I asked them both to give me a few minutes with Tom, so I could kiss him goodbye. How many times had I done this, not knowing whether it would be the last time? Too many to count.
“You know I love you, and I am with you always,” I whispered in his ear as I stroked his cheek. “I’m gonna take a break while we wait for our phagey friends, and I’ll see you later.”
Okay.
If Tom’s spirit was journeying, as the girls had suggested, I just prayed he could find his way back. He was still motionless as a mummy in his shroud of a gown, interwoven with IV lines, drain tubes, patches, and sensors. No perceptible ka, and he’d need it to fight off the enemy within. I thought about Khalid and what a patient teacher he’d been, and a lifesaving guide far beyond the pyramids, when we’d depended on him to help us navigate Tom’s medical crisis in Luxor. What was that myth he’d told us about Ra, the sun god, descending into the underworld, battling demons and gods who opposed him? Apophys, the god of chaos, would partially swallow Ra, leading to the setting of the sun each night, and then would spit him back out at dawn, for the sunrise. At this point, tonight’s sunset could easily be Tom’s last. He needed to hold on for another dawn.
21
MOMENT OF TRUTH
March 15–16, 2016
When the call came at around seven p.m., I nearly fell off my chair. Michelle and I were sipping our second glass of Chardonnay on the back patio, watching the sunset, and trying to keep our minds off the inevitable. It was Tom’s favorite time of day: dusk. Not quite light, and not quite dark, like the in-between netherworld he was suspended in. I’d fed the kitties and reheated some tamales that one of our fellows, Argentina, had dropped off earlier in the week. The girls and I had tried to share cooking duties, but the days were exhausting and sometimes Tom’s bad turns meant that we stayed longer than we planned. So, when friends and our students offered to cook for us, we gratefully accepted. One of our postdocs organized a schedule, and people would drop off casseroles at the hospital or our house. Nepali and Indian curries, Filipino spring rolls, Mexican tamales—a world of foods and such generosity, comfort food in the truest sense.
I poured that second glass of wine for us both. Nothing was going to take the edge off this day, but it was time to at least hit pause on the caffeine. My cell phone trilled, and I answered with a bark that shattered the peaceful quiet. Michelle winced. It was Carly.
“It’s time,” she said excitedly. “The phages are finally ready!”
She quickly brought me up to speed on what had transpired over the last few hours. For his part, Tom had kept peeing, which meant kidney dialysis was again deferred until the next morning. Whether Tom could last that long was anybody’s guess.
It had been Chip’s turn to get antsy; he had called down to the pharmacy every hour as the late afternoon ticked by. Chip had once told me that he didn’t like patients to have procedures in the evenings because there were fewer staff around, which is why I had started to suspect that phage therapy wouldn’t be started until morning. But by the sound of things, Chip had overruled himself. He told me later that he was too worried that Tom wouldn’t make it until morning. There really wasn’t a minute to lose.
“So,” Carly said, “do you want us to wait so you can get here?”
It was about seven o’clock, and the view of Highway 5 from our backyard still showed a trail of red lights running south as rush hour dragged on. Bloody hell. How could I have worked so hard to make this moment happen and now miss it? I was crushed that I wasn’t there, but delaying the phage therapy was not an option. It was go time. Carly and Frances would keep texting me so I could follow the play-by-play. If things started heading south, I would call an Uber and get there ASAP.
In a sudden streak across the weary sky, a peregrine rocketed by and perched in the palm tree in the neighbor’s yard, scoping out the back slope for pigeons and ground squirrels. Tom would have appreciated the falcon’s familiar presence at his favorite time of day. I was struck by a harsher truth that was oddly reassuring as well. For every prey, there is a predator. In the peregrine’s case, with the ability to fly as fast as two hundred miles per hour, it is the perfect predator. Now we were waiting for another perfect predator to do its work.
Over the next few hours, Bed 11 became the busiest room in the ICU, but in a good way for once. At least ten doctors appeared seemingly out of nowhere, representing a full range of medical disciplines: infectious disease, pulmonary medicine, GI, nephrology, cardiology, and interventional radiology. In addition to those on duty, some TICU staff and a clutch of residents and fellows who were on rotation hung out at the door when they were not needed elsewhere. Cara Fiore, the FDA official who had coordinated the approval process, had called Chip from her son’s hockey game in Maryland to check on the patient. No one wanted to miss being a part of the action. History was being made, no matter what the outcome—and no matter what time it would finally happen.
Frances and Carly were at their dad’s side, taking turns holding Tom’s hands. Martin, our holistic healer, had arrived earlier and gave each of them a hug. He had known them both since they were teeny-boppers. From his home in Toronto, Robert texted to tell me he was “tuning in” by making a psychic connection to Tom. Around the world, countless numbers of our friends and colleagues were praying, lighting candles, sending energy, and checking Facebook for updates. I later learned some had been avoiding checking Facebook in recent days because it seemed inevitable that Tom was dying and they didn’t want to see the dreaded post that would make it real.
At a little after seven, Dr. Sun, the manager of the investigational pharmacy’s drug service, and his resident, Minh, finally appeared at Tom’s doorway, carrying a large foam box that had a biohazard sticker emblazoned on top. An unassuming man, Dr. Sun was not used to being the center of attention. He blushed when several of those in the room gave a quiet cheer, greeting him with the enthusiasm that one might give the ring bearer at a royal wedding. He stepped toward Chip and, with a light ceremonial bow, handed him the box.
Chip pored over its contents, checking that each phage was correctly labeled on the exterior of a vacuum-sealed plastic bag, which had been carefully kept at four degrees Celsius. The plastic was dark brown to protect the phages from the light, since they are sensitive to UV rays. Randy counted out one syringe for each of Tom’s three drains that had tested positive for Acinetobacter, as well as three syringes for the buffer solution.
“We need Martin to bless the phages!” Frances cried out suddenly. Carly nodded in agreement. Martin stepped forward, approached the open box, and laid both of his huge, gloved hands on the brown plastic bag of phage prep. His figure was imposing; he was almost as tall as Tom. He closed his eyes and muttered an unintelligible prayer. Several of the physicians bowed their heads and murmured an awkward “Amen,” while others gaped or looked away. The room felt charged with electricity, all focused on the phages now, as if every molecule of energy focused on Tom’s recovery had been harnessed into a laser beam.
Randy handed the syringes of buffer and phage to Dr. Picel, the IR doc who had personally inserted all of Tom’s drains and his feeding tube. He literally knew Tom inside and out. Just then, Carly whipped out her smartphone and snapped a photo of Chip and Randy at bedside, smiling nervously for the camera. Then she blasted the room with the chorus from Survivor’s song “Moment of Truth.” Although this was by far the scariest moment Carly and Frances had likely ever experienced, I marveled that they welcomed it with their dad’s offbeat sense of humor. He would have roared with laughter, but his spirit was somewhere else, deep in the ether. As everyone in the room inhaled, Dr. Picel injected the buffer and then the phages into each of the three drains. The silence was punctuated only by the muted beeps and wheezes of Tom’s monitors and the infernal drip of the ventilator hose, until Frances asked the question everyone was thinking.
“What happens now?”
“We wait,” Chip responded. “We wait, and hope that the nex
t twenty-four hours are the most boring we have ever had.”
That would depend wholly on how boring the next twenty-four hours were for the phage and Acinetobacter as they squared off in their own fight for survival—not against Tom but against one another. The scientific literature and high-tech electron micrographs suggested anything but a boring encounter.
Phages don’t so much prowl for their prey as bump and sniff what they encounter to find a matching host bacteria. So it can take them a while to find a match if the concentration of their prey is relatively low. In Tom’s case, his massive infection was a phage’s smorgasbord. Acinetobacter was everywhere. An all-you-can-eat buffet. It was especially concentrated in the pseudocyst and nearby pus-filled abscesses where some of the drains had been placed, so that’s where the first phages were injected for a direct hit. But the micro lab had also cultured it from his lungs and periodically from his blood.
In a typical phage strike, once the phage locates its target bacteria, it moves in for the kill. A recent study even found that phages cooperate in their attack, with the first engaging in a suicide mission that weakens the bacteria’s defenses for the ensuing attack from the rest. But once the phages have put a dent in their target bacteria host population, bacterial mutants of A. baumannii that weren’t vulnerable to the cocktail then proliferate. Those surviving bacteria are, by definition, resistant to the cocktail in use and thus pose a threat of reviving an overwhelming infection. The easiest way for bacteria like A. baumannii to become resistant is to simply delete the gene that encodes for the phage’s receptor. With the receptor modified, the phage can no longer attach to its host.
Tom’s A. baumannii was one of the nimblest superbugs on the planet, top-ranked not only because it picked up so many antibiotic resistance genes, like Tom’s had, but because of its overall hardiness. Extreme heat, cold, or other environmental assaults? No problem, A. baumannii has evolved to survive. Chemical disinfectants and other sterilizing efforts to clean medical equipment and hospital settings? A. baumannii’s biofilms are impervious to some of them. Plus, it has evolved what have been described as “tiny fingers” to hold on to those smooth, slippery surfaces. Tom’s Acinetobacter had also clearly beat out competing bacteria in Tom’s microbiome. Unlike the mild-mannered A. baumannii I’d first encountered decades ago as a student, this one wasn’t wimpy anymore.
But the phages didn’t need to be superstars to score. With the element of surprise on its side, this first-round draft of phages, injected directly to the infection sites, could deliver a blow to the vulnerable A. baumannii that could maybe knock the infection back just enough for repeated rounds of phage reinforcements to break its grip and give Tom’s immune system a fighting chance.
Invisible to us but invincible, we hoped, the phages were already now in pitched battle against the A. baumannii. In this theater of war where the action changed in a matter of minutes or hours, our field reports from the trenches, our only intelligence from the frontlines, would come in what suddenly seemed a primitive mode of communication: blood tests and analysis of the “output”—the gunk from Tom’s drains—and from lab cultures and the digital displays on the monitors that crowded Tom’s bedside, tracking his vitals. The generals in our war room—Chip foremost—had to figure out how to stay one step ahead of the enemy, working off information that was already hours old by the time it was decoded.
With the arrival of the phages and the start of treatment, it was tempting to imagine that the tide was turning and Tom might pull through. But when I closed my eyes to try a visualization practice Robert had suggested, one in which waves of phages crushed the A. baumannii, the image stuck in my mind was that of a killer wave about to crush my surfer dude.
Through the night, Tom received round after round of the Texas phage cocktail, one every two hours, and there were no signs of adverse reactions. I stayed home but might as well have gone back to the hospital, as much as I called in to the TICU nurses’ station to talk to his night nurse or anyone with eyes on Tom. Finally, well before sunrise, I took off for the hospital and was back by Tom’s side.
As part of the protocol, samples from Tom’s drains were to be taken every twenty-four to forty-eight hours and sent to the CPT and the Navy labs. For each round, the A. baumannii first had to be isolated and cultured by the micro lab, then sent along to the Navy and Texas labs. On their end, the labs would test to see if the phages in use were still active against successive isolates of A. baumannii.
I peered at Tom closely, studying him for some sign, anything, that would reveal if the phages were working. But I could see no change in his appearance. His labs looked the same as the day before, with the exception that his white blood cell count—the blood’s infection fighters—had increased and his hemoglobin had dropped, so he was given yet another blood transfusion. Chip explained that this was expected; Tom’s immune system had detected an invader. We could only hope that this was a mild episode of friendly fire.
Tom’s vital signs remained relatively stable, although “relatively” at this point was nothing like “good.” He remained in a coma. And he needed every bit of life support to breathe and keep him this side of a flat line.
Joe Ix, my nephrologist colleague, stopped in to check in on Tom’s progress. Tom’s hourly urine output had increased somewhat, to 60 milliliters per hour.
“Your husband pees like a racehorse,” he grinned. High praise from a nephrologist.
“Yeah, and by now, he probably costs more than one, too,” I replied with a tired smile. So far, so good. Joe decided that Tom had avoided dialysis for yet another day, and he would check in again tomorrow.
The Navy phages were scheduled to arrive by evening, with the pharmacy team on standby to prepare them for IV administration. As Chip had warned, this was infinitely more dangerous due to the potential for septic shock. I knew how fast that could happen, since I had seen for myself how suddenly Tom had gone into shock when his pseudocyst drain had slipped two months ago.
We were entering even more uncharted territory now. Over the next few days, Tom’s life would hang in the balance. We all knew that one of two things would happen soon.
He would recover, or he would die.
22
THE BOLD GUESS
March 17–18, 2016
For all the hoopla, the do-or-die moment of injecting phages into Tom’s bloodstream seemed oddly anticlimactic. I half expected him to open his eyes or to sit bolt upright, but there was nothing of the kind. Of course, that was unrealistic to expect. That’s how it would play out on TV. Tom had been comatose off and on for nearly two months before the Texas cocktail had been injected into his abdominal catheters Tuesday night. Now, forty-eight hours later, and with much less fanfare, Randy Taplitz administered the first dose of the Navy IV phage cocktail to Tom. We both held our breath as the phage dilution surged through the IV line embedded in Tom’s frail arm.
We both knew this was the riskiest moment thus far, and silly as I felt doing it, when no one was looking I took a cue from Frances and blessed the phages—just put my hand on the bag and said a little prayer. It couldn’t hurt. While I prayed, I imagined the phages swimming to the infected abscesses, evading whatever Tom’s beleaguered immune system might throw at them, and dodging the liver and spleen’s filtering system that Carl’s work had shown to clear phages from the bloodstream. Cocktail notwithstanding, it was not your average happy hour. Tom would have joked, Make mine shaken, not stirred! In my mind’s eye, I lifted my imaginary glass and made a toast. Here’s to your health, Hon—please please live long and prosper.
The procedure itself was remarkably simple—so simple that Randy called the pharmacy to double check, then taped the instructions to the wall for the rest of the team. I watched her press the plunger on the IV syringe, and thought of the microscopic “living syringes” flooding in to inject themselves into the Acinetobacter. Tom would have laughed—he’d been on the end of an experimental syringe before. He’d been just a kid in San D
iego at the time Jonas Salk was conducting his polio vaccine research, and Tom was one of the schoolkids who received the experimental polio vaccine. He’d told the story of being in third grade, lining up for the shots in the school auditorium. The needles were huge, at least to an eight-year-old’s eyes, and full of pink fluid. This was before they had perfected the polio vaccine, and while the study was successful in proving it could work, there were some adverse side effects for some children. Tom had come through that well enough, and the polio vaccine had gone on to nearly wipe the disease off the planet as a threat to generations since.
Whatever came of Tom’s current encounter with an experimental treatment on the pointy end of a syringe, I just wanted him to live to tell the tale. That story would have to wait, and it might not be Tom’s to tell if the phage therapy didn’t work, or didn’t work fast enough.
As ubiquitous as phages are in the environment and in our bodies, from birth to beyond the grave, and as integral as they are in the various microbiomes, surprisingly little is known about how they operate in our bodies. It was easy to think of phages simply as the good guys, predators policing our innards, picking off bad-guy bacteria like Acinetobacter as just part of a day’s work. That’s the mission we’d assigned to these phages. But the selection process for our phage cocktails had been so painstaking precisely because the gazillions of other phage types—an estimated 30 billion or so that we absorb into our body every day—include vast numbers with no interest in Acinetobacter, or at least not in Tom’s particular strain.
All Tom’s team could do was construct a cocktail of phages with promising characteristics, but no one was sure how they would perform in vivo on this war front. Or if they’d be able to survive long enough to meet the foe.
The Perfect Predator Page 23
