Suddenly, Tom opened his eyes and looked at me solemnly. Back on the vent now, with a wide breathing tube directly attached to his trachea, he could no longer speak. But he didn’t have to. I knew what he was thinking as I gripped his hand, and together we listened to the Eagles’ last cryptic verse. The sense that Tom could “check out” any time but might never leave this place hit entirely too close to home.
Tom: Interlude IV
I am in a terrifying world that no one else can see.
And I am untouchable.
A sign says: INFECTIOUS AGENT.
I am the pariah.
PART III
The Perfect Predator
When you have exhausted all possibilities, remember this: you haven’t.
—Attributed to Thomas Edison
14
THE SPIDER TO CATCH THE FLY
February 16–20, 2016
Throughout Tom’s illness, Davey had encouraged me to call day or night, explained medicalese to me in layman’s terms, and didn’t sugarcoat the truth. Ever. And I needed a reality check. If I’d been protecting myself from some truth about Tom’s situation, then the recent sobering conference call with my colleagues on retreat had ripped off the Band-Aid. I texted Davey and we met for lunch the next day.
I told him about the conference call and how, after I’d described Tom’s situation in some detail, they’d gone unusually quiet, then sympathetic before saying our goodbyes. And how in that moment when they thought I’d hung up, but I hadn’t quite, I’d overheard the former university chancellor’s comment to those around the table, the question I wasn’t supposed to hear.
“Has anyone told Steff that her husband is going to die?”
You might think that two and a half months with Tom at death’s door would have left me with no doubt that he was dying. But my experience was also that he’d been “dying” for two and a half months—and hadn’t died. He’d just kept pulling through over and over again, hanging in there like the Energizer Bunny, just going and going and going, waiting for somebody to come up with the right antibiotic.
“Give it to me straight,” I told Davey, telling myself to hold it together as I shoveled a forkful of quinoa salad into my mouth. “Tom is dying. He is slowly slipping away. Am I right?”
Davey sipped some Diet Coke and rubbed his day-old peach fuzz. He was thinking how to respond to me truthfully as he toyed with his straw.
“I think so, yes,” he said slowly. “Although he is not in multisystem organ failure. He is on the vent, so his lungs are failing, and he is on pressors to keep his blood pressure up, but while his kidneys have taken a hit, he doesn’t need dialysis.” Davey’s voice sounded professional, but his eyes fluttered a little too rapidly. I knew he was blinking back tears, being brave. For my sake.
“Doesn’t need dialysis—yet?” I asked him, inwardly pleading that he would say, “No, never. Tom’s kidneys will not fail.” He did not say this. His silence and sad eyes said otherwise.
It was a helluva way to celebrate Tom’s birthday on February 18, but we gave it our best shot. My mom and dad flew in from Toronto, and they busied themselves tying balloons to the rails of his bed. Tom was on the trach vent, so he couldn’t talk, but he opened his eyes from time to time. It seemed possible that he was at least semiconscious in that haze, and when I saw his gaze land on a balloon, I took that as a cue.
“Happy birthday, honey! You are sixty-nine today!” I held my laptop in front of him and clicked on a video of our departmental staff and students singing “Happy Birthday” and clapping. We sang along. Tom’s gaze shifted and he stared at the ceiling. If he could have had a cake and candles, I know what his birthday wish would have been: Get me home. We all had the same wish. I couldn’t imagine what he was thinking—might be thinking, or hallucinating, for that matter—but if in some rational corner of his brain he was doing the math, he’d realize that he’d spent almost three months in the hospital and there was no sign of him getting better.
On the chair, there was a gift bag waiting, with our names handwritten on a small accompanying envelope. Inside was a card with a hand-painted rainbow and handwritten note with a delicate flourish: “To the most inspirational couple we know, who has taught both of us what true love is really about. Love ML and Yash.” Tom and I had had to miss the wedding of our postdoctoral fellow, Maria Luisa, whom we affectionately called ML, but despite all they had going on, they’d sent this along. In the bag were two white T-shirts, one large and one 2XL. Both shirts had a magnified photo depicting chains of short bacterial rods, with the words I SURVIVED IRAQIBACTER! emblazoned on it. I laughed with delight, draped Tom’s T-shirt across his chest, and snapped a photo with my cell phone. He was far from being 2XL anymore, but at least the survival message was encouraging.
“Honey,” I whispered in his ear. “You aren’t going to win any fashion shows with this, but let’s hope that this is the ‘before’ photo, and in the ‘after’ one, you will be wearing this instead of your hospital gown the day we get you the hell out of here.”
Tom didn’t stir. His eyes had closed.
Party over, balloons gone from Tom’s bed rails, the room sank back to pallid gray tones. The color of hopelessness. It wasn’t like Tom to give up, but how much longer could he hold on? How much fight could he possibly have left? I pulled up a chair and sat and stroked his cheek. He closed his eyes. The Beatles song “While My Guitar Gently Weeps” drifted from the Pandora station. It had always been one of our favorites.
“Have I told you today how much I love you?” I said softly to him, and I saw his head move, just barely.
I wasn’t sure, as I climbed into my Prius to head home, how much fight I had left in me, either. I propped my phone in the dashboard cradle for a drive-time chat with my sister Jill in Toronto. Three years younger than me, Jill had always been a glass-half-full kind of person. Now an elementary school teacher, she brought her trademark equanimity each day to a crowded class of fifth graders—and lately to me. She did yoga and meditated, and had developed a new sense of calm—mindfulness before it was trendy—that I admired, especially since I’d never been one to sit still long enough to get mindful. She had always looked up to me, though, for being kind of fearless, or at least that’s how it looked to her. It had been hard to show her how vulnerable I felt some days. Today was one of them, and I was too spent to pretend otherwise.
“We’re up against the wall, Jill—no treatment options left—and I’m just so, so tired.” I had to wipe my eyes to see the road. “I’m not even the sick one, and I’m about to crack.”
She listened patiently as I relayed the details of the day and the crushing helplessness that was overwhelming me. In my mind’s eye, I pictured her sitting in lotus position on her couch, twirling a lock of her blond hair, like she always did.
“It must be so hard, Steff, and I can see why you’d feel that way,” she said. “But think of the worst things that have ever happened to you. You made it through then, and you can make it through this.”
She knew better than anyone. She knew my history of being a bullied kid—the nerdy girl who didn’t know how to play dumb. I had even been lit on fire one day as a prank. I was about ten and walking home from school one winter day in my favorite shearling parka, when a bunch of boys ran up and dropped something into my hood, and ran off, laughing. The girl I was walking with screamed, “You’re on fire!” I didn’t even realize it until she screamed again. Instead of panicking, I dropped to the ground and rolled in the snow, then shook off my coat before it could burn my skin.
“And do you remember what you said when everyone asked you how you knew to drop and roll? You said, ‘I don’t know; I just did what I had to do.’ That’s who you are, Steff. That’s what you do.”
By the end of our conversation, I felt the old sense of fearlessness rising. That Little-Girl Me had her long blond hair burned off but still walked the rest of the way home for lunch. And as hard as life was now, I still remembered the night
Tom proposed like it was yesterday, and the bioluminescent tide. The glow looks so light and otherworldly, but it’s the stress of crashing in the surf that activates the phytoplankton’s bioluminescence.
I knew that feeling. The stress of crashing, anyway. Now I just needed to get my glow on.
“I guess it’s time to put on my big-girl pants,” I told Jill. “Game on. This bug has messed with the wrong epidemiologist.”
Home to the kitties and the mail. Then an early shower, exhausted. A glass of wine. Okay, two. But I couldn’t stop hearing that conference call question: “Has anyone told Steff that her husband is going to die?” Well, they have now. But how to tell if someone is really dying? I thought back to the late 1980s, when I had volunteered at Casey House hospice in Toronto. I remember reading some of the brochures that the staff shared with families to prepare them for the death of their loved one. Extreme weight loss and muscle wasting. Check. Sleeping most of the time. Check. Loss of cognition. I thought of Tom’s continuing delusions and mental deterioration. Big time.
But I’d grown accustomed to the internal debate, the one in my own mind, between the hyperrational Scientist-Me, the problem-solving Pit Bull, and the Wife-Me, anxious and hoping for a miracle—someone or something that would show up just in the nick of time and save Tom. Maybe I was in denial. Maybe I did need to wake up and accept what was obvious to everyone else. To anyone with a rational grasp of the facts. I thought of my PhD adviser, Dr. Randy Coates, a medical doctor turned epidemiologist who had died at age forty-two. The night before I defended my doctoral dissertation, I had a dream where Randy was quizzing me relentlessly on the phone, even though he had died two years earlier. Each question that he asked in my dream was one I received the next day from my thesis committee; I remember smiling ear to ear and answering each one with a new confidence. I passed with glowing reviews. That was just a dream, of course. But what would Randy say if he was here with me now? You’re stuck on the wrong question. The operative question isn’t whether you know that he’s dying. It’s “How do you save this man’s life?” Who cares if you’re not a doctor! You’re a scientist, for god’s sake—think like one!
Okay, then. Ordinarily, if I were designing a research study, I’d identify the problem to be solved, research the existing literature, track down the top experts in the field, pull together a team, and tackle this together. I’m an epidemiologist involved in global health research—that’s what I do every single day. So, what’s stopping me now? I didn’t have the answers—nobody did. But I sure knew how to look. And even if looking was all I could do, it was somewhere to start.
Dressed for work—bathrobe and cat leg-warmers for the night shift—I spent the next few hours on the internet, desperately looking for answers. I had no idea what I was looking for, but I had to start somewhere. I entered the search terms “multidrug resistance,” “Acinetobacter baumannii,” and “alternative therapies” into PubMed. There was the 2010 article I’d seen earlier referring to the “significant challenges” that antibiotic-resistant A. baumannii presents. The conclusion hadn’t been promising, either. Despite the prevalence of Acinetobacter infections and the interest in finding effective treatment, there was a dearth of data providing evidence-based options for treatment.
I continued to search, though, and within the hour, I found an article from 2013, published in the journal Trends in Microbiology. It was titled “Emerging Therapies for Multidrug Resistant Acinetobacter baumannii.” The abstract mentioned several alternatives to traditional antibiotics that had activity against A. baumannii: phage therapy, iron chelation therapy, antimicrobial peptides, prophylactic vaccination, photodynamic therapy, and nitric oxide–based therapies.
In all the conversations and medical literature about antibiotic resistance that had come up since Tom had fallen ill, I’d never heard the docs talk about any of these. I downloaded a PDF of the paper for a closer read and saved it in a folder on my laptop called “Unconventional Cures for TLP”—Tom’s initials.
One by one, I looked up these approaches. A quick lit search determined that iron chelation therapy and antimicrobial peptides had only been studied in vitro, which means in the lab, and neither had yet been clinically tested in vivo, in a living organism. Vaccination was years away, and photodynamic therapy and nitric oxide–based therapies could only be used topically, on the skin. That left only one treatment, phage therapy—now that was interesting. This was the treatment of bacterial infections with bacteriophages, viruses that attack bacteria instead of people.
I sat back on the couch, absently petting Bonita, one of the kittens, who lay on my lap. I closed my eyes, recalling what I had learned in my university microbiology courses back in the mid-eighties. Bacteria are considered the smallest living things on earth, single-celled microorganisms that average about 1,000 nanometers long, or about 0.01—one one-hundredth—the thickness of a single sheet of paper. They are incredibly adaptable and have been found everywhere from inside rocks beneath the ocean floor to volcanic vents. Depending on the species, they can thrive on their own or inside other organisms (as they do in us), sometimes attacking and sometimes coexisting peacefully with their host. They “eat” by metabolizing nutrients in their environment and reproduce by dividing themselves in two. Not sexy, but very efficient.
Phages, on the other hand, are viruses and as a group are notoriously misunderstood, underappreciated, and often maligned, even in the world of science. It’s easy for that to happen when the headlines everyone sees are all about the killer viruses—HIV, Ebola, smallpox, influenza, for instance—or pesky common cold viruses. But there are an estimated 380 trillion viruses in our body, making up our virome. These include billions of peacekeepers, phages that quietly go about their work munching on bacteria, maintaining the balance of power among the ranks of organisms in our various microbiomes. Also, because viruses are so small, one-hundredth the size of a bacteria, scientists couldn’t even see them with light microscopes. And what humans can’t see, they have a hard time conceiving of, much less understanding. What earlier lab scientists could see, however, was that their Petri dishes containing thriving bacterial colonies were sometimes ruined by the sudden appearance of clear spots and streaks. Something was killing them off.
I’d seen that myself in virology class, only by the 1980s we knew what we were looking at, even though we couldn’t see phages with a light microscope. In a lab assignment, we streaked a bacterial culture onto Petri dishes overlaid with agar, that seaweed-based gel mixed with chicken broth. After the bacteria fed on this solidified agar and multiplied into visible polka-dotted colonies a few days later, we pipetted drops of sewage samples onto the dish, labeled them carefully, and incubated them at body temperature. Within another day or two, some of the Petri dishes looked like Swiss cheese; the holes in the agar were plaques—evidence that phages had been hard at work destroying bacteria. Our professor, Dr. Mounir AbouHaidar, inserted the tip of his pipette into a plaque where the phages had attacked the bacteria. Here, he explained, the phage plaques could now be plucked out and added to a flask with billions more of the same target bacteria in warm broth, where the phages would multiply into billions within a few hours. One phage researcher called them “nature’s ninjas.”
The word phage comes from the Greek term phageîn, meaning to eat or devour. Bacteriophages are a specific kind of virus that “eat” bacteria by injecting their DNA into them and turning them into phage manufacturing plants. In the process, they destroy bacteria from the inside and cause it to “lyse” (break open), releasing up to hundreds of new phages called virions. Thus, technically, phages don’t really ever eat in a conventional sense, nor do they reproduce sexually or in any of the creative ways that bacteria, yeast, or other living organisms do. But they do multiply, and with an astonishing efficiency that puts bacteria to shame—or more accurately, to death.
Phages come in many varieties, but thus far, perhaps the most-viewed and best-documented, or scientifically “characterized,�
�� phages are the T4-related coliphages (they attack E. coli), which look like tiny alien spaceships with long spindly legs, not unlike the Star Wars Imperial walkers Cameron used to make from Legos. As with many viruses, the “head” of most phages is a protein shell called a capsid, which sits atop the tail and spindly legs, structures that are unique to phages and come in a variety of shapes and sizes. The capsid is usually the shape of an icosahedron, a twenty-sided structure that resembles a geodesic dome—like Walt Disney World’s EPCOT Center.
Most phages have hollow, short or long tails that they use to latch on to the host bacteria’s cell wall and, like a syringe, inject their genetic material inside. Technically, all of these terms—head, legs, tail—are the language we use because it’s easy and familiar, a human-friendly way to describe them. But the vital active core of their being isn’t in those exterior features we associate with living things at all. Those external features are just a means of transportation—a disposable nano-size space shuttle for the ribbons of genetic material that ride inside the capsid.
Depending on the genetic makeup of a phage, however, some so-called temperate phages invade a bacterial cell and then have the option to ride quietly along, basically snoozing as they integrate their genetic material into their bacterial host’s, until the time comes when an encoded trigger rouses them and they shift into ninja mode. This could be hours or eons. If you’re hoping to wipe out a bacterial infection quickly, you want the lytic kind that goes from zero to phage-rage fast.
I had no idea that phages could be used to treat bacterial infections in people, but the idea was brilliant. I read more, hungrily. Where could I find a doctor who could carry out phage therapy? My hopes were dashed within minutes, because I turned up zip. Although the Environmental Protection Agency had approved a phage preparation as a pesticide to treat tomato rot in 2002, and in 2006 the Food and Drug Administration had approved a phage cocktail for the food industry to disinfect meat and poultry of Listeria bacteria before selling it to consumers, they had yet to approve phages as a treatment for human bacterial infections. I found an article about a research trial in Europe that was using phages to treat burn victims, but the NIH’s clinical trials website didn’t indicate that there were any ongoing trials anywhere in the US. My online search found no phage treatment protocols that we could apply to Tom’s Acinetobacter.
The Perfect Predator Page 14
