When Science Goes Wrong

by Simon Levay

  Truex finally rejoined his family in Manhattan Beach. He was very tired, but hopeful that the cost and exhaustion of the trip would pay off for him. And, according to Kay, he had good things to say about all the people who cared for him in China. In that connection, Jim Slosson added a fairly implausible detail that he supposedly learned from either Truex or Iacono. During his hospital stay in China, Slosson said, Truex spent his time running up and down the corridors after the Chinese nurses. ‘The good-looking ones,’ Slosson added, with a wink.

  Before long, the family moved back to Boston. According to Iacono, Truex’s condition improved greatly over the 18 months that followed the surgery. Already at six weeks his facial expressions were livelier, and soon thereafter his speech and his gait improved. By 15 months, he was able to resume normal daily activities, Iacono told me, and he even began running again in order to coach one of his sons. Iacono described the overall improvement as ‘so dramatic.’ He did, however, offer one caveat, saying that no one had checked to see if the immunosuppressant drugs that were used to prevent rejection of the grafted cells might themselves have a beneficial effect on the symptoms of Parkinson’s disease. When I asked him to expand on this far-from-the-mainstream notion, Iacono clammed up. ‘I’m not going to tell you that stuff,’ he said. ‘I have to write my own book about that.’

  Iacono wasn’t alone in his belief that Truex did well after the transplant: other people who knew Truex before and after the operation were of the same opinion. ‘There was nothing dramatic or immediate,’ said Kay. ‘I remember, I think it was about a year after surgery, Bob called to see how he was doing, which he did periodically, and I said, “You know what, I think Max is doing very, very well, because it just occurred to me that for about the last three weeks to a month I haven’t been doing anything for him, he’s been doing everything for himself.”’

  Don Truex agreed. ‘His facial expressions were better, his speech was better,’ he said. ‘There’s no question in my mind that he was substantially improved.’ Jim Slosson also said that Max was better after the transplant.

  Iacono was impressed enough with the results that he took other patients to China for similar transplants, but he performed the surgery in a more modern hospital in Shanghai rather than in Zhengzhou. He described some of these cases, including Truex’s, at several scientific meetings that he attended.

  In the second year after the surgery, Truex visited a neurologist by the name of Raymon Durso, who is a specialist in Parkinson’s disease at the Veterans Administration hospital in Boston. Durso also has an academic appointment at Boston University Medical School.

  ‘I think I saw him a total of three times,’ Durso told me. ‘He definitely said he was improved. However, when I went over the history, his doctors had, for example, added Deprenyl, and so I was never willing to attribute his improvement to the surgery.’

  The United States’ Food and Drug Administration (FDA) approved Deprenyl for the treatment of Parkinson’s disease in the same month that Truex received his transplants. In some patients it significantly alleviates the symptoms of the disease, and it can also cause euphoria, so that a person may feel and act more upbeat even if the physical symptoms are unchanged.

  The last time Truex visited Durso was in March of 1991, a year and ten months after the trip to China. Durso says that Truex seemed quite well at that time, aside from some swelling of his ankles. Such swelling can be caused by mild kidney failure, and Durso confirmed this diagnosis by means of blood tests. Chronic mild kidney failure is a common finding in people who are treated with immunosuppressant drugs.

  Although he seemed reasonably well to Durso, Truex evidently did not seem well to himself, because right around that same time he began telling Kay that he was dying. Kay didn’t take him seriously at first, but he was insistent. When she asked him what made him say that, he replied, ‘I just know, I just don’t feel the same, I just know I’m dying.’ Then, over a period of ten days or so, Max began giving Kay specific instructions concerning his death. ‘He told me about his life insurance policy,’ Kay says. ‘He had me go into Boston and sell off some stocks that he didn’t want to cause problems afterwards, and he had me write down that he wanted to be cremated, and where he wanted his ashes.’ He also gave Kay power of attorney for medical matters, and told her that he did not want to be resuscitated if the question arose. Kay realised that Max was very serious about his belief that his life was ending, even if he couldn’t verbalise the reasons.

  Two weeks after the visit to Durso, on the morning of Sunday, March 24, Kay woke to find that Max was already out of bed. She got up and went downstairs in her nightgown, and she found Max in the living room. This is her account of what followed. ‘I asked him if he wanted me to fix him some breakfast, but he said, “No I’ve already had something. I’m kind of tired, I think I’m just going to lie down on the couch for a while.” I wasn’t feeling well either, so I lay down on the other couch. The kids weren’t up yet. I was dozing, and then I heard him moving around, and it was like he caught himself on the arm of the couch, so I got up and I said, “Do you need help, are you OK?” He said the strangest thing – it was like something changed, something was going on in his head – and he said out of the clear blue, “I think I can still pee in a can.” And then he just kind of slumped. I looked up, and my son John had come down the stairs and was right there. By then we were in the doorway between our living room and our kitchen, and I said to John, “Grab a chair quick, Dad’s going down.” So he came over and we got Max into a chair, and he kind of slumped over and it was like he was snoring: a puff and a puff and a puff and then a rush of air out of his lungs. And I said, “John, stay with Dad, I’m going to get dressed, I’m going to take him to the emergency room, I don’t know what’s happening.” And I came back down as soon as I could and said, “How is he?” John said, “Fine, Mom, he’s sleeping.” But he wasn’t sleeping.’

  Kay called an ambulance, but it took 20 minutes or so to arrive. Kay knew that Max was dead. Gene and Mindy came downstairs, and the four of them talked about what had happened. When the paramedics finally arrived and began to insert a tracheal airway, Kay remembered what Max had told her just a few days previously, and said, ‘He doesn’t want this.’ The paramedic said, ‘Do you have something legal?’ and Kay explained about her power of attorney.

  Then the paramedic took out the tracheal tube and said, ‘He’s been gone for some time, it would have been much too late anyway. I was doing it mainly for the children’ – presumably to assure them that everything possible had been done to save their father. The ambulance crew left, after telling Kay to call a funeral home and have them collect the body.

  Even though she and the three children were in a state of extraordinary shock and grief, Kay remembered something else that Max had told her during his final days, which was that, when he died, she should contact Iacono because he would want Max’s brain saved for scientific study. And when Kay Truex called Iacono later that Sunday to let him know that Max had died, he was indeed very eager to have Truex’s brain examined. He knew that it might be possible to detect the presence of the transplanted cells. To show that these cells had survived for nearly two years after the transplant surgery would be an important scientific finding, and it would provide a partial validation for the foetal tissue treatment. There was no reason to suspect, at that point, that the transplants had anything to do with Truex’s death – he might easily have died from some other unrelated condition such as a heart attack. So, after some calls between Iacono and Dr Durso, Kay was asked to have Max’s body taken to the New England Medical Center.

  She did arrange for the funeral home to take him there, and Kay and the children followed the hearse in their own car. When they got to the hospital, the staff, who had been alerted to the situation, had Max’s body taken to the morgue, and Kay returned home. In the face of her own and her children’s grief, she had to alert other members of the family. She called Don, leaving it to him to brea
k the news to his and Max’s mother – a widow of 10 years and now the mother of two sons who had died suddenly and unexpectedly.

  I asked Kay whether Max’s last words, ‘I think I can still pee in a can’, meant anything to her. She said that it seemed to be just a random fragment recalled from his childhood. ‘I know that his mother had told me that she potty trained the boys by having them pee in a can,’ she said. ‘They liked the noise.’

  In the regular way, brain autopsies are leisurely affairs. Within a day or two of the person’s death, the brain is removed and placed in a bucket of formaldehyde, where it sits for several days or weeks until it has hardened sufficiently that it can be easily sliced and studied.

  But this was not to be the regular way. Iacono wanted to use very sensitive chemical procedures to detect the presence of the transplanted cells. These methods identified certain enzymes present in those cells – enzymes that were responsible for synthesising the particular neurotransmitters that those cells produced. For these procedures to work, the brain tissue had to be as fresh as possible.

  Iacono said that he asked Durso to arrange for the brain to be removed that same day. Durso began making phone calls to locate someone who would be able to do the procedure. He tried several neuropathologists who he knew at the Veterans Administration hospital, but because it was a Sunday, and already late in the day, he wasn’t able to track anyone down. Then he tried to page other neuropathologists around town, and finally, during the evening, he reached Rebecca Folkerth.

  Folkerth was on the staff at the New England Medical Center, but she wasn’t on duty at the hospital that day, or even on call. ‘But I was one of the crazy foolish people who leave their beeper on all the time,’ she told me. ‘I answered my page on the Sunday night and I said, “OK, I’ll come and do this autopsy.” It sounded like Durso was having trouble getting anyone to help him.’

  Folkerth reached the hospital around 9pm. ‘Once I got there, I got a call from Dr. Iacono,’ she says. ‘He told me the whole history and said, “Can I ask you to take some of the tissue fresh and freeze it?” I said, “OK, fine.” It’s not the usual thing – we usually put it in formalin and let it harden for a couple of weeks.’

  So Folkerth donned scrubs and a face shield, identified Truex’s body, wheeled it out of the cooler, and began the procedure. First, she placed a block under Truex’s head, raising it a few inches to make it more accessible. Then she took a scalpel and made a long, curving incision in his scalp, starting behind one ear, passing over the top of the head, and ending behind the other ear. This separated the scalp into front and back halves. She took hold of the front half and pulled it down over Truex’s face, and then she pulled the back half backward and down over his neck, leaving most of his skull exposed. Then she took a power saw and began to cut off the entire top of Truex’s skull. Even with the power saw it was hard physical work, and it took about 30 minutes. In usual circumstances, the job is often left to the diener, the technician who runs the morgue.

  Having removed the skullcap, Folkerth cut the cranial nerves and the blood vessels that supply the brain, and then sliced across the top of the spinal cord so that Truex’s brain was now entirely separated from the rest of his body. Being in its natural, unhardened state the brain was jelly-like and difficult to handle, but Folkerth placed it in a dish, took a long, broad-bladed knife, and sliced the brain as best she could into a series of slabs, each about a half-inch thick.

  Up to now, Folkerth hadn’t noticed anything unusual about Truex’s brain. ‘But as I was cutting it,’ she told me, ‘I made this observation, “Gee, look at this strange stuff in the ventricles, in the third and fourth ventricles, and in the lateral ventricles also.” I thought, “Isn’t that odd?” and I took a bunch of pictures. And I thought, “That looks like cartilage; isn’t that weird!” Even to the naked eye it looked like cartilage, and there were hairs – you could see them, just eyeballing it – the gross pictures are extremely dramatic.’ By ‘gross’ pictures, she meant the pictures she took with a regular camera, as opposed to pictures taken through a microscope. She didn’t mean that they looked gross, though in fact they did.

  Brains don’t usually contain cartilage or hair, of course. Nor bone or skin, which she later discovered were also present. ‘You could see the hair shafts,’ she went on. ‘So I knew there was something very strange about this right away. Oh, this was the most strange thing I’d ever seen, and at this point it was the middle of the night. I was the only one there, looking at this case and thinking, “What the hell is this?” It was creepy. So here I am taking these pictures and thinking this is some mistake; this is a tumour – a teratoma.’

  A teratoma is a tumour derived from embryonic stem cells that retain the capacity to form many or all of the body’s various tissues. Most commonly, teratomas form in the ovary, but they can be found in other places and in either sex. Teratomas contain a chaotic mixture of tissues, which can include cartilage, skin, hair, bone, gut, retina, brain, glands, even teeth. It’s as if the tumour is trying to form a foetus, but without any conception of how the various tissues are supposed to be arranged.

  It looked like something similar had been happening inside Truex’s head. Lumps of glistening cartilage lined the floor of one of the ventricles. Part of one of the lateral ventricles was completely filled with a waxy, skin-like tissue. The fourth ventricle, which is located in the brainstem near nerve centres concerned with breathing and other vital functions, was packed full of hair and other tissues, so much so that some of the surrounding brain structures were compressed and discoloured.

  A teratoma? Folkerth knew that that was exceedingly unlikely. Teratomas can on rare occasions occur in the brain, but if so it would usually be in the brain of a newborn infant or young child. A brain teratoma in a 53-year-old man would be a diagnosis of desperation. Then Folkerth remembered the case history that Iacono had recounted to her – the Parkinson’s disease and the transplants. And as she examined the brain slices further, she began to figure things out. In the left striatum, she found the metal coil that Iacono had used to convey the second transplant into Truex’s brain. And she saw the catheter that Iacono left in place after the third transplant. The tip of the catheter was still located in the left lateral ventricle. ‘I thought, “It can’t be a tumour; it’s the tissue they infused in there.” There was no other explanation.’

  Folkerth froze some specimens of tissue for later microscopic examination, as Iacono had requested. She put other parts of the brain in formalin. Then she reassembled Truex’s head as best she could: She replaced the skull cap, pushed the scalp back over it, and sewed the incision roughly together. Having returned his body to a more-or-less lifelike appearance, she wheeled it back into the cooler. The next day it was collected by the funeral home, and later it was cremated in accordance with Truex’s wishes.

  This whole experience left a big impression on Folkerth, and so over the next few months she devoted a lot of her free time to analysing the tissue samples from Truex’s brain. In the left and right striatum, where Iacono had deposited the tissue from the two 16-week-old foetuses, she found no surviving cells from the transplant, only scar tissue. This was consistent with findings from other research groups, who have reported that tissue from foetuses this old has a very low chance of surviving the transplantation procedure. Folkerth concluded that the reported improvement that Truex had experienced was not due to the presence of any transplanted nerve cells in his brain. Either just the damage caused by the injections had a beneficial effect, which didn’t seem terribly likely, or some other factor, such as the new drug that Truex received, was the reason.

  What about all the weird tissues in the ventricles? These presumably arose from the tissue that Iacono had dissected from the very young, five- to six-week-old foetus and had injected into the left lateral ventricle. Folkerth believes that Iacono mistakenly included some tissue that was not from the embryo’s brain at all – tissue from just outside the brain that normally would
have developed into the overlying bone, cartilage, skin, and hair. Those cells could have drifted through Truex’s ventricular system, found some attachment point, multiplied, and followed their own normal developmental pathway, unaware that they were now in a highly inappropriate location.

  I asked Folkerth whether she thought that the blockage of the ventricular system was the cause of Truex’s death. ‘In my heart of hearts, yes,’ she said. ‘I think that was the cause, but it wasn’t a complete autopsy so I can’t rule out a heart attack, pulmonary embolus, or something like that. The story that his wife told me made it sound like he had respiratory failure. I think he had gradual changes in the brainstem [where breathing is controlled] that couldn’t be compensated for any longer, because we saw a lot of chronic changes, microscopically.’

  Iacono had been the initial driving force behind the autopsy, and it would have been natural for him to participate in publishing the findings that emerged from it. In fact, at a scientific meeting three months after Truex’s death, he announced that the results of the autopsy were ‘pending’. But later, Iacono seemed to lose interest in having the results published. And that wasn’t too surprising, perhaps, because the findings suggested not only that two of the transplants had failed to survive, but also that the third had survived only too well, and had quite likely caused Truex’s death.

  Still, Raymon Durso and Rebecca Folkerth felt that the findings should be published, because at that time there were only one or two autopsy studies of foetal transplant recipients, and the results in Truex’s case seemed to offer an important warning to researchers in the field. So, after some delay, Folkerth and Durso decided to write the paper on their own without Iacono. For the clinical details of the case they would rely on what he had told them and what he had reported at that scientific meeting.