Podovirus

Jessica Sacher and Joseph Campbell

Phages (bacteriophages) are viruses that kill bacteria with sniper-like precision. They can be incredibly useful for treating life-threatening infections ('phage therapy'), and can help us reduce our dependence on antibiotics. They've been known for 100 years... so WHY do we still not see them on the shelves? Jessica Sacher, PhD (Staff Scientist at Stanford and cofounder of Phage Directory) and Joseph Campbell, PhD (former NIAID program officer) talk to phage therapy practitioners, researchers and entrepreneurs to understand one question: why don't we have phage therapy yet?

  1. 20H AGO

    How to run a phage therapy center from your academic lab

    What does it take to build a phage therapy program from nothing — and keep your research lab running at the same time? In this episode, Joe and I sat down with Dr. Daria Van Tyne, PhD, Associate Professor of Medicine at the University of Pittsburgh and researcher in the Division of Infectious Diseases at UPMC. When Daria arrived at Pitt in 2018, she describes herself as "phage poor" — a lot of interest in phages, zero phages in hand. Today, her lab manufactures phage for dozens of compassionate use patients per year, all while continuing to publish research. Daria's commitment to owning the process end to end is especially fascinating to hear about — right down to personally doing the phage formulation herself every morning after preschool drop-off, because, as she put it: "if I'm making something that's going to be administered intravenously to patients, I want to be the one to own it." 🔬 Highlights: Building a phage library from scratch: How Daria used multidrug-resistant clinical isolates as bait to fish phages out of hospital and municipal wastewater — ensuring clinical relevance from day one. The first cases: From a cystic fibrosis patient post-lung transplant with Burkholderia multivorans in 2020, to partnering with Ben Chan at Yale and Breck Duerkop at Colorado when they didn't have the right phages in-house. Making manufacturing sustainable: Only using phages so good undergrad students can make them grow reliably, batching workflows, pre-manufactured cocktails, protein low-bind tubes, and more. QC that works for her lab and the FDA: Whole genome sequencing for identity and purity, cesium chloride banding, endotoxin testing, USP-71 sterility. Working with the FDA: From nerve-wracking Friday evening conference calls for emergency INDs to the much calmer world of single-patient INDs and email correspondence — and why she sees the FDA as a partner, not a gatekeeper. The phage susceptibility testing problem: Why the field still lacks standardized, clinically translatable assays, and what it would take to make phage susceptibility testing work in a real clinical microbiology lab. Research questions that keep her up at night: Phage resistance evolution in patients, whether phages can clear biofilm infections, and what phage therapy actually does to the microbiome. The future she's hoping for: FDA-approved phage products, with compassionate use and clinical trials coexisting for the long tail of complex cases — and her biggest fear being that investor money kills the collaborative spirit that has made the field work. 📺 Watch on YouTube: https://youtu.be/nbN4whcoJrU 🔗 Learn more: Pittsburgh Phage Program (P3): https://dom.pitt.edu/id/research/phage/

    54 min
  2. 11/13/2025

    AI-generated phages that work: ChatGPT for phage biologists?

    Can AI design living organisms from scratch? Samuel King and Claudia Driscoll from the Arc Institute used genome language models to generate functional phages—and 16 of them actually worked in the lab. Not only that, they killed bacteria equally or better than the natural phage the team used as a template.  In this episode, we dig into how they did it, what it means for phage research, and why this could be a new way to explore evolution and design genomes. What we covered: • How genome language models work (ChatGPT, but for DNA) • Training on millions of phage genomes with Evo-1 and Evo-2  • The creativity (from biologists!) required to figure out how best to filter generated sequences • Going from 4000 selected sequences in silico, to 300+ synthesized candidates, to 16 working phages • Fresh phage lab protocols for new ways to look at phage fitness • Phage "personalities" that emerged from the generated candidates • Watching recombination occur among a cocktail of designed phages • Cost realities: hundreds of dollars per 5kb genome candidate, but emerging ways to reduce it exist! • Good news: All tools are open source and free to use! The preprint: Samuel H. King, Claudia L. Driscoll, David B. Li, Daniel Guo, Aditi T. Merchant, Garyk Brixi, Max E. Wilkinson, Brian L. Hie (2025-09-17). Generative design of novel bacteriophages with genome language models | bioRxiv. biorxiv.org. Retrieved November 8, 2025, from https://www.biorxiv.org/content/10.1101/2025.09.12.675911v1 More resources: • Arc Institute Evo browser interface: https://arcinstitute.org/tools/evo • GitHub (open source code): Evo2: https://github.com/ArcInstitute/evo2)  • Hugging Face (model downloads): https://huggingface.co/arcinstitute Guests: Samuel King: PhD candidate, Stanford/Arc Institute, Brian Hie's lab; follow @samuelhking on X Claudia Driscoll: Postdoc, Arc Institute, Brian Hie's lab, follow @driscoll_cl on X Also follow @BrianHie, @arcinstitute, @stanford on X for more from this team!

    1h 4m
  3. 08/15/2025

    How to get successful outcomes with phage therapy: Saima Aslam, MD, MS

    "When I first started, I was treating anything and everything in terms of ‘this is highly drug resistant and it's failed’. But I think I have a clearer idea now, at least clinically, where I think phage would be beneficial, rather than all comers.” What does it take to achieve an 85% success rate with phage therapy? We talk to Dr. Saima Aslam, MD, MS, a Professor of Medicine at UC San Diego and the clinical lead of IPATH (Center for Innovative Phage Applications and Therapeutics), about her strategies for successful phage treatment.  Since 2017, Dr. Aslam has treated many patients with phages, and learned crucial lessons about patient selection, trial design, and the importance of collaboration between clinicians and phage researchers. We explore how her approach has evolved from "treating anything and everything" to targeted strategies, why early clinical trials struggled, and her exciting NIH-funded placebo-controlled trial for recurrent UTIs in kidney transplant patients.  The conversation covers practical implementation challenges and lessons for phage therapy practitioners, and discusses her vision for a centralized US phage repository and manufacturing center to reduce the current 6-12 month delays in accessing treatment. Here's a taste of what we covered: 1. 🧫 Why patient selection is crucial: not all infections benefit equally from phage therapy 2. 🏥 Why phage scientists and clinicians must work together from day one 3. 🧪 Learning from early studies to create pragmatic, enrollable protocols 4. ⌛ The challenge of long-established biofilms in chronic infections like LVAD bacteremia 5. 💉 Why recurrent UTIs in transplant patients represent the "lowest hanging fruit" 6. 🔬 How Dr. Aslam designed her NIH-funded clinical trial for recurrent UTIs in kidney transplant patients 7. 🌐 The urgent need for centralized phage production in the US to reduce treatment delays Chapters: 00:00 Introduction to Phage Therapy and Dr. Saima Aslam 02:11 Early Experiences and Lessons in Phage Therapy 05:27 Criteria for Patient Selection in Phage Therapy 09:14 Challenges in Phage Therapy: Availability and Effectiveness 12:31 Collaboration and Research in Phage Therapy 24:08 Bottlenecks in Phage Therapy Development 36:07 Future Directions and Hopes for Phage Therapy Learn more: Saima’s team is now enrolling for their kidney transplant phage clinical trial! (https://clinicaltrials.gov/study/NCT06409819) A recent paper by Saima and her team: Phage Therapy in Lung Transplantation: Current Status and Future Possibilities (https://pubmed.ncbi.nlm.nih.gov/37932113/)

    54 min
  4. 06/27/2025

    Dr. Marisa Azad, MD, PhD: Behind Canada's first prosthetic joint treatment with phage therapy

    "It's unacceptable to just tell this poor patient, there's nothing I can do to help you... That's when I thought, okay, well, what about kind of pushing the boundaries a bit here and thinking about phage therapy?" - Dr. Marisa Azad Join us for an inspiring conversation with Dr. Marisa Azad, a clinician-scientist at The Ottawa Hospital who is pioneering the treatment of chronic infections using phage therapy. Dr. Azad shares her journey from microbiology PhD to orthopedic infectious disease specialist, and how a desperate patient case led her to become the first in Canada to use phage therapy for prosthetic joint infections. Here's a taste of what we covered: 1. 🦠 The challenges of treating orthopedic infections, and how the problem is typically being dealt with in Canada (hint: MULTIPLE repeated surgeries for years is normal) 2. 🧪 How Dr. Azad navigated regulatory hurdles to bring phage therapy to Canada, and what it was like working with Health Canada (Canada's FDA) to get approval 3. 💉 Insights on phage administration and patient immune responses: what she's learned and what barriers she sees 4. 🔬 The importance of collaboration in advancing phage therapy research, and what's left for researchers to figure out 5. 👩‍🔬 How crucial it is to support women in science and medicine, still in 2025, especially in innovative fields that require taking steps your field isn't taking (which require extra bravery and support systems!) 6. 🏥 Bridging the gap between basic science and clinical practice: how Dr. Azad weaves together both ways of thinking, all with patient benefit as her central driver You can also watch the episode on YouTube: https://youtu.be/5TKhgFplvfU Want to learn more? - CBC (Canada's national news outlet)'s coverage of Dr. Azad's successful case, and how patient Thea Turcotte recovered - Dr. Azad's recent publication on phage therapy for PJI (an n-of-1 clinical trial) - Our recent Podovirus interview with Cytophage CEO Steven Theriault, whose Winnipeg-based company prepared the phages for Dr. Azad's patient, and who is partnering with her as the phage manufacturer for future cases - Since Dr. Azad's success last year, Health Canada is beginning to enable more phage therapy: a PJI phage treatment has just taken place in Calgary by a separate group — watch the news segment here

    49 min
  5. 06/02/2025

    How to navigate regulatory limbo: a Canadian phage therapy CEO's playbook

    "Phages are not drugs. Every time they say, 'Did you go through regulatory?' I say, 'I can do regulatory, but I'm not a drug.' There's 145 components of the regulatory requirements that I don't fit in." When your health innovation doesn't fit existing regulatory boxes, how do you build a business? Steven Theriault, CEO of Cytophage, has spent 9 years learning to navigate Canada's regulatory maze for phage therapy. From being told "we don't know" by government officials to raising $24M and treating patients, Steven shares his hard-won playbook for building in uncharted regulatory territory. In this episode of the Podovirus Podcast, Jessica Sacher and Joe Campbell talk to Steven Theriault about what he's tried, accomplished and learned in the last ~decade building a phage biotech company in Canada: 🎯 The pivot strategy: When hospitals won't buy your innovation, find another market (Steven turned to chicken farmers when Clorox contracts blocked hospital sales)  🏛️ Educating regulators: How to teach government officials about your technology when they've never heard of it (Steven went from 10 officials with no idea what a phage was, to regular advisory calls to shape Canada's approach to regulating phage therapy) 📋 Creating your own framework: Why Steven argues phages need different GMP guidelines than traditional drugs, and how to advocate for biological variability  💰 Funding the unfundable: How Cytophage raised $24M for technology that doesn't fit traditional pharma investment models 🔄 The workaround approach: Building revenue streams (agriculture) to fund your real mission (human health) when direct paths are blocked 🌐 International advantage: Why Steven has more regulatory traction in the US than Canada, and how to leverage global progress domestically Learn more: Cytophage website: https://cytophage.com/ Steven's 2024 TEDx talk on the future of phage therapy: https://www.youtube.com/watch?v=OyfbKOLNlWg The CBC News story on Cytophage's first patient treatment: Thea's success story: https://www.cbc.ca/news/canada/manitoba/phage-therapy-infection-1.7156333

    1 hr
  6. 05/09/2025

    Why can't patients access phage therapy? Does FDA need to change, or do patients just need a voice?

    "This feels just like the early days of the HIV crisis. People are dying, you're not hearing about it. We need a group like ACT UP to bring this to the public. We're not going to get phage therapy until people start demanding we have it."  On this episode, we talk to phage therapy patient advocate Chris Shaffer about how he fought for access to phage therapy to save his own life, and how it's led him to advocate on behalf of other patients being told there's "nothing left" for their infections.  He draws parallels between phage advocacy and 1980s AIDS activism, while sharing his successful treatment journey to Tbilisi, Georgia for phage therapy. He shares his vision for a patient-centered future where anyone, not just the well-connected or the lucky, can access phage therapy if it could help them.  Here's a taste of what we covered: 1. 🦠 Chris's battle with a drug-resistant infection that antibiotics couldn't cure, and how after two years of suffering, he was completely cured in just four months with phage therapy 2. 🧪 The major obstacles to phage therapy access in the US: lack of awareness among doctors, patient trust issues, and difficulty finding phages that match specific infections 3. 🏥 The striking cost difference: Chris's complete phage treatment at Eliava (including doctor visits, tests, and therapy) cost $4,600 vs. $10,000+ for just a single round of IV antibiotics in the US 4. 🔬 How the FDA actually considers phages safe enough that they don't require the same safety testing as antibiotics - but this information isn't reaching patients or doctors 5. 📢 Why Chris believes we need more vocal advocacy similar to the HIV/AIDS movement in the 1980s-90s to push for greater phage therapy access 6. 📱 Practical ideas for improving access through non-profit phage centers, better education for medical students, and targeted communication strategies Learn more: - Chris Shaffer's book about his phage therapy journey: https://www.amazon.com/FINDING-PHAGE-Partnered-Bacterial-Superinfection/dp/1733418296 - Chris’ website: https://phagetherapyusa.com/ - Case study on Chris’ case, published in the International Journal of Clinical Virology: https://www.clinvirologyjournal.com/articles/ijcv-aid1059.php - Eliava Phage Therapy Center in Tbilisi, Georgia: https://eliavaphagetherapy.com/  - 2021 FDA-NIAID Workshop on Phage Therapy transcripts mentioned during the conversation: https://www.fda.gov/media/159401/download - Pranav Johri's case study that helped Chris trust phage therapy: https://pubmed.ncbi.nlm.nih.gov/37790805/ - An youtube interview we did with Pranav about his story: https://www.youtube.com/watch?v=V-Qso4q52CY - An interview we published in Capsid & Tail on Pranav's story: https://phage.directory/capsid/phage-therapy-access-india#article - The PASTEUR Act, which Chris mentions: a bill in US congress (still has not passed) on changing how antimicrobials can be paid for by the government: https://www.contagionlive.com/view/an-update-on-the-pasteur-act

    1h 12m
  7. 05/02/2025

    Finally, phase 2 data! Inside BiomX's successful phage therapy trial with CEO Jonathan Solomon

    "Finally, finally we have Phase 2 data. We put a dent in the theory that phage therapy doesn't work. Maybe it does work. Maybe it's worth taking a risk." Jonathan Solomon joins Jessica Sacher and Joe Campbell on the Podovirus Podcast to discuss BiomX's exciting Phase 2 clinical trial results, where they used bacteriophages to treat diabetic foot osteomyelitis (DFO). With 40% of DFO patients facing amputation, this is an area of massive unmet need. Jonathan shares how their trial was designed (he credits the team at Adaptive Phage Therapeutics, which began the trial prior to its merge with BiomX), and how it achieved what many of us have almost given up on: positive, statistically significant clinical efficacy data for a phage therapy treatment*. Here's a taste of what we covered: 1. 🔬 The "Head of the Snake" theory – why many diabetic foot ID docs believe targeting Staph aureus alone works even in polymicrobial infections 2. 💉 Their phage delivery approach: combining IV "debulking" with topical phage application to help break down biofilms 3. 🏥 How 12 out of 13 phage-treated patients with bone-deep ulcers showed significant tissue rebuilding vs. only 5 of 9 in the placebo group 4. 💰 The commercial viability challenge: "If you're not seeing a 30% improvement, no one would pay for an expensive phage therapy" 5. 🧪 How personalized medicine meets practicality – the decision to use just one optimized phage per patient 6. 🔭 BiomX's dual-program approach with both DFO and cystic fibrosis trials showing promising results Learn more! 1. BiomX Positive Phase 2 Diabetic Foot Osteomyelitis Results 2. The details of BiomX/Adaptive Phage Therapeutics’ DANCE trial 3. Recent key opinion leader discussion of Diabetic foot osteomyelitis results 4. BiomX Positive Part 2 Phase1b/2a trial of Cystic Fibrosis results 5. BiomX (NYSE: PHGE) website *Added context Timestamp ~22:50: Technophage (a biotech company in Portugal) did run a prior Phase 1/2a trial for diabetic foot infections. While the study showed their TP-102 phage cocktail was well tolerated and safe, and reported improved outcomes, the authors report it was underpowered to determine the superiority of TP-102 over placebo, as it ended before reaching the final target of 18 patients due to slow recruitment. Technophage is currently running a larger version of this study.  Of note, there has been one other successful phase 2 phage trial: the Wright et al. ear infection trial published in 2009. This clinical program would have moved to phase 3, but corporate priorities shifted around the time of the ‘08 crash, and it was dropped (check out this interview with trial lead David Harper to learn more). Phage companies have been trying to re-reach this milestone ever since. Finally, it’s been reached.

    58 min
  8. 04/09/2025

    Does every scientist need an AI co-scientist? How two professors solved a years-long viral mystery

    "I was so biased. I knew too much and that's why we couldn't see the obvious answer that was right in front of us for years." In this episode of the Podovirus Podcast, we explore the intersection of AI and phage biology with Professors José Penadés and Tiago Costa from Imperial College London. They share their recent discovery about phage-inducible chromosomal islands (PICIs) and how Google's new (not-yet-released) AI co-scientist tool independently reached the same conclusions they had spent years working toward—revealing how tailless phage capsids can bind with different phage tails to expand their host range. Here's a taste of what we discussed: 1. 🧬 First, the biology: José and Tiago discovered that sometimes the end product of a viral lifecycle isn't infectious (yet). It might instead float around as a half-virus (a 'tail-less capsid'), and even mix and match with halves (tails) of other viruses floating around, enabling it to get into a vast array of totally different cells with one simple genetic code. This is the story of PICIs (phage-inducible chromosomal islands).  2. 🤖 How Google's AI co-scientist tool—without access to their unpublished data on this project—accurately proposed the hypotheses and experiments it took them years to come up with (because they seemed to go against dogma in the field) 3. 🔬 Why 'knowing too much' can be an obstacle to discovery in science, the beauty of an unbiased companion, piecing apart what they would have done differently if they'd had AI all along, and how José and Tiago will be using AI tools going forward Chapters 00:00 Introduction: AI + phage research, and why we wanted to talk to José and Tiago! 02:10 First, the biology background: exploring PICIs (phage-inducible chromosomal islands) and their significance 10:13 The role of AI in hypothesis generation 19:08 Interpreting data and overcoming bias 28:40 Future implications of AI in phage therapy 37:25 Experimental evidence and hypotheses validation 40:46 AI tools and their effectiveness 44:38 Interpreting AI outputs and experimental design 51:30 The role of AI in scientific discovery 57:30 Future of AI in research and collaboration Papers discussed: 1. José and Tiago's new preprint on the science of PICIs: https://www.biorxiv.org/content/10.1101/2025.02.11.637232v1.full 2. Their companion preprint on exactly how they worked with the AI co-scientist (+ benchmarking against other AI tools!): https://www.biorxiv.org/content/10.1101/2025.02.19.639094v1  More info about Google's AI co-scientist: https://research.google/blog/accelerating-scientific-breakthroughs-with-an-ai-co-scientist/ More info about their research:  José's lab: https://profiles.imperial.ac.uk/j.penades/about Tiago's lab: https://profiles.imperial.ac.uk/t.costa Want to learn more about phage satellites? Check out this new Nature Reviews Microbiology by José's team: https://www.nature.com/articles/s41579-025-01156-z

    1h 9m

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About

Phages (bacteriophages) are viruses that kill bacteria with sniper-like precision. They can be incredibly useful for treating life-threatening infections ('phage therapy'), and can help us reduce our dependence on antibiotics. They've been known for 100 years... so WHY do we still not see them on the shelves? Jessica Sacher, PhD (Staff Scientist at Stanford and cofounder of Phage Directory) and Joseph Campbell, PhD (former NIAID program officer) talk to phage therapy practitioners, researchers and entrepreneurs to understand one question: why don't we have phage therapy yet?