The Perfect Predator

by Steffanie Strathdee

  “Forty mils this hour,” I reported dutifully to Chris in a soft voice, as he entered Tom’s vitals into the computer. Blood pressure: 90/55, and that was supported by three pressors. Heart rate: 133, still tachy. Respiration rate: 29, despite maximum vent settings. And his latest creatinine level—the best measure of his kidney function—was 3.9. That meant he was deteriorating from AKI—acute kidney injury—to full-out kidney failure. So, heart, lungs, and kidneys were all on the verge of collapse. That was how the man in Bed 9 had died; one moment, it was a bad case of the flu, the next, his heart gave out.

  Boom. Just like that.

  Since epidemiologists like me crunch numbers for a living, I usually take solace in statistics. But of the 4 million admissions to ICUs across the United States each year, up to one in five patients die. I was praying that Tom wouldn’t be one of them. He had been back in the TICU for nearly two months, way longer than the three-day average, and this was his second time there. Although they rotated in shifts, by now the girls and I knew the names of most of the nurses and doctors, physical therapists, lift team, and housekeeping staff. And they knew ours. We were family of sorts now, comfortable enough to be candid, candid enough to be irritating. Me, especially, with my habit of hyperfocus and constant questions. Sometimes, I’d hear myself pressuring for answers no one had, but I couldn’t stop.

  I looked at my watch. Mid-afternoon. Just when I was getting ready to rattle a cage or two, Chip appeared at the doorway to Tom’s room, Bed 11. His role as the protocol chair for Tom’s phage therapy meant that he was the point person for the entire operation. I rarely saw him without a smile. Today, the freckles stood out more prominently on his pale cheeks. He was nervous.

  “Chip, what in God’s name is taking the pharmacists so long?” I whined, wringing my hands.

  “I know, the wait is gut-wrenching for me, too,” Chip admitted. “But the research pharmacy is used to preparing medications for clinical trials, not viruses. Think about it: this is the likes of which they have never seen. And they not only need to get the dilutions right, but each bag of phage prep needs to be dispensed with the right volume—a billion phages per dose—then labeled with its contents and the eIND number. The techs also need to make up a buffer solution so that the phages enter an environment with a neutral pH. And we need enough to dose him every two hours, at least for now.”

  Okay. I remembered this from my reading and Ry’s phone lecture. Since we would be injecting the Texas phage prep into the drains in Tom’s abdominal cavity, the phages could face an acidic pH from the bile, ascites, and stomach acid, so a buffer solution of water and sodium bicarbonate was being prepared to neutralize their surroundings. Got acid? Get a base, and mix them to neutralize it. High school chemistry. Alka-Seltzer without the plop and the fizz.

  Suddenly I realized that there was a key detail to the protocol that I had overlooked. “How did you decide what concentration of phage to have the pharmacy prepare?” I asked Chip quickly, while I combed the library in my mind. I couldn’t remember reading a single article that advised on this topic. Chip fidgeted with a piece of paper that he took out of an envelope as he thought about how to respond. He was in a tough spot. I was not just his friend and colleague, but the wife of his patient, Patient Zero in an unprecedented experiment that the whole phage community, Navy research lab, and FDA was watching. Nah, no pressure.

  “Carl and Maia were very helpful,” Chip replied. “But basically, no one knows the ideal concentration of phages to optimize their killing potential while minimizing the chance of septic shock. And when it comes to IV phage administration, it’s been done in animal models, but there are no documented cases in the literature. That is, in humans.”

  Chip looked up from the paper he now held in his hand, and his eyes met mine with an even gaze. “We’re using standard IV dosing measures that take into account Tom’s weight and the endotoxin level, as well as the potency of the phage cocktail. So, we can estimate pretty closely how much phage we are injecting into Tom’s drains or his bloodstream. But the phages will multiply to an unknown extent. It’s a double-edged sword; we want them to multiply to eradicate the Acinetobacter, but we can’t anticipate exactly what they will do once they are inside him. It would be easy to think about it as warfare, in which each side takes on new weapons, but in reality, it is survival of the fittest. There’s a complex interplay between the phages’ antibacterial activity, Tom’s immune system, and how quickly the surviving bacteria take the lead and proliferate. We just don’t know enough to predict how that will play out. To be perfectly honest, we are flying by the seat of our pants here.”

  I stood there nodding, but felt numb inside. This was a classic catch-22. Do nothing, he dies. Do something, he might die anyway.

  Fuck.

  “So, you are saying that it’s a guess?” I asked Chip, looking him directly in the eye. It was Sir Isaac Newton who reputedly said, “No great discovery was ever made without a bold guess.” We were about to test his hypothesis. I remembered that the doctors who treated Anne Miller, the first person to be treated with penicillin in the US, had not known what dose to use either. No, I am not alone.

  Chip took a deep breath and thrust the paper he was holding toward me. “I need you to review the informed consent form for the phage therapy. Let me know if you have any concerns or questions, and if you agree, sign it,” he said.

  Consent to Emergently Administer Bacteriophages

  in the Treatment of Multi-Drug-Resistant

  Acinetobacter baumannii Infection

  I understand that my husband has a life-threatening infection with a multi-drug-resistant Acinetobacter baumannii strain or strains and that, despite efforts to treat the infection with antibiotics and drainage, he remains critically ill.

  I have expressed an interest in exploring whether experimental treatment of his infection with bacteriophages can be directed at my husband’s organism. I understand that bacteriophages are best described as “viruses that attack bacteria” and that there has been some experience treating human and animal infections with these organisms under experimental conditions but that these agents are not approved for clinical use in the United States or Western Europe. I understand that physicians and scientists at UCSD, Texas A&M University, AmpliPhi, and other research laboratories have collaborated to identify phages that have activity against my husband’s organism in laboratory-based studies. I understand that although great care was made to perform these studies and to prepare phages that might be used to treat my husband as safely as possible, these efforts have been done under a very short time frame using approaches and laboratory reagents that are used for research studies, but some of these approaches and reagents are not ones that would be used for the preparation of clinically used medicines. Thus, the laboratories, biotechnology companies, physicians, or scientists who have participated in this effort cannot provide assurances about either benefits from or the safety of the approach.

  The potential benefits and side effects of bacteriophage therapy for bacterial infections have not been extensively studied in human clinical trials. Although it is possible that these bacteriophages will decrease the amount of Acinetobacter baumannii in my husband’s abdomen or other areas, there are no assurances that this will happen. Because of the limited experience using bacteriophages to treat bacterial infections in man, all of the potential side effects of this study cannot be predicted at this time. It is possible that administration of these materials could result in a worsening of his condition or even his death. It is possible that my husband could have an adverse reaction to the bacteriophages or to other substances (including bacterial endotoxin or other substances) that might be present in the material. These side effects could include a reduction in blood pressure, changes in his heart rate, and/or damages to organs including (but not limited to) the lungs, liver, and kidneys.

  If these bacteriophages are used in an effort to treat my husband’s infection, I understand that one or more of the b
acteriophages that have been demonstrated to have activity against my husband’s organism in the laboratory will be administered through catheters that have been previously placed in an effort to drain tissue collections of the Acinetobacter within my husband’s abdomen. Depending on his condition and his tolerance of the instillation of the bacteriophages into the abscess cavities, I understand that one or more of the bacteriophages might also be given by intravenous, intraperitoneal, or oral routes.

  I understand that those caring for my husband will closely follow his clinical condition during and after the bacteriophage administration and that they will perform laboratory studies designed to determine whether the bacteriophages have decreased the amount or changed the nature of the Acinetobacter baumannii (or other bacteria) that are cultured from my husband. These studies will include studies performed in the UCSD Medical Center Clinical Microbiology Laboratory but may also include specialized studies performed in research laboratories at UCSD, Texas A&M, or other research entities.

  I have been provided with a copy of this form and given an opportunity to ask any questions that I might have. I have been told that I can ask additional questions at any time and that I can reach Drs. Schooley or Taplitz through the UCSD Medical Center or on their cellular telephones. I understand that the bacteriophages are being administered under an emergency, single-patient Investigational New Drug Application [Individual Patient, Emergency 21 CFR 312.310(d)] issued by the US Food and Drug Administration and that, as per FDA guidance, the UCSD Human Research Protections Program will be notified of this intervention after the fact.

  Understanding that my husband’s clinical condition is grave and that there is a substantial chance of morbidity and mortality with or without the experimental use of these bacteriophages, I consent to their administration on behalf of my husband, who is not currently sufficiently alert and oriented to provide consent for himself. I understand that the alternative to proceeding with this research study is to continue medical therapy according to clinical judgment and recommendations of my husband’s treatment team. I understand that I can withdraw my consent at any time for any reason and that a decision about whether to proceed with bacteriophage therapy or to terminate bacteriophage therapy will not prejudice my husband’s care by his medical care team in any way.

  Steffanie Strathdee, PhD Date

  On behalf of Thomas Patterson, PhD

  Witness Date

  As I read the consent form over, my stomach did a somersault. I had seen an earlier version of this form a few days ago when Chip was preparing the necessary documents to obtain FDA approval for the phage therapy, so the contents shouldn’t have come as a surprise. But at the time, the Scientist-Me had read it. This time, I was reading it as Wife-Me, signing it on his behalf as his power of attorney.

  A new reality was setting in. If Tom died of septic shock now, it would be because this was a treatment that I had sought out and initiated, albeit with the help of Chip and others. What if I killed him? How could his daughters ever forgive me? How could I ever forgive myself? The immense responsibility of this dilemma was suffocating. Surreal. Just three months earlier, Tom and I had been exploring a pyramid, having the time of our lives. Now he was in a coma and we were about to inject viruses into his body to save his life from a superbug. I can’t believe this is our life, I thought miserably. Tom always said that we had horseshoes up our butt. We sure as hell needed them today, along with some phages that could swim upstream.

  As I signed the form and handed it back to Chip, my eyes were gleaming with a combination of tears, fear, and hope. “I don’t know why, or how to explain it,” I said forcefully, “but I think this is going to work.” There was absolutely no concrete evidence for me to think this way. Call it instinct, a gut feeling, or a spidey-sense that had rubbed off from my sessions with Robert, who remained convinced that it wasn’t Tom’s time.

  “I do, too,” said Chip, with a tight smile. “I do, too.”

  I remembered what the scientist and Nobel Prize winner Barbara McClintock had said in 1983 after receiving the award for her discovery of genetic transposition, which showed that genes could “jump” and switch the physical characteristics of cells on and off. She had done most of her research in the 1940s and ’50s, but had been on the margins of the scientific community for decades. She was brilliant and she trusted her instincts. “If you know you are on the right track, if you have this inner knowledge, then nobody can turn you off… no matter what they say.” Hell, yeah, sister.

  We didn’t have the luxury of time for debate any longer anyway. Carly had mentioned that one of the medical residents had pulled her aside the day before and said, “If something doesn’t work soon, we’re going to have to start unplugging things.” We’d been ever hopeful, but the truth was that Tom would die if we didn’t do something drastic. We had nothing to lose.

  Chip left for a while to check on his other patients, and I watched Chris empty the ostomy bags attached to the five drains in Tom’s abdomen. These were filling up every few hours with a thick, cloudy, purulent liquid that ranged in color from yellowish to brownish; a mixture of pus, ascites fluid, bile, and god knows what. There are no medical terms that describe its smell: like a swamp. I knew from the last round of bacterial cultures that the ooze from at least three of these orifices was teeming with Acinetobacter, which had crowded out most of his normal gut flora.

  “Hey, don’t throw all that out,” I called over to Chris as he emptied the bags. “We need some for the baseline samples.” He raised his eyebrows at me and wrinkled his nose, as if to say, Seriously? Shouldn’t you be focused on what might be the last few hours you have with your husband? But Chris was calm, professional, and polite enough not to say this out loud. Or maybe he wasn’t thinking that at all, and it was my own inner voice, scolding and not at all polite.

  I cleared my throat and explained my rationale. “I know it seems crazy, but aside from being husband and wife, at our core, Tom and I are both scientists.” I stopped and took a deep, shaky breath, realizing that I was also justifying my detached demeanor to that other part of myself. “Even if Tom dies, we need to learn something from the phage treatment. And if it works, we need to document it as carefully as possible so it can ultimately help others. If we forgot to do this and Tom were conscious, his dying words would be: ‘What do you mean, you forgot the baseline sample? What kind of researcher are you?’” I laughed, and it sounded a little hysterical. “So please, no matter what, save everything you can.”

  Chris nodded. He’d been an ICU nurse for a while, and although this was probably not something most people brought up in moments like these with their loved ones, he knew this case was being documented as medical research, and as such, data collection had to be just so.

  At some point, as the afternoon wore on and predictions about when the phages would arrive grew later, it was clear that my constant calls and texts to everyone for updates weren’t actually helping Tom or anyone else. I was only adding to the burden for those who were meticulously monitoring Tom and, in the pharmacy, carefully diluting the phage cocktail to prepare them for injection.

  Tom, however, was a captive audience, so I just kept nattering to him about every possible thing—phages, orioles, Newton, and the kittens—as if my talking to him kept him grounded in this world. With me. If Tom could hear me through the coma he was probably ready to jump out of his skin just to escape. I could see myself, from outside myself, in this manic mode, and I saw a desperate woman, but I couldn’t get her to calm down.

  Just then, I saw a familiar figure with a red bobbed hairdo make its way down the hallway pulling a rolling suitcase. My friend Michelle from Vancouver was a flight attendant and had managed to snag the last vacant seat on the daily nonstop flight so that she could come and rescue me. By the look on her face as she peered into Bed 11, I needed it as much as Tom.

  “Hey, girlfriend,” Michelle began, looking past me at Tom. I could tell she was shocked.

  “D
on’t come in without gloves and a gown!” I snapped at her, stunned at how harsh my voice sounded. I hadn’t even said hello.

  “Whoa,” she replied, putting her hands up in defense. She pulled a yellow gown over her head and snapped on blue gloves. “Sounds like you need some R&R, big time.”

  My eyes filled with tears for what must have been the millionth time.

  “I’m so sorry,” I told her, shaking my head in disgust at myself. Like everyone around me, she was doing the best she could to help. I caught Michelle up on the plan for the day, and the long delays we had faced.

  She crept closer to Tom and patted his hand. “Hey, Tom,” she said. “It’s Michelle, if you can hear me…”

  She turned to me. “I wouldn’t even recognize him,” she said. “He looks, he looks…” She didn’t finish her sentence, but we’d known each other for twenty years, watched each other raise kids, and had had our share of laughter and tears together. Like a corpse, her face said. She turned back to me.

  “When did you eat last?” she asked.

  I had to think about it. “I had a banana on the drive in this morning.”

  Marilyn came up behind me, standing at the doorway, and introduced herself to Michelle. “I’ve got an idea,” she said brightly. “How about Michelle and you take off and have some time for yourselves. Carly and Frances are both due in this afternoon, right? If it looks like the phage therapy is going to happen, one of us will call you and you can come back.”

  Marilyn looked at me expectantly. Her haircut and calm demeanor reminded us both of our friend Heather back in Vancouver. I looked at Michelle, then at Tom, then slowly nodded. She was right. I was doing no one any good at the moment. Frances would be here any minute for her afternoon shift. Carly, too. Tom wouldn’t be alone. And I needed to summon my own kind of mindfulness if I was going to get through the next few days.