Read When Science Goes Wrong Online

Authors: Simon Levay

Tags: #Non-Fiction, #Science

When Science Goes Wrong (6 page)

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 break 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.

After more than a year’s delay, they sent their manuscript to the
New England Journal of Medicine
, because that journal had already published several articles about foetal-cell transplantation for Parkinson’s disease. But the manuscript was rejected. ‘That was funny,’ says Folkerth. ‘I thought this was something that was definitely worthy of being in that particular journal. There seemed to be kind of a pro-transplant point of view in the other articles they had published.’

What Folkerth didn’t know was that her manuscript was reviewed by Curt Freed, a major enthusiast for foetal-cell transplantation and an author of one of those ‘pro-transplant’ articles in the
NEJM
. As he later told me, Freed recommended that the manuscript be rejected. The reason was a concern that, even though it only described what he considered a ‘therapeutic misadventure’, it could bring the entire procedure into disrepute. (Nevertheless, Freed has had his own setbacks with the procedure. Three years after Truex’s death, one of Freed’s patients suffered a brain haemorrhage during the transplant operation; he died a few weeks later.)

The rejection of the manuscript caused another delay, but in 1995 Folkerth and Durso sent the manuscript to another, less prestigious journal,
Neurology
. It was accepted, and it appeared in 1996, five years after the autopsy it described. Folkerth and Durso didn’t name Iacono in the body of their article. ‘I didn’t want to indict the guy, I didn’t want to be too accusatory,’ Folkerth says. Still, they did thank both Iacono and Kay Truex in a footnote, so anyone in the field would have realised which case they were talking about.

Iacono didn’t respond to the
Neurology
article, or if he did his response didn’t get published. But the journal did publish a response from a research team that had begun to do foetal-cell transplants at the University of South Florida in 1993. Evidently, this team, like Curt Freed, was worried that Folkerth’s article would throw the field of foetal-cell transplantation into disrepute, and they expressed their feelings about what Iacono had done in unusually strong language. ‘This is a case of extremely poor tissue dissection,’ they wrote. ‘One wonders why this transplant was performed in China,’ they added, ‘outside of State and Federal regulations, Institutional Review Board oversight, and peer review scrutiny.’ ‘We should not be surprised,’ they concluded, ‘that poor science leads to poor outcomes.’

Iacono never abandoned his conviction that Truex was greatly helped by his transplants, and he rejected the idea that the tissue in his ventricular system caused his death. ‘There weren’t any signs of increased intracerebral pressure,’ he told me. ‘He wasn’t having urinary incontinence, he wasn’t showing signs of dementia, he wasn’t complaining of headaches. He was acting normally, and his wife said he came in and sat down and died. That just doesn’t sound like [ventricular blockage]. His death was officially signed out as a heart attack.’ (Kay says that Max’s death certificate lists only ‘Parkinson’s disease’ and does not mention any immediate cause for his death.)

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