Steffanie Strathdee is the Associate Dean of Global Health Sciences, Harold Simon Professor at the University of California San Diego School of Medicine and Co-Director at the Center for Innovative Phage Applications and Therapeutics. She is also part of a growing number of scientists championing research that investigates how bacteriophages can be used to treat bacterial infections. Her recent book, The Perfect Predator (Hachette Books), tells the story of her husband’s near-fatal brush with antibiotic resistant bacteria and how experimental phage therapy made the difference between life and death.
SCIENTIFIC INQUIRER: Amazing story. Prior to your husband’s illness, what level of awareness did you have regarding the antibiotic resistance crisis growing around the world?
STEPHANIE STRATHDEE: I knew it was a growing problem, and that governments around the world weren’t doing much to solve it. However, I had no clue that by 2050, it’s estimated that one person every three seconds will die from an antibiotic resistant infection, nor that antimicrobial resistance (AMR) is a bigger and more immediate threat in our lifetimes than climate change. But believe me, I know now!
SI: How did your experience as an HIV epidemiologist prepare you for your experience, if at all?
SS: As a scientist, I knew how to conduct a literature research. As an HIV epidemiologist, I knew the basics of microbiology and virology. I’d heard of phages in class as an undergrad, but I didn’t know that they had been used to treat bacterial infections. I’d seen people –my PhD advisor and good friends – waste away and die terrible deaths. And most of all, I was familiar with the concept of fighting a disease that no one was paying attention to, one that our narrow-minded policies are actually making worse and not better. As a result of my work with communities affected by HIV, I know how important advocacy is, both for the disease and experimental treatments that need more research.
SI: It’s a story with lots of peaks and valleys, what was your highest high and lowest low?
SS: My lowest low was the day the doctors told me and Tom’s daughters that they thought he was going to die –and within days. The phages weren’t ready yet and no one knew if they could cure him. I was basically asked if I wanted to pull the plug or not or start kidney dialysis within the next few days. It was gut wrenching not knowing if I was prolonging his agony for a shot in the dark.
My highest high was the day that he opened his eyes after he’d lapsed back into a coma, and kissed me. His lips were cracked and caked with spittle, but I didn’t care. I was witnessing a miracle.
SI: There seems to be enough momentum in terms of basic research and industry to really move forward with developing phage therapy. What is the current state of development?
SS: The rapid pace of development has been nothing short of astounding. At least 50 patients have been treated with phage therapy in North America and the UK. It’s still experimental, but hospitals, governments and patients are getting more familiar with it.
At my university, we’ve opened the center for Innovative Phage Applications and Therapeutics (IPATH) which is the first phage therapy center in North America. Several clinical trials are being planned, including two at IPATH.
In May 2019, the world’s first report of a genetically modified phage to successfully treat a patient was published; her treatment was based on Tom’s case. Her bacterial infection was Mycobacterium abscessus, which is in the same genus as tuberculosis. This lends hope that one day, TB might be treated with phage therapy.
Finally, the prospect of using gene editing techniques to ‘tweak’ natural phages has brought new energy and resources to the field, because genetically engineered or synthetic phage can be more easily patented. That is very exciting to biotechs and Big Pharma. We’ve also learned that phage can re-sensitize bacteria to antibiotics they were resistant to, so they can play a role in resurrecting antibiotics that were being put out to pasture due to AMR.
SI: What are some of the hurdles that still need to be overcome for phage therapy to take the next step?
SS: There are several. We need more basic research to understand the interplay between phage, bacteria and the immune system, as well as phage-antibiotic synergy. We need to study which aspects of phage lifestyle need to be tweaked with genetic engineering to make them perform optimally.
For example, the phage for some bacteria, like C. difficile, Mycobacterium sp. or Borrelia sp. tend to be temperate. In our book, The Perfect Predator, I describe these phages as entering the bacterial cell and “hitting the snooze button” rather than lytic phages that go on a “phage rage” where they turn the bacterial cell into a phage manufacturing plant before blowing it up.
We want to treat people with the lytic kind, which means figuring out ways to convert temperate into lytic phage, which may differ for each kind of bacterial pathogen. We need to figure out the best way to dose patients; we can calculate how much phage we are administering to the patient but since phages multiply, the ‘dose’ they actually receive isn’t really known. We also need regulatory pathways in cases like this, where the “drug” is alive.
SI: Can you tell us about the UC San Diego center for Innovative Phage Application and Therapeutics (IPATH) and the work being done there?
SS: At IPATH, we’re fielding inquiries from patients and doctors on a daily basis that are looking for phage therapy, and in cases where patients are eligible, we are working with labs around the US and Canada to find phage to match their bacterial isolate so that they can get treated. We’re planning two clinical trials that we hope to launch in 2019. And we’re hoping to raise funds to develop a global repository of superbugs and a matching one for phage so that it will be much easier to find matching phage to treat patients and to conduct clinical research to move the field forward.
SI: As much as your book is about the promise of phage therapy, it is also very much about antibiotic resistance. Tom fell ill in Egypt and was taken to a top Egyptian hospital. Nonetheless, the level of care was still lacking, though by no fault of the doctors. Outside the major cities, the quality of healthcare drops precipitously in developing countries. Lack of access to quality care and proper diagnostics causes serious stewardship problems in resource poor environments. Are there any solutions to this problem?
SS: The solution needs to be multi-pronged. At a structural level, we need governments to take the global crisis of AMR seriously. That means developing and enforcing policies that reduce the spread of AMR, such as banning the use of antibiotics as growth promotors in livestock, or spraying citrus with antibiotics. We need low cost, point-of-care diagnostics to enable doctors to diagnose bacterial infections quickly, along with antibiograms that allow rapid clinical decision-making about which antibiotics are appropriate to treat a patient.
If phage libraries existed around the world and there was approval and expertise to use them, phage therapy could be also be an important part of the solution, either as an adjunct to antibiotics or a replacement in cases where there are no antibiotic options left. Sadly, those cases are becoming all too common.
SI: On a scale of 1-10, knowing what you know, how likely are we to have viable and accessible phage therapy medicines in the next 20 years?
I’m an optimist. And based on how quickly the field is moving forward, I’ll bet 100%. In The Perfect Predator, one doctor described our attempts to cure Tom with phage therapy as a hail mary pass in the last minute of the game where the quarterback is throwing the ball 100 yards down the field, but he’s blindfolded. That’s no longer the case. I’m really proud that Tom’s case, and our story, has played a small part in making medical history.
To order a copy of The Perfect Predator, visit Hachette Books. For more information about phage therapy visit the Center for Innovative Phage Applications and Therapeutics.
IMAGE SOURCE: Hachette Books; Creative Commons
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