by Benjamin Mee
The speed of the symptoms was alarming, but they were mediated slightly by the steroids she was prescribed, at ever increasing doses, which alleviate intracranial swelling. I still felt optimistic because several new and less-invasive treatments had been developed since she was first diagnosed, and if the first line of conventional treatment failed, I knew there was a range of well-advanced trials, which I had kept in contact with. Before she underwent another craniotomy, I was keen to explore some of these newer, less-invasive methods.
The difficulty with treating problems inside the brain with drugs is the blood brain barrier (BBB), part of the body’s own defenses. This is a physical membrane that restricts blood access to the brain, protecting it from blood-borne infections. Very few things can get past it, but a virus can, and a modified herpes virus was designed as long ago as 1995 to cross the BBB and carry with it an agent that targets cancer cells and kills them. The measles virus and scorpion venom have also been used in this way in experimental trials in the lab, though not in human trials, when I had last contacted them. Probably most promising, it seemed to me, was a German system of delivering iron oxide particles directly to the tumor site by injection, then agitating these particles with the MRI scanner, which is, after all, a giant magnet. This literally smashes up the tumor from the inside, which I liked the sound of. Best of all, it had been used on fourteen human glioblastoma patients in the previous year, all of whom were doing well. I got in touch with the Germans to see if Katherine would be eligible for their next trial.
Our first encounter with the neurosurgeon in Devon had not been promising, however. Obviously anxious, we’d been led through the neuro department to a small room to meet the man who would be overseeing Katherine’s treatment. He looked reassuringly geeky, but then neurosurgeons usually do. He explained that the scan had revealed a recurrence of “abnormalities,” and scrolled us through a 3-D computer graphic of Katherine’s brain, which showed six or seven small black specks across both hemispheres, including inside the corpus collosum, which is the bundle of nerves connecting the two halves of the brain. Around each speck was a small white stain, like a water mark, which he explained was swelling, which would increase the symptoms associated with each tumor site. This was the bit he could alleviate with steroids, but the tumors were too widespread for an operation, certainly at this stage.
I asked if he could send the scan to our doctor in France so that we could have her input? “No,” he said emphatically, without looking up. “That won’t be necessary.” Would he please send it, as she has treated Katherine for two and a half years, and we would be very interested in what she has to say? “No, this is your treatment center now.” Rarely have I had such a strong urge to punch someone’s face in so soon after meeting them. Moments before I had been respectfully listening to a skilled consultant give us his considered opinion. Now I was fighting the urge to snap off his pudgy fingers one by one before hospital security took me away. However, I felt this would have been a bad start to what was likely to be an ongoing relationship. This stubborn, territorial conservatism in someone who held Katherine’s life in his hands was worrying indeed.
Then I asked him about future possible options such as the modified herpes virus, the measles virus, the scorpion venom, and the German iron oxide treatment, all of which had shown promising early results, some in human glioblastoma patients. He shut his eyes, shook his head and said he hadn’t heard of any of them, but that there are lots of unproven trials that seem promising but always come to nothing. Then he looked at me and said, “I’m afraid this is a very dispiriting tumor to treat.” Poor guy.
He prescribed a course of PCV chemotherapy, a three-pronged approach that is effective in reducing glioblastomas in about 20 percent of cases. To a glioblastoma patient, these seem like good odds. I telephoned our French neurologist and asked her to ask her English counterpart for the scan results, which she did, and fortunately he supplied them to her, so I could cross-reference treatment options with someone in whom I had some faith. She agreed with the initial treatment of PCV, so all we could do was wait until the NHS (National Health Service) was ready to start Katherine’s treatment, on 7 January.
I only hoped they knew what they were doing, as these tumors are graded by their growth rate, and a grade 4 glioblastoma can double in size in a week. We had a quietly fraught festive season. It just seemed that no one was moving at the same speed as the tumor.
JANUARY
Katherine’s condition had worsened in the run-up to the chemo, so we were glad when it began. It involved a short infusion and some tablets to take for the next week. By the time the chemo started, she was already debilitated. Her right arm was completely paralyzed, her hand bunching up with the tension of the tendons, and her right leg was beginning to drag. But she could still walk by herself with the aid of a crutch. With chemo there are usually a few days before the effects kick in, but she was weak, and still recovering from the effects of her long-term treatment in France. So, for the next three weeks she spent a lot of time asleep.
Meanwhile, I was still working at the zoo, in between popping back to the house to check on Katherine. Texts on my phone from that time reveal the usual concerns about wages, etc. But one piece of good news was that we interviewed a great candidate for the position of curator of animals. Filling this position was one of the most important conditions for getting our zoo license. We had to have someone who knew exactly what they were doing in all aspects of animal management—after all, we didn’t. And Steve Pilcher came highly recommended from the much respected Newquay Zoo, Mike Thomas’s old stamping ground, and before that he had worked with the orangutans at Jersey for several years. Orangs are among my favorite animals (though it might be a bit far-fetched to imagine them here within the next ten years), and Jersey is one of the best zoos in the world. Steve’s interview went well. Mike Thomas came up for the day—after all, we weren’t even qualified to interview a curator, as we didn’t know what to look for. Mike led the questioning, and Steve came up with all the right answers, until we got to the question of Spar, the elderly, arthritic tiger up in the top enclosure, and whether he should be put to sleep. This is a contentious question, which divides zoological thinking. I knew from the vet that although Spar was wobbly, he was almost certainly not in pain. At nineteen, he was well past his natural life span in the wild, and his obvious frailty had occasionally upset the visitors at the zoo for the last few years. But the vet had told me he had been in Spar’s corner for many years, and there was no reason why he shouldn’t carry on until there was a real medical reason to intervene. Mike happened to disagree, and phrased the question in a way that made it obvious what he thought. Mike may seem avuncular, but he is also formidable, particularly to a younger candidate being interviewed for a senior position like this. The easy thing to do would have been to agree with him, but Steve didn’t. “Well, he’s not in the wild. He’s in a zoo,” said Steve. “No matter what he looks like, if he’s not in pain, I don’t see why he shouldn’t live out his life until the vet says otherwise.” Mike didn’t like this answer, but I did. Apart from anything else, it showed a steeliness that he would need if he took the job.
Steve was married to Anna, another experienced zoo professional, who was currently lecturing at a university master’s course on veterinary science in zoos. When her contract ended in a couple of months, she would make an excellent addition to the team. Both of them were seriously enthused by the potential of the site and brimming with ideas, backed up with the expertise to bring it forward. Suddenly it looked like we had an excellent upper-management duo, ready to take on the enormous challenges that lay ahead.
But in between us offering Steve the job and his arriving, Katherine’s condition worsened considerably. When he arrived in mid-January, I had to tell him the news, and said that while I would liaise with him daily and give him full support on any changes he felt were necessary, my real attention was elsewhere. The situation in the zoo really required everybody�
�s full attention, but with the arrival of Steve, already braced to face a huge task, I had to unload a lot of the responsibility onto him. Handing over to this poor guy, I could see him accepting the strain, but also that he wouldn’t buckle under it. I thought he could do it, and there was plenty for him to do.
On the same day that Katherine started her chemotherapy, an article appeared in the medical journal Cancer Cell, which was not on my usual reading list. Duncan had heard about it through a review in Scientific American, which a friend had shown to him, and had been apparently mildly surprised when Duncan grabbed the brand-new magazine and insisted on taking it away with him. He showed it to me and explained it as I read. Dichloroacetate (DCA) had been used to treat children with a metabolic disorder for thirty years, with few side effects. What a team in Canada had just discovered, however, was that it would also dissolve glioblastoma cells on contact in the lab. Intrigued, they had infected some rats with these tumors, then given them open access to DCA, dissolved in their drinking water. Because DCA, being a very simple molecule, can cross the blood brain barrier, it finds cancer cells, enters them, and destroys them by reawakening the mitochondria. I’ve always liked mitochondria. They are the power plant of the cell, providing the energy, but they are not strictly human. They are descended from bacteria and have their own DNA, which is why high-altitude training kills off populations of them and produces new ones that can metabolize oxygen more efficiently when sprinting at sea level. What I didn’t know was that mitochondria are also responsible for cell apoptosis, that is, the suicide of the cell, should it become infected. Naturally, as the cancer takes over the cell, one of the first things it does is to switch off the mitochondria. But DCA switches it back on. The experimental group of rats in the lab all had massively reduced tumors, and the control group, without the DCA, had great big fat life-threatening ones. So it can cross the BBB, has been tested on humans for thirty years, and it kills glioblastomas.
However, there were no human trials for glioblastoma specifically. It had only just been published, and at the time I was inundated by suggestions for cures from all quarters. My brother Vincent liked the scorpion-venom research, Katherine’s parents advocated eating apricot kernels, and my personal preference was for the German method, which Katherine’s sister Alice had uncovered and researched. If conventional treatment failed, one of the conditions of getting onto this trial was that the patient was not undergoing any other treatment at the time. Katherine’s scan was already on its way to Germany, and I didn’t want to do anything to jeopardize her eligibility. “If it was me, I’d be drinking gallons of DCA,” said Duncan. But I held off for the time being.
Katherine came out of the chemo slowly, and we had to wait a week or so before she could be assessed for the next round. When she came back around, she came back worse. It had weakened her, as it does, but considerably. I only hoped it was having a similar effect on the tumor, but there was no guarantee of that. Her walking was worse, and she had to be supported on her left side, the good side, and the right leg wheeled into position for each step with a hip-to-hip roll of her whole body sideways. Once the right foot was in position, the knee seldom buckled if we kept the angle right. In time this awkwardly encumbered gate became more complicated, when the right foot refused to come up, and had to be flicked by the heel with my own right foot. This meant standing on one leg at a crucial part of the step with Katherine balanced on her own weakening left leg, so we decided it was more practical to get hold of a wheelchair, particularly for outings, which we wanted to continue while ever it was possible. Unfortunately, none of the different branches of the NHS with which we were by now in contact could provide a wheelchair. The application process was too long, and the kind we wanted, with the big rear wheels, was forbidden for triplegics, in case her bad hand slipped down and got caught in the wheel. But these were by far the most stable chairs, able to navigate the steeper unfinished paths of the park far better than the small-wheeled variety, which Katherine’s brothers eventually managed to hire from the Red Cross. This did make things much easier, however, and I took her out into the park as often as I could, for fresh air and to remind her of the wonders that surrounded us.
She had never seen the tigers up close, so one day I took her behind the tiger house, where the three hand-reared tigers, Vlad, Blotch, and Stripe, would come right up to the fence and do their obviously friendly “chuffing” noises, wanting to be stroked. I’d asked Katherine if she’d wanted to do this, and because it’s very much an “off show” area with poor wheelchair access, she’d waved her hand and shrugged, indicating indifference. But it is a profoundly powerful experience to be so near these huge, huge predators, and then to see them behaving just like great big house cats, wanting human contact. Katherine was not immune to this experience, and was visibly filled with wonder at the spectacle, which was lovely to be able to share with her.
Mum and Duncan provided enormous support for us during this time, looking after the children, helping Katherine where they could, and it would have been impossible without them. But as the person closest to her in her daily life, a position I now know to be formally called caretaker, I learned in more detail some of those little rituals she used to carry out with such graceful efficiency herself. Like the folding of clothes. I was dimly aware of it going on during our years together before, watching from the bed and wondering how it could possibly take someone so long to prepare for going to sleep (twenty-two minutes, over the years I’d noticed, was her average from entering the room to entering the bed). Now I understood the process from an insider’s perspective. If you have nice clothes and you care what you look like, the key, it seems, is to treat them carefully and put them away after using them, rather than just leave them on the floor (my clothes are generally sloughed straight onto the floor and stepped out of, ready, often, to be reused the next day).
Though it was an outward and shocking sign of her increasing disability, with potentially sinister implications, caring for Katherine became in some ways the best part of the day. It gave us a chance to be together in a way that we couldn’t manage while she had been the human dynamo in the office and the home, spinning more plates than I even knew existed. Those intimate hours in the daytime and at night as I helped her to the toilet, washed, fed, and dressed her were spent in laughter, and became a welcome break from my more public duties as a new zoo director.
As Katherine became more disabled, I spent more of my time with her. Initially I could get her up, washed, dressed, and breakfasted by about ten o’clock, and then leave her sitting or reclining somewhere with a stack of reading matter and remote controls. But this felt like abandonment, because for someone as naturally busy and as engaged with the outside world as she had been, this enforced leisure was a torture. I popped back as frequently as I could, inevitably delayed by myriad queries and problems that beset any novice proprietor of a run-down zoo. We were told that if, somehow, the tumors were successfully removed this time, her movement and speech might return, but again they might not.
In the meantime I began learning about the fastidious art of eyebrow plucking. If you need a magnifying glass to detect a bristle of an eyebrow, I suggested, then you probably don’t need to pluck it. Someone across the room, or even a couple of feet away, won’t be able to see it. But this cut no ice with Katherine. After careful positioning of mirrors, tweezer, and optical equipment enabling the detection of actual bristles, came the technique. This is no snatch and grab, but a much more deliberate and torturous method. Grip the offending millimeter of hair firmly with the tweezers, and slowly ease it out in what for most men would be an eye-watering agony. But female grooming breeds stoics, and never a flicker crossed even the good half of Katherine’s face as I reluctantly conducted this torture.
Suitably groomed and plucked (Katherine, that is, not me), we arrived at the hospital for our next appointment—and had the most chilling conversation of my life. Our appointment with the oncologist to discuss Katherine’s progres
s, and therefore prognosis, had a surreal breeziness to it, as the life of this most beautiful person was discussed and seemingly dismissed in a shitty little back room painted NHS blue, next to the toilets in the oncology waiting area. The big, doe-eyed oncologist began by discussing plans for the next round of PCV, but I was concerned that it had taken such a lot out of Katherine that we needed to be sure it was working before we continued, otherwise she would suffer needlessly, but also because she would be semi-comatose and unable to report symptoms at a very critical time, when we might need to switch treatments. It was a good thing I asked. “Well, actually, I have to say I don’t think it is working,” she said. “It reduces tumors in about twenty percent of cases, but normally by now we’d expect to see some slight improvement. And as you can see”—gesturing to Katherine—“things have got worse.” Katherine sat in her Red Cross wheelchair, smiling her half smile, taking it in or not, shrugging a bit, unable to communicate the million things she must have been feeling inside. Then the oncologist turned to her. “You don’t really want to be feeling poorly for a couple more weeks do you?”
Katherine, defunctionalized, unable to speak, probably unable to grasp the sheer enormity of what had just happened, smiled and blinked, and shrugged. It took me a while to grasp it too. I looked around the room. The medical student had clearly been briefed that this would be a death conversation. She couldn’t do eye contact. The wide-eyed male nurse from Macmillan Cancer Support said nothing, but provided a foil for the knowing asides from the oncologist. I asked the oncologist if she’d read the DCA article I had forwarded. She rolled her eyes with a “silly me” smile, and said, “Oh, I haven’t had time.” Cancer Cell, I suggested, was a fairly serious journal that, one would have thought, would appeal to oncologists. “Mmm. It’s a mitochondrial cell-apoptosis route,” she said aside to the Macmillan nurse, who now seemed to be present more as security than for any benefit to Katherine. They laughed briefly. How silly of us to hold out any hope for that.
