This week, I’m excited to share my recent conversation with Joe Campbell, former program officer at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Joe played a key role in shaping phage research funding during his tenure at NIAID. He reflects on his career, the evolution of phage therapy research, challenges and opportunities he sees for the field, and shares wisdom into the grant funding process.

Listen to the conversation on the Podovirus Podcast!

Or watch it on Youtube!

Jessica Sacher: Welcome to the new Podovirus podcast, which we started to give ourselves another channel to talk to the phage community. I’ve been wanting to have conversations with key phage people, and I like to do that in a conversation rather than always interviewing them on a blog or through email. I’m glad that I could have convinced you, Joe, to talk to me about your career, because I think it’s a really special turning point that you have been an NIH program officer, kind of overseeing all of our phage work for so long. I was hoping we could talk about your reflections on your career and the phage field and where we’re at. Maybe we’ll get into some wisdom, but I think we should just take this where it goes. It’s always fun to talk to you, and this is kind of a new experiment with the podcast. So let’s just record the conversation. Maybe I’ll pass it to you and you could just give an intro to those who haven’t been following your role in the phage field so far.

Joe Campbell: I was a bench scientist for a large portion of my professional career, and then I left to start doing program stuff around 2008. I came to NIAID in 2011, and the phage work really started three or four years after that. As some of you may know, there was an outbreak of antibiotic-resistant Klebsiella at the NIH Clinical Center. One of my program colleagues, Jane Knisely, was contacted by someone in the clinical center about whether we, in the program, could help find phages to kill the Klebsiella outbreak strain at the NIH.

Jane started a bacteriophage interest group, and I took over, I think around 2015. At that time, we were doing several things. We had a bacteriophage interest group which started out as just NIH people, NIAID people. Then we started adding FDA people. As some of you may know, we had a few workshops. We had an NIAID FDA workshop in 2015 and 2017, and we had one in 2021.

We started having speakers come in just to speak to us in person, and then when COVID happened, we started inviting people from around the country and then eventually around the world to speak remotely. It sort of grew into a bigger and bigger thing. I was fortunate to be there at an exciting time, and people seemed to enjoy the seminar series. Of course, NIAID was doing various things through grants and contracts to support the development of phage therapy. I was fortunate enough to be invited to various Phage Futures and Phage Summit Conferences. I think that’s where I first met you, at the Phage Futures.

I just sort of ended up networking with more and more people. At the beginning of this year, at the end of January, I decided I would leave NIAID. I am now consulting for a couple of companies, and I’m working with Phage Canada, which is run by Greg German and others out of Toronto. So I’m keeping busy. I just got back from the Viruses and Microbes conference in Australia, which was fun and interesting. That’s sort of my phage therapy life in a nutshell.

Jessica: Yeah, awesome. So you haven’t actually retired because now you have a bunch of different new jobs.

Joe: No, I mean, it’s been exciting to be able to do a little bit of picking and choosing what I did and didn’t want to do. Working with the companies is exciting. I think Phage Canada is trying to get sort of towards the place where Phage Australia maybe is already. So we’ll see what happens, and I’m happy to be helping with that.

Jessica: Yeah, that’s awesome. I’ve been thinking back to when we started Phage Directory, and I think we talked to you early on at one of those phage meetings. I was hearing a lot around that time that NIH won’t fund phage therapy, and everyone was passing around their failed grant proposals. It was like they just had a red line through it saying phage therapy won’t work. Do you feel like that was how it felt for you on your end? Was there a time where it was kind of hard for anyone to get phage funding or for NIAID to take it seriously, or was that kind of just the impression that people had?

Joe: It was a little bit of both. I think partly, and I’ll give credit to Jane, she sort of spearheaded the effort to put out that phage-specific call for grants. I think that makes a big difference because when people apply for phage therapy grants, certainly when they’re competing with other modalities of treating AMR infections, there is a large bias against or skepticism towards that approach.

That was one of the reasons we felt like we needed to put out an initiative that was only for phage grants. So the phage grants would be competing with other phage grants, and we’d have a study section. The composition of the study section would be phage people who wouldn’t hopefully have some of the biases against their own field. We can talk about how fair or unfair the reputation in the West is about phage therapy in the East and how that influenced the way study sections reacted to it.

I guess I wouldn’t say that NIAID was against it. It’s just that if you don’t put out grants that will be reviewed by people who are in the phage field and you’re sort of taking all comers in the AMR field, especially five or 10 years ago, you were gonna get that result. People were gonna say, “Phage? We’re more comfortable with small molecule approaches.”

Jessica: Got it. Do you feel like the outcome of that R21 grant, when you think about the grants that were funded or the groups that were funded, have you seen them go on to get R01s and continue building?

Joe: That’s a good question, and I don’t have the ability to look at that anymore because I don’t have the data the way I would have when I was still at NIAID. I guess I’ll turn the question on you. Do you have a sense that people don’t feel that it’s as hard to get phage grants as they did at the time you were talking about?

Jessica: Yeah, good question. I think I don’t have the same sense anymore that they’re feeling like it’s a red stamp and thrown out at all. People have shifted in what they’re talking about, and it’s about the specifics, like when we put in this grant, will we collaborate with this group or not? The conversation seems to have advanced, and it’s no longer, “Will the NIH ever consider phage therapy?” I certainly don’t hear that anymore.

Joe: Yeah, and I mean, I know people have even gotten phage therapy grants in other ICs, like for treatment of specific infections in heart or kidney, that were being funded by the institute that was interested in hearts or kidneys. So it wasn’t just the infectious disease division, NIAID, that was funding phage therapy grants. So yeah, I think it’s kind of shifting.

Jessica: Do you feel like when you and Jane were kind of pitching this idea internally, did you have to make a case for sending out the R21 at that point? Was that hard for you guys to get through, or could you kind of say this is what we think and everybody kind of agreed and backed you on that?

Joe: Well, I mean, and I think Jane did most of the heavy lifting on this, but Jane and I talked about it, and Jane had to present it to our division. About that time, NIAID was coming up with plans on how we were going to deal with AMR, and phage therapy would be one of six or seven things that would get mentioned in there. So it’s a lot easier to convince people if the Institute has published a document saying this is one of the approaches we think is good.

When you’re trying to argue that we should set aside money for a specific kind of grant, one of the first questions you’re asked is how does it fit in with the NIAID mission statement? When you have a document of how NIAID thinks we should deal with AMR and phages are included in it, that’s at least half the battle.

Jessica: Got it. OK. So you kind of were able to just tie it back to that, and it was kind of straightforward from there.

Joe: Yeah, I mean, I think there’s a pretty great awareness among NIAID leadership of how serious the AMR threat is and how much we need to not ignore any possible route of treatment, whether it be some novel class of traditional antibiotics or lysins or phages or, for C. diff, people are doing fecal microbiome transplants. We’re reaching a point where AMR is enough of a crisis that we can’t leave stones unturned.

It’s never a good idea to leave stones unturned, but really now we’re at a point where we’ve got a lot of momentum from the Patterson case, certainly, and some of the other compassionate use cases. But the Patterson case really kind of launched us to just ride that wave.

Jessica: And I do think having Steffanie Strathdee and Chip Schooley, Steffanie of course is Tom’s wife and Chip is a friend of Tom and Steffanie’s, and for lack of a better term, they had street cred in the ID world, so that helped overcome some of the skepticism.

Joe: Chip and Steffanie, but Chip for a great part, understand how the ID world thinks. They both do, and just having someone who had a big reputation, two people really, who had a big reputation in the AIDS community being involved in it just made a huge difference, I would say.

Jessica: I want to ask you, coming back to what you were saying about Phage Canada and Phage Australia, how do you think about the idea of these phage therapy centers, which I’ve been loosely calling them, versus people that are pursuing approaches just like as a biotech company, the more traditional approach? Do you see a role for both, or are you trying to coax centers to kind of pick a product and take it through clinical trials and advance it that way? Or how are you thinking about these?

Joe: You know, I was actually before the Viruses of Microbes meeting at a meeting where the Gates Foundation was talking about phage therapy. So we’ll see what, if anything, they do. I’ve often thought about this. Let’s say, instead of a phage cocktail, Tom Patterson had been treated by a very narrow-spectrum pill. I don’t know that that would be approved either. So I don’t know if it’s just phage. And I guess the point I’m making here is that I think they can hopefully work together.

By that, I mean I think companies will do clinical trials that will show efficacy for things like recurring UTI infections and CF patients, things where people are infected, but it’s not so immediately life-threatening as it was with, say, Tom. So those things will hopefully provide rigorous clinical data that at least some phages work. Where I think Phage Canada and Phage Australia and other organizations like that will always have a role is because you can’t really do a clinical trial for someone like in Tom’s situation. And I think there’s always gonna be people like that, unfortunately.

My hope would be that governments and people like Jon Iredell at Phage Australia and Greg German at Phage Canada can hopefully get even more support from the government for their centers if clinical trials, admittedly with different phages, show efficacy. This would strengthen the argument that governments should pay for this, even though the phages that are being developed in those countries haven’t had specifically those phages tested in clinical trials. It will be interesting to see how that plays out.

Jessica: What do you think that phage developers or researchers should do more of or do less of from your vantage point? Is there any kind of advice you give when people ask you, or messages that you think need to get out there? What do you like that you’re seeing, and what are you kind of feeling like still isn’t being addressed?

Joe: Well, when I consult with people, some of the advice I give has to do with how you write applications and stuff like that. I would say that one of the things that I always tell people is try to talk to the NIAID program person because they will give you advice as to how your study section is going to react. They probably have been hearing that study section and they know the biases of the study section.

So I think the NIAID program people really do want to help. A lot of the phage companies are really doing well to get to the point where they’re doing what I think are reasonable clinical trials. And I guess the question, the challenge for them is going to be hopefully, well, they’ve planned their business out so that if the trial is successful, they have a reasonable chance of actually making money with the product. I mean, we all know about the company that developed an antibiotic and then went belly up a year or two later, so hopefully that fate won’t meet them.

I think the real challenge, and phage companies can’t do that much about it, they can try to position themselves as well as they can, but it’s a challenge for anyone who’s trying to come up with an antibiotic or a treatment for antibiotic-resistant infections. It’s, I’m not a medical economist, but everything tells me that it’s a really lousy business model. I mean, if someone develops a new cholesterol medicine, someone like me will be taking it hopefully for like 30 years every day. If you develop a new antibiotic, hopefully someone will take it for 10 days and never need it again. You’re not making nearly as much money. Not to mention the fact that with traditional antibiotics, after a few years they become resistant and you can’t use them anymore. So that’s just a challenge on top of the challenge.

Jessica: On the note of study sections, I was going to ask earlier when you mentioned how the program officers know their study section and know the kind of biases they might have. How long are study sections together and working together in one unit? Is it kind of like this study section is a year and that’s the same people, or do they know in advance, at the point of releasing the grant RFA, who the study section is going to be so if you talk to the program officer, you could actually learn about the study section at that point?

Joe: Okay, so I’m not the best person to answer this question. Having said that, for the thing that Kyung Moon was doing now, they will probably set up a study section anew. Because they don’t traditionally have standing study sections that meet regularly that review only phage grants.

So the issues about knowing your study section are more if you’re sending in what’s called an unsolicited R01 where you have an idea and NIAID or whatever institute you’re applying to hasn’t said, “We’re interested in that.” You just think, “Well, I have an infectious disease-related topic. I’m going to send it to NIAID.” In general, there are program officers at NIAID in charge of three or four different pathogens. If you had a Pseudomonas phage cocktail, you would want to talk to the Pseudomonas program officer, and hopefully, he or she would be able to tell you more about the study section.

The one thing I don’t know is sort of inside baseball: if you’re doing an unsolicited R01, how much influence can you and the program officer have in terms of picking your study section? I mainly dealt with NIAID contracts, and that’s the kind of inside baseball thing that I think you should talk to your program officer about.

Jessica: Yeah, yeah. Okay, yeah. Interesting. Well, this has been super enlightening. I don’t know if there’s any things that you were hoping to share or reflect on, looking back on your career?

Joe: Yeah, and again, I qualify that by saying I am definitely not the best person to speak on some of these details. But sort of big picture, I think it’s been an exciting time. Obviously, cases like Tom’s and other cases that have been reported, just from the human side, and I think it affected you too. You hear cases like Mallory Smith where she didn’t get phage fast enough, and it kind of breaks your heart. And you think, well, what can we do? And I imagine that’s part of the reason, in addition to the fact that it was probably fun to live in Australia, that you went to Australia.

Because, you know, a lot of us want to… for the most part, no one wants to see people die unnecessarily. A lot of us believe, and I certainly think that there are very few people who would look seriously at Tom Patterson’s case and not think that he was probably saved by the phages. And certainly, as I always say to my wife, if I’m in that situation, I want you to move heaven and earth to find phages for me.

So obviously, we all want a situation where phages are available in situations where we think they’re going to work. But we’ve discussed a little bit the economic challenges of all of that, which aren’t trivial. We’re trying to balance the need for rigorous clinical trials that will really allow us to understand in the long run, I believe, will make us in a better position to have more successful treatment cases because we’ll understand better how to dose the phages and what factors are likely to be involved in successful and unsuccessful cases.

That’s why we do clinical trials for at least two reasons. One is to show that they work, and the other is to get data as to how you can most optimize the use of whatever therapy you’re using. I wouldn’t advocate just getting a bunch of phages together and putting them into people whenever. Obviously, you want to treat people, but you also want to have cases where we know why they did or didn’t work so that when the future Tom Pattersons of the world, we’ve learned more. I love Chip Schooley, and this isn’t a criticism, but I don’t know if you’ve ever asked Chip how he decided how much phage to give Tom Patterson. It was basically, well, there’s a limit of how much endotoxin someone can get. We added as much as we could without going over the endotoxin limit. I mean, and no one would think, you know, that’s a great way to be doing medicine, you just, at some level you give the maximum tolerable dose and it does or doesn’t work.

I mean, I’m sure Chip’s involved in clinical trials now because if there’s another case like Tom Patterson, he would like to have a little bit more confidence that he’s giving the right dose. I mean, with Tom, he didn’t have time to figure all that stuff out. He had to do something and so he did what seemed to make the most sense. Forgetting the economics, but trying to balance the treating people who are in need while still allowing for us to understand better what the optimal treatment regimens are with phage, is not trivial. And that’s even leaving out all the economic challenges that we discussed ad nauseum earlier. If it was easy, it would be solved.

Jessica: I really, really appreciate this. I think it’s encouraging that the phage field is not seen as this ‘never going to work’ sort of thing, you know, it’s not actually that much of an underdog anymore.

Links

Listen to the conversation on the Podovirus Podcast!

Or watch it on Youtube!