and Bob during their layover. Max didn’t look like a typical globe-trotting tourist: besides his obvious Parkinsonian symptoms, his head was swathed in bandages to protect the locations where Iacono had drilled through his skull. ‘He was in pretty bad shape,’ said Kay.

  At the airport, Iacono and Kay had a frank conversation. This is how Iacono recounted it to me: ‘I told Kay, “You know, I may not be able to bring him back.” And she said, “Bob, you’ve got to try …” And I said, “I may not be able to bring him back – even in a box.” She said, “Bob, please try!” So this wasn’t tiddlywinks. And I’m no Texas chainsaw murderer; I’m a very conservative neurosurgeon, by the way.’

  When I asked Kay about this, she at first denied any memory of such a conversation, but later she said, ‘I’m beginning to remember this ‘box’ thing. He probably did say something like that. He is very colourful.’

  The journey to Zhengzhou was a nightmare. Starting in Los Angeles, Truex and Iacono first flew to San Francisco, where they took a China Airlines flight bound for Shanghai. But fuel supplies ran low, and the pilot had to make an emergency landing in Japan. After a long delay they finally made it to Shanghai.

  From Shanghai, they took a train for Zhengzhou. The 500-mile rail trip took 22 hours, mostly occupied by repeated hold-ups as the steam-powered passenger train was forced to yield the track to higher-priority freight or military trains. And there was no food. Train travel in China was difficult at the best of times, but these times were far from the best: on May 4, about 100,000 students and workers had marched through Beijing to protest at government policies, and this unprecedented event had greatly alarmed the government so the entire country was in a state of tension.

  Truex had been in a bad way at the start of the trip, but by the time they arrived at Zhengzhou he was virtually immobile: he could not walk even a few steps. Iacono had to carry him off the train; then he was put on a tricycle and wheeled to a waiting car.

  Neither man had ever been to mainland China before, and Iacono was unprepared for the primitive conditions that existed at the Zhengzhou cancer hospital. There was no heat or hot water, for example, and the equipment was rudimentary. The microscopes, which were crucial for the dissection of the foetal tissue, didn’t even have built-in light sources. Like children’s microscopes in the West, they simply had little mirrors that you aimed at a window.

  Another surprise had to do with money. According to Kay, the doctors, at the Zhengzhou hospital, or the hospital administrators, demanded a substantial fee – she thought it was in the range of $20,000 to $25,000 – to let the operation go ahead. Don said that Max told him the fee was close to the annual operating budget for the hospital. ‘I think they knew what they had,’ Kay commented, meaning that they had Max over a barrel. ‘Bob was a little taken aback.’

  One expectation was fulfilled, however: according to Iacono, foetal tissue was readily available. ‘I’d say, “I need some things to dissect, guys, because I haven’t had any practice in my country, bring me some stuff.” And it would be, “You need foetal? OK, no problem.” And a couple of hours later they’d bring me something, and I’d say, “Where did you find that?” and it was, “Oh, in the dustbin.”’

  In a medical paper describing the case, Iacono said that the samples used for the actual transplantations were obtained in accordance with US National Institute of Health guidelines, which would include obtaining the mother’s consent to the use of the tissue for transplantation. Max told Don that a female gynaecologist rode through nearby villages on a bicycle, telling people what she was looking for. If so, she would presumably have had the opportunity to explain the planned use of the tissue to the women who had the abortions, and to get their agreement.

  Some other research groups who were doing foetal-cell transplants, such as Curt Freed’s, made an effort to tissue-match the foetal tissue to the recipient, at least at the relatively crude level of the ABO system (the system of antigens commonly known as ‘blood groups’, but actually present in all tissues). Iacono did not tell me whether he did this, but it is unlikely that the Zhengzhou hospital had either the facilities or the expertise to carry out such an analysis. If they didn’t, the compatibility of the foetal tissue with Truex’s own tissue would be pretty much a hit-or-miss affair. Iacono simply assumed that the tissue would be a mismatch, and he started Truex on immunosuppressant drugs – specifically, steroids and a drug called cyclosporin. The hope was that these drugs would prevent Truex’s body from rejecting the transplanted tissue, and he would need to continue to take them for the rest of his life.

  Having taken these preliminary steps, Iacono started the transplant procedure, which consisted of three separate operations. On the first day, he took tissue from a foetus that he judged to be 16 weeks old. It’s now known that dopamine cells from foetuses this old survive poorly after transplantation – by this age, they have largely or entirely lost their ability to survive in a new host – but at the time that may not have been so clear. At any rate, having obtained the foetal tissue, Iacono opened Truex’s scalp and pushed fragments of the tissue down the implanted catheter that led to the striatum on the right side. Then he removed the catheter and closed the scalp incision. It was a very brief operation.

  A day or so later Iacono repeated the procedure, again using tissue from a 16-week-old foetus. This time he implanted the tissue in Truex’s left striatum, using a somewhat different technique: he loaded the tissue into a small, spring-shaped metal coil and pushed the entire coil down the catheter into the brain tissue; then he removed the catheter, leaving the tissue and the metal coil in place.

  For the final procedure, Iacono used tissue from a much younger foetus – it was 16 millimetres long, which would make it only five or six weeks old. Strictly speaking, it was still an embryo and not yet a foetus. This age was younger than what is now considered the optimal age for transplantation, and the tiny size of the foetal brain at that age made accurate dissection a major challenge. Anyway, Iacono dissected out the tissue he wanted, broke it up into tiny fragments, injected it into the reservoir attached to the third tube, and squeezed the reservoir to force the cells down the tube and into the lateral ventricle. After doing so, he left the third tube and reservoir in place, because he planned to use it to take samples of Truex’s cerebrospinal fluid at later dates.

  Injecting the cells into the ventricle, rather than into the substance of the brain, was a novel and risky step. Iacono did this with the hope that the cells, once in the ventricle, would secrete chemical ‘growth factors’ that would in turn promote the survival and growth of the cells he had injected into the striatum. He told me that there were animal experiments to support this hypothesis. But the ventricles of the brain are linked together to form a single tortuous wat
erway through which the cerebrospinal fluid circulates. So putting cells in the lateral ventricle was rather like throwing alien water plants into a particular pond in the Everglades: one might expect them to spread widely through the system, with unpredictable and possibly harmful consequences.

  Iacono told me something even more remarkable about the transplants he performed on Truex. He didn’t take the foetal tissue from the brain region that everyone else was using – the substantia nigra – even though that was the location of the dopamine cells. ‘That just shows you my contempt for the dopamine hypothesis,’ he said. Instead, he took tissue from a strip of the brain near the midline, running from near the front of the brain all the way back to the medulla, where the brain narrows down to join with the spinal cord. This zone contains a diverse assortment of cells that use neurotransmitters other than dopamine. As mentioned earlier, Iacono thought that some of these other cells and chemicals played a more central role in Parkinson’s disease than the dopamine system.

  Truex came through the three procedures without any problems, and within a few days Iacono decided that it was time to go home. But that was easier said than done. On May 20, the Chinese government, in response to the increasing unrest and continued demonstrations, declared martial law. All regular forms of transportation were halted. ‘I had to give up all my cash and my passport for several days,’ said Iacono, ‘and they finally dragged four people kicking and screaming off a Russian turboprop [to make room for us]. I was at the point of tears by then. The tyres of that plane were worn down to the Dacron. But we finally got home, and three days later I heard that that very same plane had crashed and killed everyone onboard.’

  Kay added another detail related to her by Max: on June 4, the two men passed through Beijing’s Tiananmen Square in a pedal-powered taxi on their way to the international airport. Just hours later, the massacre began that cost the lives of hundreds or thousands (accounts differ) of students and workers.