The Perfect Predator

by Steffanie Strathdee

  Reading the risk, mining the data, and getting it right. At the moment, Tom’s life hung in that balance.

  It wasn’t like Forest to call late at night, especially on a Sunday, but when he called Jeremy Barr, his postdoc fellow, and told him about Tom’s situation and the urgent need for their help to purify the Texas phages, Jeremy understood the rush. It was all hands on deck. Forest had called with a number of questions, but they boiled down to this. Was Jeremy confident that their particular phage prep process could purify the phages to the FDA level for human use? That hadn’t been done before. And could they do it in twenty-four hours?

  Jeremy did a quick mental calculation of the hours required for the process, the number of phages to be purified and prepped for use, and the level of purity required to meet the FDA standards. Yes, it was possible. To do this for a critically ill person instead of the usual basic science experiments made it a little terrifying, but that didn’t change the time required, and this was something he knew well how to do. This was his specialty. Jeremy had come from Australia for his postdoctoral fellowship a few years before, and that’s how he’d come to be focused for so long on this particular phage purification process. His work largely done, he planned to head back to Australia in just a few months. But this was no time to wind down.

  The SDSU lab was state-of-the-art, but it was an experimental facility—they had never prepared anything for human consumption, if you didn’t count the food they brought in for departmental parties. The next morning, everyone in the lab gathered for a roundtable session to plan. Anca joined the tag-team effort to keep every step of the process on as tight a turnaround time as possible.

  The purification protocol they had developed was a process that first concentrated and cleaned the phages, then soaked, chilled, and eventually centrifuged them to separate out the endotoxin, then tested again to be sure the phages were still active. Multiply that by four different phages, a snag in getting a needed test kit overnighted from Germany over the weekend, and additional steps needed to reduce stubborn endotoxins, and everyone was worried that the clock—and Tom’s luck—would run out.

  At each step, the phages checked out: highly active. They performed sterility tests and confirmed that no other microorganisms—bacteria or fungi—were present in the lysates. And finally, the moment of truth: the last-round endotoxin test. They fed the data from the previous steps into a spectrophotometer, which uses light to measure the density of endotoxin particles in the prep, pressed the Read button, and waited for the results to display on the screen. The initial numbers looked good, but were they good enough to use the phages on Tom? The only way to be more certain was to do additional analysis of the raw data and chart it. Thirty minutes later they had their answer.

  They’d measured the endotoxin concentration of the starting phage lysate that the Texas lab had sent. It read 61,965 endotoxin units per milliliter. The FDA required the cleaned lysate to measure less than 1,000 to be safe and maintain a high phage dose. Finally, the cleaned phage results came back: 667 endotoxin units per milliliter. They had reduced the endotoxins by almost a hundredfold in less than twenty-four hours. The team high-fived.

  Tuesday morning, Forest and Anca handed the vials of phages, bubble-wrapped and boxed for the drive, to Dr. Ji Sun in the investigational pharmacy at UCSD’s Thornton Hospital. The phage cocktail was on the last leg of its journey, to the pharmacy and then its final stop: Tom.

  Tom: Interlude VI

  The desert is a vast sea of red sand, scattered with the remnants of invertebrate corpses. Mine will soon be among them. I am walking on a carpet of petrified fossils, flesh, fur, and feces, formed over millennia. My mouth is a dry crevice. The river that is my blood is thick, dancing along the artery, congealing. The transition from organic to inorganic, animate to inanimate, is ephemeral. We simply begin to exist as carbonized matter, as the water that comprises most of our bodies vaporizes. Our elements return to the earth, in a world where there is no more pain or suffering. I long for that world.

  Although I cannot feel my legs, my feet shuffle onward toward an unknown destination. I think of my great-grandfather, who my relatives told me was a Cherokee who walked alone from Oklahoma to Texas along his own Trail of Tears. A profound sense of desolation and despair washes over me, like a gust of ancestral wind. My people are generations of untouchables.

  I face a relentless, sunless sky with blazing heat. Night never falls, so the moonlight cannot guide me. I climb a dune. From this vantage point, I see what appears to be a copse of lush green trees in the distance. An oasis or a mirage? When I close my eyes, figments of my imagination are glass shards piercing my conjunctiva. My mind is a charlatan, playing tricks. The fever sings in mental wires. Do I even attempt to try to reach this alleged sanctuary, and risk having hope crushed by the heel of an unseen boot? Or do I clutch my apparitions like a shroud around me with gnarled hands, holding them as enemies, closer than friends? I long to be a part of civilization. To be human. Not a leper.

  I am struck by the realization that if I am loneliness personified, then I must still be alive. If faith is knowing what I hope for and being certain of what I cannot see, then surely, I am lacking in faith. But I summon what little energy I have left and trudge on; my feet are a lifetime of burning in every moment. As I draw closer, I can see that the trees are genuine, and they are alive. But they are not lush; they are green on top and black with blight on the bottom, from faulty photosynthesis. A small pool of water surrounds them. Every cell in my body cries out for its nourishment. Its inky liquid has a slick, metallic sheen and appears thick, like an oil spill. But I will drink it. I must. I am dying of thirst.

  Before I reach the water, three men materialize. They sit around the pool in lotus position. One is the holy man who presented Steff and me with the leaf. The other two are quiet-voiced elders with skin like bleached coral, as white as their robes, devoid of melanin. Their hair, too, is uniformly long and white. They watch me impassively. They have been expecting me. Just as suddenly, a blowfly appears and lands on the corner of my eye. It has been expecting me, too. In search of salt or a place to lay eggs, it flies into my mouth. I try to swallow it and choke. The sound startles the three men, who begin to talk in a foreign tongue, to each other and then to me. I know at once that they are deciding my fate. They ask me three questions, but I do not understand them.

  The first-met stranger speaks to me in English, but his eyes do not meet mine. “You have not eaten enough of the leaf,” he says admonishingly, “and you did not answer our questions. You must remain here for another seven years.”

  I hear another man’s words, through a tunnel, from far away. “Failure to thrive…,” the hollow voice says.

  The three men rise and leave, their long white robes flowing. At once, the pond transforms into a swirling cloud of blue-black, buzzing blowflies. As the swarm lifts and moves toward me in a black halo, the bones of a ram are revealed, picked clean. Its horns are diabolically twisted, and its open jaw gapes like a reaper. Their last host devoured, one thousand compound eyes are now upon me, their forelegs rubbing together as in prayer before a feast. Their mandibles exude digestive enzymes that will facilitate putrefaction. I want to welcome them to the task, but there are no tools to end my misery. In desperation, I clutch handfuls of sand and swallow them; the grit tears at my pharynx and esophagus. I look down to see sand pouring from my ribs, dripping as if from an hourglass, onto the desert floor. I fall to my knees, throw my head back, and howl, my spirit broken.

  PART IV

  The Darwinian Dance

  Nothing is to be feared, only understood.

  —Marie Curie

  20

  THE BLOOD ORANGE TREE

  March 15, 2016

  The next day, March 15, will remain burned in my memory forever. As I rinsed my coffee cup at the kitchen sink in the quiet light before sunrise, a pair of Bullock’s orioles landed on top of the blood orange tree Tom had planted eight years ago. They were
migrants that wintered in Mexico, flew north to breed in Southern California in the spring, and left by early fall. Tom and I tracked their movements regularly when they took up their annual residence in the palm trees behind our backyard. The male had bright yellow and black plumage that never failed to take our breath away. The female sometimes fed at our hummingbird feeder. This was the first day I had seen them this season. It felt like a sign.

  I arrived at the hospital earlier than usual, around seven, and stepped out of the elevator to see a large group of doctors surrounding Tom’s bed. I immediately panicked and thought the worst. Had Tom died in the night? Then I recognized a few of them; it was the nephrology team. Tom was still alive, but their visit could mean only one thing. They were ready to start dialysis on a second’s notice. The senior nephrologist was a colleague I knew from a research project we had discussed a year ago, Dr. Joe Ix, chief of the nephrology division. After gowning up and entering Bed 11, I stood at Tom’s side.

  Joe looked at me in surprise. “Steffanie! It’s great to see you,” he greeted me warmly at first, but then I saw him blanch when the reality hit him. “But I hope you are here for professional reasons and not a personal one.”

  I put my hand on Tom’s and looked up at my colleague with bloodshot eyes.

  “Hi, Joe. This is my husband.”

  “That’s what I was afraid of,” he said quietly, and put his hand on my shoulder in sympathy. “I am so, so sorry. I can’t imagine what you’re going through.” I knew from his tone that he thought Tom was going to die. By now, I realized, so did most of the docs. “I can see you have already met some of my residents,” Joe continued. “We need you to sign this consent form for kidney dialysis. It could be hours or, at the latest, tomorrow morning, but I’m afraid it’s imminent. We can’t risk not being able to find you when the time comes.”

  I thanked Joe and signed the form with a wavering hand.

  “With any luck, we’ll be starting phage therapy sometime today,” I told him. Joe had heard about our plans and wished me luck. He promised to call me personally when they began dialyzing Tom.

  After the huddle of doctors left, I looked at Tom with newly sobered eyes. This might be one of the last times I would touch his skin while it was still warm. I ran my fingers over his face. Even through my blue gloves, I could feel the newly forming hollows around his eye orbits and under his cheekbones. His nurse had scribbled his weight on the whiteboard; he was now 187 pounds, which looked skeletal on his 6-foot-5-inch frame. He had lost over one hundred pounds.

  Since Tom was feverish, we tried to keep him cool with ice packs under his armpits and a small fan. I had brought in a cooling sports towel that would remain cold for hours; I remembered buying it for him last summer when we had trekked the Virunga Mountains in Rwanda to see the mountain gorillas. A lifetime ago.

  It felt like every random event was happening for a reason, beyond serendipity. Pandora started playing Madeleine Peyroux’s version of a Leonard Cohen classic, “Dance Me to the End of Love.” Tom and I had seen her in concert only a few months before he fell ill. I sang the words to him and closed my eyes, heart aching in their irony, and not caring that I was off-key.

  I laid my head on his chest as close as the snaking tubes would let me, knowing that it was the vent and not his own lungs that were responsible for its rise and fall. The sliding glass door to Bed 11 squeaked, and I turned to see Chip there, looking embarrassed that he was interrupting an intimate moment. I motioned for him to come inside.

  Although Chip was unflappable, I could tell he had news; he was almost pulsating with excitement. “Jeremy just finished the endotoxin assay,” he began. “The level is finally well below what the FDA required for safety.” He waved a piece of paper like a flag. “So we have the eIND, and Jeremy is en route with Forest and Anca, bringing the phage prep back to the pharmacy.”

  I let out a whoop and looked down at Tom. Not even a flicker of movement. Chip added that the Navy had finished their endotoxin purification assay as well and were almost ready to ship their phages to us. And the FDA had made an unprecedented move, he said. In the past, they required that a separate eIND be issued for each drug—or in this case, each phage—but they had conferred and decided that an eIND could be issued for each phage cocktail. It sounds so simple, but it was a huge step in streamlining the process.

  “At least we won’t die from the papercuts incurred in the FDA’s administrative bureaucracy,” Chip quipped. “All joking aside, they have been incredibly helpful, and they are deeply interested in the outcome of Tom’s case.”

  I was glad to hear that and explained to Chip what Joe Ix had just shared: kidney dialysis was imminent.

  “Yes, I could see that’s where things were headed,” Chip replied. “But we can start phage therapy as soon as the pharmacy gets the phage cocktail titrated and prepares the buffer,” he assured me.

  Good news, at last. Mix, stir, and send upstairs to Tom—finally!

  “So, if you’re in agreement, the plan is to administer the Texas phages directly into the drains in Tom’s abdominal cavity to reach those abscessed pockets,” Chip explained. The drains would then be closed temporarily, trapping the phages and A. baumannii together so the phages could do their work.

  “But I wanted to talk to you about the Navy phages, which are more potent. Carl advised that since Tom is now fully colonized with Acinetobacter, we should administer those phages intravenously.”

  Chip looked at me to gauge whether I understood the significance of his question. I did.

  “I was afraid you were going to say that,” I replied, with a huge sigh. “Ry warned that since his bacteria are multiplying every thirty minutes, any that are resistant will multiply and take over. So, if we’re too conservative and only inject phage into his abdominal cavities, then we could miss reservoirs of bacteria that the drains can’t reach.”

  “Precisely,” Chip said, impressed, or maybe just relieved, that I was up to speed. “Of course, with IV phage administration we greatly increase the risk of septic shock. But if we start with intracavity administration and Tom tolerates it, then I feel confident about moving to IV administration as phase two. The benefits are worth the risk.”

  I didn’t have to think twice. This was the best chance to save Tom. And if he died? Well, this would be the first case of IV phage therapy to treat a systemic superbug infection in the US. We would still have gotten important information that could help others, and he’d made it clear how important that was to him. If he were able, I knew he’d insist on it. No retreat.

  “Let’s go for it. We didn’t come this far to hold back now.”

  Chip nodded. I got the impression that he had thought it was going to be a lot more difficult to convince me.

  In the spirit of the day, I presented Chip with a little gift bag. He looked at me in surprise, and pulled out a little box of chocolates that I had regifted from a former student who was now based in Kentucky.

  “Look closely at the box,” I told him with a smirk.

  “Bourbon balls!” he cried, and let out a chuckle.

  “Yes, indeed, my Alabama friend,” I told him. “Clearly you have a pair.”

  With Tom’s kidneys now beginning to fail, his nurse, Chris, was recording his urine output on an hourly basis. I watched every drip of urine flow from his catheter into a plastic, flask-shaped bag, knowing that the moment it dipped below the threshold, the nephrology team would descend like a cloud of flies to start dialysis. The magic number was 30 milliliters per hour. If Tom made less, it meant his kidneys were functioning at less than 15 percent.

  Every once in a while, Tom would grimace, his eyebrows would furrow, or he’d flail his hands in the air when he wasn’t restrained, reacting to some invisible threat only he could see. Otherwise, he lay immobile. Comatose.

  The wait for the cocktails to come up from the pharmacy was excruciating. Every clock in sight seemed frozen in time, as they had been in Luxor, waiting for the airlift out. Th
e purified phages had been delivered to the investigational pharmacy hours ago, and I’d just assumed they’d be measured out into doses and be up shortly, but that wasn’t happening. Was there yet another snag? I tried focusing on Tom and on practical details and always the music.

  I swayed my hips to the endless music loops playing on Pandora, which was now Creedence Clearwater Revival’s “Have You Ever Seen the Rain,” and lifted the catheter tubing to usher the newly formed drops of urine into the bag. The color wasn’t liquid gold, but a dark orangey-red, like a leftover jack-o’-lantern. I’d have to remember to razz Tom about this and give him the fascinating lecture on how to “read” the chemical composition of urine—the quantity, clarity, color, hue, fizz, and foam—for signs of kidney function and liver ailments, as well as inflammations, infections, diabetes, heart disease, and certain medication issues.

  Admittedly, those signs weren’t looking good for him just now, given the cloudy, darkening color palette of late and the Halloween hue in his catheter, but they were just barely good enough to hold off dialysis and hold on to the hope that the phages might change things for the better. Kidney failure is so critical to avoid because as they falter, waste products build up in the blood, the body’s electrolyte balance goes off kilter, and organs start to die off, including the brain.