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The Perfect Predator

Page 31

by Steffanie Strathdee


  In one sense, Tom’s case was a singular one. But in truth, what happened to Tom could happen to anyone who acquires a multi-drug-resistant bacterial infection, and the chances of that are rising. We can’t afford to be blindsided. Bacteria are evolving much faster than our ability to develop new antibiotics. Even if new antibiotics are found and phage therapy is found to be efficacious and brought to scale, it’s naïve to think that we can simply treat ourselves out of the superbug crisis. We need to be proactive, not reactive.

  What we did to save Tom was a collective effort, drawing from expertise past and present, and from corners of the world that have been overlooked. The “not alone” experience I’d first felt when phage researchers came to Tom’s rescue and when family and friends helped us keep our hope alive—that energy and love came full circle as we faced forward now. With it, came the sense of “something larger” at work, not only at a personal level, but globally.

  I keep thinking of the image of embers burning in a fire. So many times over the past hundred years, people have tried to light the fire under phage therapy, and the sparks went out. But this time, one little ember lit the flame. We don’t know whether phage therapy will be shown efficacious in clinical trials, but it deserves rigorous evaluation. At the very least, if it can render some failing antibiotics useful again, that in and of itself is a game changer. Our work ahead is to get clinical trials of phage therapy underway, all the while helping other compassionate use cases. We may not have the conclusive evidence yet, but we do have precisely what is needed to carry the work forward. We now have evidence-based hope.

  EPILOGUE

  July 2020

  There is always hope in life, because there is always hope in science.

  —Françoise Barré-Sinoussi

  Tom and I returned to work in April 2017, exactly a year after he was taken off life support. It’s been anything but business as usual. Tom’s recovery was multifaceted and included both physical and psychological healing. He had short-term memory problems at first—struggling to find a word, for example—but that cleared up. He still suffers from persistent numbness in his feet, possibly due to the gorilla-cillins he took or his worsening diabetes, since the infection destroyed one-third of his pancreas. After so many episodes of septic shock, his heart had taken a beating, so he was put on a fistful of prescription meds for mild congestive heart failure. He has trouble putting on weight, too. We could manage all that, but about four months after leaving the hospital, it was clear that Tom’s PTSD wasn’t going to go away on its own.

  For months I was struggling, too. Instead of flashbacks to hallucinations, I seemed to have some kind of phantom limb syndrome, feeling the tug of emotions that were part of the nightmare we’d all endured—and supposedly moved past. The illness was over, but my reactions to it were not. I would overreact to the smallest hiccup. When Tom fell and skinned his knee, barfed up his breakfast, or once when I waited too long for a taxi, I went into full panic mode, adrenaline pumping. Biologists have a name for the physiologic stress response: fight or flight. It’s the survival response that’s triggered whenever we feel threatened. PTSD triggers similar deep wiring in response to a past trauma or terrifying event. In the context of hospitalization in intensive care, the disorder is called post–intensive care syndrome, or PICS.

  PICS refers to short-and long-term cognitive, mental, and/or physical health problems following a critical illness, with its hallmark being symptoms that get worse after physical recovery. Government stats suggest that up to three-quarters of ICU patients may experience cognitive impairment, and up to 60 percent have PTSD. Even before the COVID-19 pandemic, 5 million people received care in the ICU per year in the US alone, of whom more than 750,000 required mechanical ventilation, as Tom did. That’s a sizable at-risk population and an identifiable condition that’s been largely overlooked. A year later, NIH would describe PICS as a public health burden “due to the associated neuropsychological and functional disability,” but with scant attention to it previously, the agency concluded, “its exact prevalence remains unknown.” Apart from the devastating number of deaths the US and other countries are facing due to the COVID-19 epidemic, thousands of ICU survivors will need both physical and psychological support to heal.

  What we didn’t know is that families of ICU survivors can experience PICS, too. That explained my own hyperresponsive symptoms. Once we recognized all of this as an identifiable problem—a problem that, however difficult, was treatable—we were relieved to discover there were people who could help us.

  These health issues might seem tangential to the superbug story, but they are not. When multi-drug-resistant infections land someone in the hospital, prolong their stay, and present serious additional complications that they and their families must confront, those are the reality of the post-antibiotic world. That’s the reality we all need to wake up to. It’s estimated that 10-15 percent of COVID-19 patients will acquire a secondary bacterial infection, many of which will be superbugs.

  After the success of Tom’s case, Chip and I continue to be approached by desperate patients, almost daily. He and other infectious disease physicians at UC San Diego have treated eleven other patients with intravenous phage therapy, most with success and consulted on a growing number of other phage therapy cases across the US and internationally. Due in part to these efforts, phage therapy is being discussed more openly by researchers, biotech companies, infectious disease physicians, and patients with superbugs who have run out of antibiotic options. In July 2018, Pradeep Khosla, the UC San Diego chancellor, provided Chip and me with $1.2 million in seed funding over three years to launch the Center for Innovative Phage Applications and Therapeutics (IPATH), the first phage therapy center in North America. The day it opened, Science magazine published a commentary in which a respected microbiologist and physician was cited saying that IPATH was “a game changer for the field.” To my delight, I received a congratulatory email from Dr. Hubert Mazure, the great-grandson of Félix d’Hérelle.

  In 2019, Isabelle Carnell Holdaway, a cystic fibrosis and lung transplant patient in the UK, became the first patient to undergo successful treatment with genetically modified phage. The bacterium attacking her lungs was a cousin to that which causes tuberculosis, offering hope that TB might one day be treated with phage therapy. New clinical trials of phage therapy are now underway for patients battling superbug infections associated with cystic fibrosis and implanted medical devices. It will probably be a few years before the data are in, but if these trials show that phage therapy is as efficacious as antibiotics, the FDA will have what they need to make it more widely available. Some researchers are now attempting to use phage therapy to “groom” the gut microbiome to weed out harmful bacteria and promote healthy ones.

  It’s thrilling to play a role in moving phage therapy forward into the twenty-first century, but when your professional and personal lives collide as they did for Tom and me, it changes you forever. Total strangers helped us in our time of need, and we have broadened our efforts to give back, including our decision to write this book.

  As a couple, we don’t take any day for granted, and we don’t sweat the small stuff. A year after he was discharged, Tom took his first swim in the Pacific Ocean since his recovery. When he disappeared under a wave, I called out in a panic to Carly, who was closer to shore: “Where’s your dad?” I could see her grinning as she pointed to a silver head that bobbed up beside her. “Here, silly! He just rode a wave in!”

  Prior to the COVID-19 pandemic, Tom and I started traveling internationally again, including to Africa (over Thanksgiving, of course). Tom has a new bucket list, and Luxor’s Valley of the Kings is still on it.

  I’ve pondered what Robert had told me when Tom fell ill, that I had lived through all the experiences and acquired all the skills to deal with the challenges ahead. All the pieces were there, I just had to look harder to see it and to believe in my ability to get through the challenges each day brought. I believe that
to be true for many of us.

  Tom has reflected deeply on his near-death experiences. If you ask him what he thinks about the three questions the wise men asked him in his desert hallucination, he’ll talk your ear off, but will inevitably say, “A wise person once said, the two most important days in your life are the day you were born and the day you find out why.” He’s still one hundred pounds lighter, but one thing Tom hasn’t lost is his sense of humor. In July 2018, when he was promoted to Distinguished Professor in the Department of Psychiatry, he received a round of applause from his peers. As we toasted his accomplishment over a glass of wine that night, Tom raised his glass and said, “Here’s to the ‘Nearly Extinguished’ Professor’!”

  We’re often asked how our work as HIV researchers prepared us in any way for our year in the grip of a superbug. We’ve mentioned elsewhere in this book how our work with the people and the issues and the science of HIV/AIDS has informed our lives deeply in many ways. Perhaps one of the most relevant, as it affects us all, is something that the documentary filmmaker Janet Tobias recently said to us. HIV researchers and activists believe that the impossible is possible—that it is possible to stop a global pandemic in its tracks, she said.

  It’s true. Tom, me, Chip, Connie, and Davey, all of us came from the testing grounds of the HIV epidemic. In the context of our battle against Tom’s antibiotic-resistant Acinetobacter, for Chip and me, it meant that we never gave up hope that our bold guess would work. For Tom, it was about being resilient, like HIV’s long-term survivors. Choosing to die is easy, he tells me; choosing to live when you are in such incredible pain is much, much harder.

  Not everyone gets to choose. We know that grit and perseverance alone won’t save you from terrible diseases. If that were the case, then so many of those who have died would be alive today. No, what our experience as HIV researchers and survivors of a superbug experience shows us is that when scientific advances, masterful medicine, and the will to live come together, that’s when the impossible becomes possible.

  Steff and Tom on their wedding day in Hawaii (July 26, 2004). Courtesy of authors

  Steff crawling backward into the Red Pyramid, in Dahshur, Egypt (November 25, 2015). Courtesy of authors

  Tom descending into the Red Pyramid, in Dahshur, Egypt (November 25, 2015). Courtesy of authors

  Steff and Tom tour Luxor, Egypt, in a horse-drawn carriage the day he became ill (November 28, 2015). Courtesy of authors

  The MS Mayfair cruise ship, docked in Luxor, Egypt (November 28, 2015). Courtesy of authors

  Tom on a gurney, being loaded into an ambulance outside the clinic in Luxor, Egypt, en route to the CT clinic (November 30, 2015). Courtesy of authors

  Tom in agonizing pain before receiving a CT scan in Luxor, Egypt (November 30, 2015). Courtesy of authors

  Steff takes a photo with Tom while he is fading from consciousness in the ICU at the Uniklinik in Frankfurt, Germany (December 6, 2015). Courtesy of authors

  Tom in a coma, draped in the T-shirt emblazoned with I SURVIVED IRAQIBACTER on his sixty-ninth birthday (February 18, 2016). Courtesy of authors

  Tom in a deep coma, entering multisystem organ failure in the Thornton ICU in La Jolla, California, the day before phage therapy begins (March 14, 2016). Courtesy of authors

  Dr. Robert “Chip” Schooley and Dr. Randy Taplitz prepare to administer phage therapy to Tom for the first time in the Thornton ICU (March 15, 2016). Courtesy of Carly Patterson DeMento

  Scanning electron micrograph (magnification x100,000) of an Acinetobacter baumannii bacterium (stained blue) sampled from Tom, being attacked by some of the phages (stained green) that rescued him. Credit: Dr. Robert Pope, National Biodefense Analysis & Countermeasures Center

  Tom wakens from his coma following a septic shock episode seven days after phage therapy begins (March 22, 2016). Courtesy of authors

  Tom in a wheelchair getting some fresh air with his daughter, Carly Patterson DeMento, outside Thornton Hospital (May 16, 2016). Courtesy of Carly Patterson DeMento

  Tom with Steff at their home in Carlsbad, California, two weeks after being discharged from hospital (August 28, 2016). Courtesy of authors

  Tom’s long road to recovery: working out in the gym (January 2017). Courtesy of authors

  Tom holding a photo of Acinetobacter baumannii beside Steff, holding an image of a bacteriophage (May 2017). Courtesy of UC San Diego Health

  ACKNOWLEDGMENTS

  We succeeded in saving Tom’s life, but thanking all the people who helped do that—and those who supported us in writing this book—is a daunting task. Healing and helping hands reached across the globe, sending cards and messages, lighting candles, bringing meals and care packages, hunting phages, transporting samples, sitting bedside, donating blood, praying, and of course, caring for him and our family. In some cases, we don’t even know their names.

  We owe a debt of gratitude to the staff from the clinic in Luxor, our guide Khalid, the twenty-four-hour medical staff at our travel insurance company, United Health Care Services Inc., and the medevac teams and the ICU at Frankfurt’s Uniklinik, who kept Tom’s condition stable enough so he could be transported safely back to San Diego.

  The medical and nursing team at the Thornton ICU and hospital in La Jolla (now the Jacobs Medical Center) are our heroes, especially Chip Schooley and Davey Smith. From the bottom of our hearts, we thank faculty, staff, students, fellows, and leadership at UCSD Health Sciences, especially those in the Department of Medicine, including faculty, staff, fellows, and students in the Divisions of Pulmonary and Critical Care, Infectious Disease and Global Health, and the Antiviral Research Center. We regret that we could only name a few in this book.

  Huge thanks to Ry Young, Jason Gill, Adriana Hernandez-Morales, Jacob Lancaster and others on the CPT team at Texas A&M, and to the US Navy BDRD, specifically Lt. Commander Theron Hamilton, Biswajit Biswas, Captains Mateczun and Stockelman, Commander Matthew Doan, Lt. Commander Luis Estrella, Matthew Henry, and Javier Quinones, for their tireless work to generate phage cocktails for Tom. An unsung hero is Dr. Cara Fiore from the FDA, who went beyond the call of duty to connect us to phage researchers and to fast-track the necessary approvals. We also thank the leadership from AmpliPhi Biosciences for donating a phage, and researchers from India, Switzerland, and Belgium who offered phages as well. Forest Rohwer, Anca Segall, and their labs at San Diego State University, especially visiting postdoc Jeremy Barr, and PhD student Sean Benler, who saved the day by stepping in to repurify the first phage cocktail on a moment’s notice. Carl Merril and Maia Merabishvili provided critical advice on phage dosing, administration, and safety, and Charles Dinarello on endotoxin levels.

  Our families played a critical role in supporting us in so many ways. My dad, Al Keith, died before this book was complete. After reading an early draft, one of his last words to us was “Bravo!” Our daughters Carly and Frances, and their mom Suzi; son Cameron; and Danny were lifelines. My mom, Heather; sister Jill and her daughters, Rylie and Morgan; and my sister Jennifer, her husband, Pete, and their kids, Ella and Nathan, were always there for us.

  We are indebted to Martin Feisst and Robert Lindsy-Milne for their energy, intuitive advice, and support. Countless friends, students, postdocs, faculty, and staff who are too numerous to name kept our spirits from flagging with visits, dinners, phone calls, and running errands, which meant the world to us. Friends on Facebook and Twitter gave us the encouragement we needed to work on this book, even when the memories were painful.

  Special thanks to our friend Jon Cohen and his wife, Shannon Bradley, who not only visited Tom and nourished our family repeatedly, but who also provided helpful advice that helped us find both an amazing agent and a publisher.

  In writing this book, we stayed as close to the true story as possible, referring to fifty-two pages of my Facebook entries, over three thousand pages of Tom’s medical records, scads of email threads, and conversations with those involved when memories got fuzzy. In a few ca
ses, we changed names to protect people’s privacy, but in most cases, real names were used.

  We are grateful to many individuals who repeatedly checked drafts of this book for accuracy. Chip Schooley and Davey Smith checked medical details and descriptions, and Liz Greer painstakingly corrected several drafts, even after losing her husband, Doug, to pancreatic cancer not long after Tom came home. Carly and Frances Patterson, Cameron Strathdee, Trish Case, Joe DeSommer, Judy Auerbach, Diana McCague, Steve Weiner, Kristen Rau, and Margaret Browning provided advice on readability. Hubert Mazure, Bill Summers, Betty Kutter, Gordon Wheat, Bob Blasdel, Ry Young, Biswajit Biswas, Theron Hamilton, Jason Gill, and Carl Merril provided clarifications on historical and scientific details. Brian Kelly sought attributions for quotes and obtained necessary permissions. Dr. Robert Pope provided a scanning electron micrograph of Tom’s Acinetobacter being attacked by Navy phages. (We have an enlarged copy we throw darts at.)

  This book would not have been published if it wasn’t for our agents, Gail Ross and Dara Kaye at Ross-Yoon, who believed in us and saw us through many proposal drafts. We are equally grateful to our executive editors, Michelle Howry, Amanda Murray, and Krishan Trotman; copy editor Lori Paximadis; art director Amanda Kain; our publicist, Joanna Pinsker; and our publisher, Mauro DiPreta from Hachette Book Group, for their unwavering enthusiasm, support, and wisdom. We also thank Ilsa Brink for our terrific book website: ThePerfectPredator.com.

 

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